Publications by authors named "Michelle Jankowski"

27 Publications

  • Page 1 of 1

Risk Factors for Pneumothorax Development Following CT-Guided Core Lung Nodule Biopsy.

J Bronchology Interv Pulmonol 2021 Oct 14. Epub 2021 Oct 14.

Oakland University William Beaumont School of Medicine, Rochester Department of Diagnostic Radiology and Molecular Imaging Division of Pulmonary Critical Care, Beaumont Health System, Royal Oak, MI.

Background: This study aims to correlate nodule, patient, and technical risk factors less commonly investigated in the literature with pneumothorax development during computed tomography-guided core needle lung nodule biopsy.

Patients And Methods: Retrospective data on 671 computed tomography-guided percutaneous core needle lung biopsies from 671 patients at a tertiary care center between March 2014 and August 2016. Univariate and multivariable logistic regression analyses were used to identify pneumothorax risk factors.

Results: The overall incidence of pneumothorax was 26.7% (n=179). Risk factors identified on univariate analysis include anterior [odds ratio (OR)=1.98; P<0.001] and lateral (OR=2.17; P=0.002) pleural surface puncture relative to posterior puncture, traversing more than one pleural surface with the biopsy needle (OR=2.35; P=0.06), patient positioning in supine (OR=2.01; P<0.001) and decubitus nodule side up (OR=2.54; P=0.001) orientation relative to decubitus nodule side down positioning, and presence of emphysema in the path of the biopsy needle (OR=3.32; P<0.001). In the multivariable analysis, the presence of emphysematous parenchyma in the path of the biopsy needle was correlated most strongly with increased odds of pneumothorax development (OR=3.03; P=0.0004). Increased body mass index (OR=0.95; P=0.001) and larger nodule width (cm; OR=0.74; P=0.02) were protective factors most strongly correlated with decreased odds of pneumothorax development.

Conclusion: Emphysema in the needle biopsy path is most strongly associated with pneumothorax development. Increases in patient body mass index and width of the target lung nodule are most strongly associated with decreased odds of pneumothorax.
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http://dx.doi.org/10.1097/LBR.0000000000000816DOI Listing
October 2021

Long-term outcome of brachytherapy treatment for coronary in-stent restenosis: Ten-year follow-up.

Catheter Cardiovasc Interv 2019 03 2;93(4):E211-E216. Epub 2018 Oct 2.

Beaumont Hospital Royal Oak, Royal Oak, Michigan.

Objectives: The objective of this study was to determine the long-term major adverse cardiac events (MACE) in patients treated with intracoronary brachytherapy (ICBT) for coronary in-stent restenosis (ISR).

Background: ICBT was commonly used to treat coronary ISR prior to the availability of drug-eluting stents (DES). The long-term outcomes of ICBT for ISR remain unknown.

Methods: Six hundred and eighty consecutive patients who underwent ICBT treated for ISR between September 1998 and April 2005 were included in the study. Clinical and angiographic data were collected and the long-term MACE were measured for all-cause death, myocardial infarction (MI), and target vessel revascularization (TVR) at 10-year follow-up.

Results: Patients were 63 ± 11 years old (66% male). The majority of patients were treated with a bare metal stent 670/680 (99%) prior to ICBT. Significant baseline clinical findings include high incidence of smokers 479/680 (70%), hyperlipidemia 638/680 (94%), and multivessel disease 526/680 (77%). The majority of target lesions were diffuse 407/680 (60%), and either in the left anterior descending 258/680 (38%) or right coronary artery 215/680 (32%). At 10-year follow-up, the rate of death was 25%, MI was 22.4%, and TVR was 48%.

Conclusion: MACE at 10-year follow-up following ICBT for ISR indicates steady rate of death and MI and declining rate of TVR after 5 years.
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http://dx.doi.org/10.1002/ccd.27866DOI Listing
March 2019

Additional treatments, satisfaction, symptoms and quality of life in women 1 year after vaginal and abdominal pelvic organ prolapse repair.

Int Urol Nephrol 2018 Jun 16;50(6):1031-1037. Epub 2018 Mar 16.

Beaumont Health, 3535 W. 13 Mile Road, Room 428, Urology Administration, Royal Oak, MI, 48067, USA.

Objectives: To evaluate additional treatments, symptoms, satisfaction and quality of life 1 year after vaginal and abdominal pelvic organ prolapse (POP) repair.

Methods: Adult women enrolled in a prospective POP database were reviewed. Baseline and outcomes data 1 year after surgery were collected including the Pelvic Floor Distress Inventory (PFDI) and mailed surveys. Data were analyzed with descriptive statistics, Fisher's exact tests and t tests.

Results: Of 222 women, 147 (66%) had vaginal and 75 (34%) had abdominal repair. Vaginal group patients were older (64.1 vs. 59.7 years; p = 0.003), but other demographic characteristics did not differ. Vaginal group patients had lower baseline anterior and apical prolapse grades (anterior 2.7 vs. 3.1, p = 0.003; apical 2.1 vs. 3.1, p < 0.001). Baseline PFDI scores were similar. Scores improved significantly for both groups after 1 year, but 1-year PFDI scores were significantly higher in the vaginal group (45.6 vs. 32.6, p = 0.032). Scores were not different when adjusted for age and prolapse grade (p = 0.24). At 1 year, most patients in the vaginal and abdominal groups reported moderately/markedly improved overall symptoms (72/108 vs. 50/60, p = 0.030) and quality of life (89/101 vs. 54/59, p = 0.601). Most were satisfied with surgery (68/101 vs. 48/59, p = 0.067). Retreatment rates (pelvic floor physical therapy, medications, coping strategies, surgical procedures) were similar (34/109 vs. 15/62, p = 0.381). Vaginal mesh use did not affect additional treatments, patient satisfaction or symptoms.

Conclusions: Although symptoms improve and most women are satisfied with surgery, about one in four women have additional therapy in the first year after POP repair.
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http://dx.doi.org/10.1007/s11255-018-1846-5DOI Listing
June 2018

Methylation in benign prostate and risk of disease progression in men subsequently diagnosed with prostate cancer.

Int J Cancer 2016 Jun 2;138(12):2884-93. Epub 2016 Mar 2.

Department of Environmental Health Sciences, Columbia University, New York, NY.

In DNA from prostate tumors, methylation patterns in gene promoter regions can be a biomarker for disease progression. It remains unclear whether methylation patterns in benign prostate tissue--prior to malignant transformation--may provide similar prognostic information. To determine whether early methylation events predict prostate cancer outcomes, we evaluated histologically benign prostate specimens from 353 men who eventually developed prostate cancer and received "definitive" treatment [radical prostatectomy (58%) or radiation therapy (42%)]. Cases were drawn from a large hospital-based cohort of men with benign prostate biopsy specimens collected between 1990 and 2002. Risk of disease progression associated with methylation was estimated using time-to-event analyses. Average follow-up was over 5 years; biochemical recurrence (BCR) occurred in 91 cases (26%). In White men, methylation of the APC gene was associated with increased risk of BCR, even after adjusting for standard clinical risk factors for prostate cancer progression (adjusted hazard ratio (aHR) = 2.26; 95%CI 1.23-4.16). APC methylation was most strongly associated with a significant increased risk of BCR in White men with low prostate specific antigen at cohort entry (HR = 3.66; 95%CI 1.51-8.85). In additional stratified analyses, we found that methylation of the RARB gene significantly increased risk of BCR in African American cases who demonstrated methylation of at least one of the other four genes under study (HR = 3.80; 95%CI 1.07-13.53). These findings may have implications in the early identification of aggressive prostate cancer as well as reducing unnecessary medical procedures and emotional distress for men who present with markers of indolent disease.
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http://dx.doi.org/10.1002/ijc.30038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878837PMC
June 2016

The Michigan Spine Surgery Improvement Collaborative: a statewide Collaborative Quality Initiative.

Neurosurg Focus 2015 Dec;39(6):E7

Departments of 1 Neurosurgery.

OBJECT Given the scrutiny of spine surgery by policy makers, spine surgeons are motivated to demonstrate and improve outcomes, by determining which patients will and will not benefit from surgery, and to reduce costs, often by reducing complications. Insurers are similarly motivated. In 2013, Blue Cross Blue Shield of Michigan (BCBSM) and Blue Care Network (BCN) established the Michigan Spine Surgery Improvement Collaborative (MSSIC) as a Collaborative Quality Initiative (CQI). MSSIC is one of the newest of 21 other CQIs that have significantly improved-and continue to improve-the quality of patient care throughout the state of Michigan. METHODS MSSIC focuses on lumbar and cervical spine surgery, specifically indications such as stenosis, disk herniation, and degenerative disease. Surgery for tumors, traumatic fractures, deformity, scoliosis, and acute spinal cord injury are currently not within the scope of MSSIC. Starting in 2014, MSSIC consisted of 7 hospitals and in 2015 included another 15 hospitals, for a total of 22 hospitals statewide. A standardized data set is obtained by data abstractors, who are funded by BCBSM/BCN. Variables of interest include indications for surgery, baseline patient-reported outcome measures, and medical history. These are obtained within 30 days of surgery. Outcome instruments used include the EQ-5D general health state score (0 being worst and 100 being the best health one can imagine) and EQ-5D-3 L. For patients undergoing lumbar surgery, a 0 to 10 numeric rating scale for leg and back pain and the Oswestry Disability Index for back pain are collected. For patients undergoing cervical surgery, a 0 to 10 numeric rating scale for arm and neck pain, Neck Disability Index, and the modified Japanese Orthopaedic Association score are collected. Surgical details, postoperative hospital course, and patient-reported outcome measures are collected at 90-day, 1-year, and 2-year intervals. RESULTS As of July 1, 2015, a total of 6397 cases have been entered into the registry. This number reflects 4824 eligible cases with confirmed surgery dates. Of these 4824 eligible cases, 3338 cases went beyond the 120-day window and were considered eligible for the extraction of surgical details, 90-day outcomes, and adverse events. Among these 3338 patients, there are a total of 2469 lumbar cases, 862 cervical cases, and 7 combined procedures that were entered into the registry. CONCLUSIONS In addition to functioning as a registry, MSSIC is also meant to be a platform for quality improvement with the potential for future initiatives and best practices to be implemented statewide in order to improve quality and lower costs. With its current rate of recruitment and expansion, MSSIC will provide a robust platform as a regional prospective registry. Its unique funding model, which is supported by BCBSM/BCN, will help ensure its longevity and viability, as has been observed in other CQIs that have been active for several years.
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http://dx.doi.org/10.3171/2015.10.FOCUS15370DOI Listing
December 2015

Influence of NSAID Use Among Colorectal Cancer Survivors on Cancer Outcomes.

Am J Clin Oncol 2017 Aug;40(4):370-374

*Department of Public Health Sciences, Henry Ford Health System, Detroit, MI †HealthPartners, Minneapolis, MN ‡Department of Epidemiology School of Public Health, Boston University, Boston, MA.

Purpose: Colorectal cancer (CRC) is the third most common cancer diagnosed in men and women in the United States. Given the availability of effective screening, most tumors are found early enough to offer patients substantial long-term survival. Thus there is a resulting significant population of CRC survivors for whom modifiable risk factors for recurrence and survival would be of interest.

Methods: We conducted a population-based retrospective cohort study among patients enrolled in 2 large Midwestern health plans for which claims data, including pharmacy fill data, and medical record data were available. Men and women who were 40 years of age or older at the time of CRC diagnosis with disease less than stage IV and no history of Crohn disease, ulcerative colitis, and irritable bowel syndrome were included. CRC cases diagnosed between January 1, 1990 and December 31, 2000 were included if they met the inclusion criteria. Adjusted Cox proportional hazard models were used with exposure modeled as a time-dependent covariate. We assessed progression-free survival, defined as an aggressive polyp or invasive disease, and overall survival.

Results: After adjustment for age at diagnosis, sex, race, body mass index, stage, side of initial tumor, and tumor histology, we found that current users of nonsteroidal anti-inflammatory drugs had a 3-fold decreased risk of recurrence and a >7-fold decreased risk of death. Our results are statistically significant with P-values <0.05.

Conclusions: Our results suggest that current use of nonsteroidal anti-inflammatory drugs provides significant improvements in CRC outcomes.
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http://dx.doi.org/10.1097/COC.0000000000000164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465051PMC
August 2017

Variable change in renal function by hypertonic saline.

World J Crit Care Med 2014 May 4;3(2):61-7. Epub 2014 May 4.

Jesse J Corry, Panayiotis Varelas, Tamer Abdelhak, Stacey Morris, Marlisa Hawley, Allison Hawkins, Department of Neurology, Henry Ford Hospital, Marshfield, WI 54449, United States.

Aim: To investigate the effects of hypertonic saline in the neurocritical care population.

Methods: We retrospectively reviewed our hospital's use of hypertonic saline (HS) since March of 2005, and prospectively since October 2010. Comparisons were made between admission diagnoses, creatinine change (Cr), and HS formulation (3% NaCl, 3% NaCl/sodium acetate mix, and 23.4% NaCl) to patients receiving normal saline or lactated ringers. The patients (n = 1329) of the retrospective portion were identified. The data presented represents the first 230 patients with data.

Results: Significant differences in Acute Physiology and Chronic Health Evaluation II scores and Glasgow Coma Scale scores occurred between different saline formulations. No significant correlation of Cl(-) or Na(+) with Cr, nor with saline types, occurred. When dichotomized by diagnosis, significant correlations appear. Traumatic brain injury (TBI) patients demonstrated moderate correlation between Na(+) and Cr of 0.45. Stroke patients demonstrated weak correlations between Na(+) and Cr, and Cl(-) and Cr (0.19 for both). Patients receiving HS and not diagnosed with intracerebral hemorrhage, stroke, subarachnoid hemorrhage, or TBI demonstrated a weak but significant correlation between Cl(-) and Cr at 0.29.

Conclusion: Cr directly correlates with Na(+) or Cl(-) in stroke, Na(+) in TBI, and Cl(-) in other populations. Prospective comparison of HS and renal function is needed.
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http://dx.doi.org/10.5492/wjccm.v3.i2.61DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038814PMC
May 2014

Gene-environment interactions between JAZF1 and occupational and household lead exposure in prostate cancer among African American men.

Cancer Causes Control 2014 Jul 7;25(7):869-79. Epub 2014 May 7.

Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA,

Purpose: A single nucleotide polymorphism, rs10486567, in JAZF1 has consistently been associated with increased risk of prostate cancer. The physical interaction of zinc finger proteins, such as JAZF1, with heavy metals may play a role in carcinogenesis. This study assessed potential gene-environment statistical interactions (G×E) between rs10486567 and heavy metals in prostate cancer.

Methods: In a case-only study of 228 African American prostate cancer cases, G×E between rs10486567 and sources of cadmium and lead (Pb) were assessed. Unconditional logistic regression was used to estimate interaction odds ratios (IORs), and generalized estimating equations were used for models containing nested data. Case-control validation of IORs was performed, using 82 controls frequency matched to cases on age-race.

Results: Among cases, a potential G×E interaction was observed between rs10486567 CC genotype and living in a Census tract with a high proportion of housing built before 1950, a proxy for household Pb exposure, when compared to CT or TT carriers (OR 1.81; 95% CI 1.04-3.16; p = 0.036). A stronger G×E interaction was observed when both housing and occupational Pb exposure were taken into account (OR 2.62; 95% CI 1.03-6.68; p = 0.04). Case-control stratified analyses showed the odds of being a CC carrier were higher in cases compared to controls among men living in areas with older housing (OR 2.03; CI 0.99-4.19; p = 0.05) or having high occupational Pb exposure (OR 2.50; CI 1.01-6.18; p = 0.05).

Conclusions: In African American men, the association between JAZF1 rs10486567 and prostate cancer may be modified by exposure to heavy metals such as Pb.
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http://dx.doi.org/10.1007/s10552-014-0387-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267567PMC
July 2014

Case-only gene-environment interaction between ALAD tagSNPs and occupational lead exposure in prostate cancer.

Prostate 2014 May 5;74(6):637-46. Epub 2014 Feb 5.

Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan; Population Studies and Prevention Programs, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan.

Background: Black men have historically had higher blood lead levels than white men in the U.S. and have the highest incidence of prostate cancer in the world. Inorganic lead has been classified as a probable human carcinogen. Lead (Pb) inhibits delta-aminolevulinic acid dehydratase (ALAD), a gene recently implicated in other genitourinary cancers. The ALAD enzyme is involved in the second step of heme biosynthesis and is an endogenous inhibitor of the 26S proteasome, a master system for protein degradation and a current target of cancer therapy.

Methods: Using a case-only study design, we assessed potential gene-environment (G × E) interactions between lifetime occupational Pb exposure and 11 tagSNPs within ALAD in black (N = 260) and white (N = 343) prostate cancer cases.

Results: Two ALAD tagSNPs in high linkage disequilibrium showed significant interaction with high Pb exposure among black cases (rs818684 interaction odds ratio or IOR = 2.73, 95% CI 1.43-5.22, P = 0.002; rs818689 IOR = 2.20, 95% CI 1.15-4.21, P = 0.017) and an additional tagSNP, rs2761016, showed G × E interaction with low Pb exposure (IOR = 2.08, 95% CI 1.13-3.84, P = 0.019). Further, the variant allele of rs818684 was associated with a higher Gleason grade in those with high Pb exposure among both blacks (OR 3.96, 95% CI 1.01-15.46, P = 0.048) and whites (OR 2.95, 95% CI 1.18-7.39, P = 0.020).

Conclusions: Genetic variation in ALAD may modify associations between Pb and prostate cancer. Additional studies of ALAD, Pb, and prostate cancer are warranted and should include black men. Prostate 74:637-646, 2014. © 2014 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/pros.22781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112406PMC
May 2014

Obesity and future prostate cancer risk among men after an initial benign biopsy of the prostate.

Cancer Epidemiol Biomarkers Prev 2013 May 23;22(5):898-904. Epub 2013 Apr 23.

Columbia University, 722 West 168th Street, Rm 714, New York, NY 10032, USA.

Background: In general population studies, obesity has been associated with risk of high-grade prostate cancer, but little is known about obesity and future prostate cancer risk among men with an initial benign biopsy of the prostate; a high-risk population.

Methods: Within a cohort of 6,692 men followed up after a biopsy or transurethral resection of the prostate (TURP) with benign findings, a nested case-control study was conducted of 494 prostate cancer cases and controls matched on age, race, follow-up duration, biopsy versus TURP and date of procedure. Body mass index at the time of the initial procedure was abstracted from medical records, and initial biopsy specimens were reviewed for the presence of prostatic intraepithelial neoplasia (PIN).

Results: Obesity was associated with the presence of PIN in the initial benign specimen [OR = 2.15; 95% confidence interval (CI) 1.13-4.11]. After adjustment for the matching variables, family history of prostate cancer, prostate-specific antigen (PSA) levels at the initial procedure, the number of PSA tests and digital rectal examinations during follow-up, obesity (OR = 1.57; 95% CI, 1.07-2.30) at the time of the initial procedure was associated with prostate cancer incidence during follow-up. Risk associated with obesity was confined to cases with follow-up less than 1,538 days, the median duration of follow-up among cases (OR = 1.95; 95% CI, 1.09-3.48).

Conclusions: Obesity is associated with the presence of PIN in benign specimens and with future prostate cancer risk after an initial benign finding.

Impact: Obesity may be a factor to consider when planning clinical follow-up after a benign biopsy.
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http://dx.doi.org/10.1158/1055-9965.EPI-12-0965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696983PMC
May 2013

Urine toxicology screening in an urban stroke and TIA population.

Neurology 2013 Apr 17;80(18):1702-9. Epub 2013 Apr 17.

Department of Neurology, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA.

Objective: We sought to determine the rate of urine toxicology screening, differences in testing, and outcomes among patients with stroke and TIA presenting to a tertiary care emergency department.

Methods: In this retrospective cohort study, patients admitted with stroke or TIA to a single tertiary care stroke center between June 2005 and January 2007 were identified through a stroke database. Factors that predicted urine toxicology screening of patients and a positive test, and discharge outcomes of patients based on toxicology result were analyzed. Stroke severity, treatment with tissue plasminogen activator, discharge status, and stroke etiology were compared between toxicology positive and negative patients.

Results: A total of 1,024 patients were identified: 704 with ischemic stroke, 133 with intracerebral hemorrhage, and 205 with TIA. Urine toxicology screening was performed in 420 patients (40%); 11% of these studies were positive for cocaine (19% younger than 50 years and 9% 50 years or older). Factors that significantly predicted the performance of a urine toxicology screen were younger age (<50 years) and black race (<0.001). Positive toxicology screens occurred in a broad range of patients. There were no significant differences in admission NIH Stroke Scale score, stroke etiology, and discharge status between toxicology-positive and -negative patients.

Conclusions: In this study, patients with stroke and TIA who were young and black were more likely to have urine toxicology screening. Eleven percent of all tested patients (and 9% of patients 50 years or older) were positive for cocaine. To avoid disparities, we suggest that all stroke and TIA patients be tested.
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http://dx.doi.org/10.1212/WNL.0b013e318293e2feDOI Listing
April 2013

Methylation of the RARB gene increases prostate cancer risk in black Americans.

J Urol 2013 Jul 30;190(1):317-24. Epub 2013 Jan 30.

Department of Environmental Health Sciences, Columbia University, New York, New York, USA.

Purpose: Gene promoter hypermethylation may be useful as a biomarker for cancer risk in histopathologically benign prostate specimens.

Materials And Methods: We performed a nested case-control study of gene promoter methylation status for 5 genes (APC, RARB, CCND2, RASSF1 and MGMT) measured in benign biopsy specimens from 511 prostate cancer case-control pairs. We estimated the overall and race stratified risk of subsequent prostate cancer associated with methylation status.

Results: On race stratified analysis RARB methylation was associated with a higher cancer risk in black American men (OR 2.18, 95% CI 1.39-3.44). APC methylation was associated with an increased risk of high grade tumors (OR 2.43, 95% CI 1.20-4.90), which was higher in black than in white men (OR 3.21 vs 2.04). In cases RARB and APC gene methylation in benign prostate samples persisted in matched malignant specimens. In black cases the combined risk associated with RARB and APC methylation (OR 3.04, 95% CI 1.44-6.42) was greater than the individual risk of each gene and significantly different from that in white cases (OR 1.14, 95% CI 0.56-2.30).

Conclusions: RARB gene methylation in histopathologically benign prostate samples was associated with a statistically significant increased risk of subsequent prostate cancer in black men. Methylation data on additional genes may improve risk stratification and clinical decision making algorithms for cancer screening and diagnosis.
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http://dx.doi.org/10.1016/j.juro.2013.01.083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779133PMC
July 2013

A prospective study of socioeconomic status, prostate cancer screening and incidence among men at high risk for prostate cancer.

Cancer Causes Control 2013 Feb 8;24(2):297-303. Epub 2012 Dec 8.

Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, NY 10032, USA.

Purpose: Higher socioeconomic status (SES) men are at higher risk of prostate cancer (PCa) diagnosis, an association commonly interpreted as a function of higher rates of prostate screening among higher SES men. However, the extent to which screening explains this association has not been well quantified.

Methods: Within a Detroit area cohort of 6,692 men followed up after a benign prostate procedure, a case-control study was conducted of 494 PCa cases and controls matched on age, race, duration of follow-up, and date of initial benign finding; 2000 Census data were used in a principal component analysis to derive a single factor, labeled the neighborhood SES index (NSESI), representing zip code-level SES.

Results: Among cases, higher SES was associated with a younger age at initial biopsy: -1.48 years (95 % CI, -2.32, -0.64) per unit NSESI. After adjustment for confounders and duration of follow-up, higher SES was associated with more PSA tests and DRE during follow-up; 9 % (95 % CI, 2, 16) and 8 % (95 % CI, 1, 15) more respectively, per unit NSESI. Higher SES was associated with a higher risk of PCa diagnosis during follow-up, multivariable adjusted OR = 1.26 per unit increase in NSESI (95 % CI, 1.04, 1.49). Further adjustment for screening frequency somewhat reduced the association between SES and PCa risk (OR = 1.19 per unit NSESI, 95 % CI, 0.98, 1.44).

Conclusions: Differences in screening frequency only partially explained the association between higher zip code SES and PCa risk; other health care-related factors should also be considered as explanatory factors.
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http://dx.doi.org/10.1007/s10552-012-0108-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557724PMC
February 2013

Elevated polycyclic aromatic hydrocarbon-DNA adducts in benign prostate and risk of prostate cancer in African Americans.

Carcinogenesis 2013 Jan 12;34(1):113-20. Epub 2012 Oct 12.

Department of Environmental Health Sciences, Columbia University, New York, NY, USA.

Carcinogen-DNA adducts, a marker of DNA damage, are capable of inducing mutations in oncogenes and tumor suppressor genes, resulting in carcinogenesis. We have shown previously that polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels in prostate cancer cases vary by cellular histology and that higher adduct levels are associated with biochemical recurrence. A nested case-control study was conducted in a historical cohort of 6692 men with histopathologically benign prostate specimens. PAH-DNA adduct levels were determined by immunohistochemistry in benign prostate specimens from 536 prostate cancer case-control pairs (59% White and 41% African American). We estimated the overall and race-stratified risk of subsequent prostate cancer associated with higher adduct levels. Prostate cancer risk for men with elevated adduct levels (defined as greater than control group median) was slightly increased [odds ratio (OR) = 1.28, 95% confidence interval (CI) = 0.98-1.67, P = 0.07]. After race stratification, elevated adduct levels were significantly associated with increased risk in African American men (OR = 1.56, CI = 1.00-2.44, *P = 0.05) but not White men (OR = 1.14, CI = 0.82-1.59, P = 0.45). Elevated PAH-DNA adduct levels were significantly associated with 60% increased risk of prostate cancer among cases diagnosed 1-4 years after cohort entry (OR = 1.60, CI = 1.07-2.41) with a greater risk observed in African Americans within the first 4 years of follow-up (OR = 4.71, CI = 1.97-11.26, ***P = 0.0005). Analyses stratified by age or tumor grade revealed no additional significant heterogeneity in risk. Increased prostate cancer risk associated with high PAH-DNA adduct levels in benign prostate was found only in African Americans; risk was greatest within 4 years of follow-up, possibly reflecting a carcinogenic process not yet histologically detectable.
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http://dx.doi.org/10.1093/carcin/bgs326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534199PMC
January 2013

Inflammation and preneoplastic lesions in benign prostate as risk factors for prostate cancer.

Mod Pathol 2012 Jul 30;25(7):1023-32. Epub 2012 Mar 30.

Department of Pathology, Henry Ford Hospital, Detroit, MI, USA.

Benign changes ranging from atrophy and inflammation to high-grade prostatic intraepithelial neoplasia (HGPIN) are common findings on prostate core needle biopsies. Although atrophy and inflammation may be precursors of prostate cancer, only HGPIN is currently recommended to be included in surgical pathology reports. To determine whether these benign findings increase prostate cancer risk, we conducted a case-control study nested within a historical cohort of 6692 men with a benign prostate specimen collected between 1990 and 2002. The analytic sample included 574 case-control pairs comprised of cases diagnosed with prostate cancer a minimum of 1 year after cohort entry and controls matched to cases on date and age at cohort entry, race, and type of specimen. The initial benign specimen was reviewed for presence of HGPIN, atrophy (simple, lobular, and partial) and inflammation (glandular and/or stromal). HGPIN significantly increased risk for prostate cancer (odds ratio (OR)=2.00; 95% confidence interval (CI)=1.25-3.20). Inflammation within the stromal compartment was associated with decreased risk (OR=0.66; CI=0.52-0.84), and diffuse stromal inflammation of severe grade had the strongest inverse association with risk (OR=0.21; CI=0.07-0.62). In a model adjusted for prostate-specific antigen (PSA) level at cohort entry and inflammation, simple atrophy was associated with a 33% increased prostate cancer risk that was marginally significant (P=0.03). Clinicians should consider patterns and extent of inflammation when managing high-risk patients with negative biopsy results. Identifying benign inflammatory processes that underlie high PSA levels would help to reduce the number of unnecessary repeated prostate biopsies.
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http://dx.doi.org/10.1038/modpathol.2012.51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589982PMC
July 2012

Deletion of the SPARC acidic domain or EGF-like module reduces SPARC-induced migration and signaling through p38 MAPK/HSP27 in glioma.

Carcinogenesis 2012 Feb 23;33(2):275-84. Epub 2011 Nov 23.

Hermelin Brain Tumor Center, Department of Neurosurgery, Henry Ford Hospital, Detroit, MI 48202, USA.

We previously demonstrated that secreted protein acidic and rich in cysteine (SPARC) increases heat shock protein 27 (HSP27) expression and phosphorylation and promotes glioma cell migration through the p38 mitogen-activated protein kinase (MAPK)/HSP27 signaling pathway. As different regions of the SPARC protein mediate different SPARC functions, elucidating which SPARC domains regulate HSP27 expression, signaling and migration might provide potential therapeutic strategies to target these functions. To investigate the roles of specific domains, we used an SPARC-green fluorescent protein (GFP) fusion protein and constructs of SPARC-GFP with deletions of either the acidic domain (ΔAcidic) or the epidermal growth factor (EGF)-like module (ΔEGF). GFP, SPARC-GFP and the two deletion mutants were expressed in U87MG glioma cells. Characterization of the derived stable clones by confocal imaging and western blotting suggests proper folding, processing and secretion of the deletion constructs. Uptake of the constructs by naive cells suggests enhanced internalization of ΔAcidic and reduced internalization of ΔEGF. Wound and transwell migration assays and western blot analysis confirm our previous results and indicate that ΔAcidic reduces SPARC-induced migration and p38 MAPK/HSP27 signaling and ΔEGF decreases SPARC-induced migration and dramatically decreases the expression and phosphorylation of HSP27 but is poorly internalized. Loss of the EGF-like module suppresses the enhanced HSP27 protein stability conferred by SPARC. In conclusion, deletions of the acidic domain and EGF-like module have differential effects on cell surface binding and HSP27 protein stability; however, both regions regulate SPARC-induced migration and signaling through HSP27. Our data link the domains of SPARC with different functions and suggest one or both of the constructs as potential therapeutic agents to inhibit SPARC-induced migration.
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http://dx.doi.org/10.1093/carcin/bgr276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3271264PMC
February 2012

The Metabolic Syndrome and Biochemical Recurrence following Radical Prostatectomy.

Prostate Cancer 2011 25;2011:245642. Epub 2011 Sep 25.

Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.

Metabolic syndrome refers to a set of conditions that increases the risk of cardiovascular disease and has been associated with an increased risk of prostate cancer, particularly among African American men. This study aimed to estimate the association of metabolic syndrome with biochemical recurrence (BCR) in a racially diverse population. Among 383 radical prostatectomy patients, 67 patients had documented biochemical recurrence. Hypertension was significantly, positively associated with the rate of BCR (hazard ratio (HR) = 2.1; 95%  CI = 1.1, 3.8). There were distinct racial differences in the prevalence of individual metabolic syndrome components; however, the observed associations with BCR did not differ appreciably by race. We conclude that hypertension may contribute to a poorer prognosis in surgically treated prostate cancer patients. Our findings suggest that targeting components of the metabolic syndrome which are potentially modifiable through lifestyle interventions may be a viable strategy to reduce risk of BCR in prostate cancer.
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http://dx.doi.org/10.1155/2011/245642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196931PMC
November 2011

Red wine consumption is inversely associated with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-DNA adduct levels in prostate.

Cancer Prev Res (Phila) 2011 Oct 16;4(10):1636-44. Epub 2011 Aug 16.

Department of Public Health Sciences, Henry Ford Health System, Detroit, MI 48202, USA.

In humans, genetic variation and dietary factors may alter the biological effects of exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), one of the major heterocyclic amines generated from cooking meats at high temperatures that has carcinogenic potential through the formation of DNA adducts. Previously, we reported grilled red meat consumption associated with PhIP-DNA adduct levels in human prostate. In this study, we expanded our investigation to estimate the associations between beverage consumption and PhIP-DNA adduct levels in prostate for 391 prostate cancer cases. Of the 15 beverages analyzed, red wine consumption had the strongest association with PhIP-DNA adduct levels showing an inverse correlation in both tumor (P = 0.006) and nontumor (P = 0.002) prostate cells. Red wine consumption was significantly lower in African American compared with white cases, but PhIP-DNA adduct levels in prostate did not vary by race. In African Americans compared with whites, however, associations between red wine consumption and PhIP-DNA adduct levels were not as strong as associations with specific (e.g., SULT1A1 and UGT1A10 genotypes) and nonspecific (e.g., African ancestry) genetic variation. In a multivariable model, the covariate for red wine consumption explained a comparable percentage (13%-16%) of the variation in PhIP-DNA adduct levels in prostate across the two racial groups, but the aforementioned genetic factors explained 33% of the PhIP-DNA adduct variation in African American cases, whereas only 19% of the PhIP-DNA adduct variation in whites. We conclude that red wine consumption may counteract biological effects of PhIP exposure in human prostate, but genetic factors may play an even larger role, particularly in African Americans.
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http://dx.doi.org/10.1158/1940-6207.CAPR-11-0100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188357PMC
October 2011

Polymorphisms in glutathione S-transferase genes increase risk of prostate cancer biochemical recurrence differentially by ethnicity and disease severity.

Cancer Causes Control 2009 Dec;20(10):1915-26

Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.

Objective: Genetic polymorphisms that modify the detoxifying activity of glutathione S-transferases (GSTs) can affect the level of carcinogenic metabolites created by endogenous steroid hormones and exogenous chemical substances. Although the GSTM1 null genotype has been shown to increase prostate cancer mortality in Caucasians, potential associations between GST polymorphisms and prostate cancer biochemical recurrence (BCR) have not been well studied, particularly in African-Americans.

Methods: We examined potential associations between the GSTM1 null, GSTT1 null and GSTP1 Ile105Val polymorphisms and BCR, after prostatectomy, in 168 African-American and 226 Caucasian patients treated at Henry Ford Hospital in Detroit, Michigan using Cox proportional hazards modeling.

Results: We found that African-Americans with the GSTT1 null genotype had increased BCR risk compared to those having GSTT1 present (hazard ratio (HR) = 2.30; 95% CI = 1.01–5.18; p = 0.04); and African-Americans with the GSTT1 null genotype and high grade tumors had an even greater risk (HR = 7.82; 95% CI = 2.49–24.50; p < 0.001). In Caucasians, an increased risk was observed in those patients with high grade tumors and the GSTM1 null genotype (HR = 2.88; 95% CI = 1.16–7.14; p = 0.02). Similar associations were observed for advanced stage and more aggressive (high grade or advanced stage) disease.

Conclusion: Our results suggest GSTs may hold promise as therapeutic targets in more advanced prostate cancers, particularly, in African-Americans.
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http://dx.doi.org/10.1007/s10552-009-9385-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777237PMC
December 2009

Racial differences in risk of prostate cancer associated with metabolic syndrome.

Urology 2009 Jul 9;74(1):185-90. Epub 2009 May 9.

Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michiga 48201-1379, USA.

Objectives: To perform a case-control study to test the association between metabolic syndrome features and prostate cancer. The metabolic syndrome refers to a cluster of conditions serving as risk factors for cardiovascular disease. The metabolic syndrome is prevalent in the United States, and the spectrum of specific features has been shown to differ by race and ethnicity. A number of recent reports have linked metabolic syndrome to prostate cancer; however, most studies have not had racially diverse populations to explore differences in risk.

Methods: A case-control study was conducted to test the association between metabolic syndrome features and prostate cancer among 637 patients and 244 controls, with African-American men constituting 43% of the study population.

Results: Metabolic syndrome, defined using a modified version of the Adult Treatment Panel III criteria, was marginally associated with an increased risk of prostate cancer in African-American men (odds ratio [OR] 1.71, 95% confidence interval [CI] 0.97-3.01), but not in white men (OR 1.02, 95% CI 0.64-1.62). After stratifying the patients by stage at diagnosis, African-American men with organ-confined disease were more likely to have a history of metabolic syndrome than were the controls (OR 1.82; 95% CI 1.02-3.23), but no association was observed among those with advanced-stage disease (OR 0.93; 95% CI 0.31-2.77). When evaluating the specific features of the metabolic syndrome, obesity was inversely related to prostate cancer among white men (OR 0.51, 95% CI 0.33-0.80) but unrelated to risk among African-American men (OR 1.15, 95% CI 0.70-1.89).

Conclusions: In the present investigation, the metabolic syndrome was associated with prostate cancer risk in African-American men, but not in white men. The prevalence of this syndrome, coupled with the racial disparity in prostate cancer incidence and outcomes after diagnosis, warrant additional investigation.
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http://dx.doi.org/10.1016/j.urology.2009.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704922PMC
July 2009

Hair grooming practices and central centrifugal cicatricial alopecia.

J Am Acad Dermatol 2009 Apr;60(4):574-8

Multicultural Dermatology Center, Department of Dermatology, Henry Ford Hospital, Detroit, Michigan 48202, USA.

Background: The cause of central centrifugal cicatricial alopecia (CCCA) in African American women remains to be elucidated.

Objective: This study was designed to determine the hair-grooming practices in African American women with and without CCCA and to evaluate possible etiologic factors.

Methods: Utilizing a novel survey instrument, the Hair Grooming Assessment Survey, we performed a retrospective comparative survey of the hair-grooming practices of two populations of African American women seen and evaluated at the Department of Dermatology, Henry Ford Hospital in Detroit, MI, between 2000 and 2007. The case group were women with clinical and histologic diagnosis of CCCA, and the control group were those without a history of alopecia.

Results: All 101 surveys that were returned were analyzed (51 from the case group and 50 from the control group). A strong association was found between the use of both sewn-in hair weaving and cornrow or braided hairstyles with artificial hair extensions and CCCA (P < .04, P < .03, respectively). Similarly, women with CCCA were more likely to report a history of "damage", typically defined as uncomfortable pulling and tenderness, from both sewn-in and glued-in weaves, and from cornrow or braided hairstyles with artificial hair extensions (P < .001, P < .02, and P < .03, respectively). In contrast to previous anecdotal beliefs, no correlation was found between the use of either hot combing or hair relaxers and the development of CCCA.

Limitations: Results are limited by patient recall of past hair grooming practices. Also, as hair grooming practices may vary by geographic region, these results may not be generalized to all women of African descent.

Conclusion: There is a clear difference in both quantitative and qualitative hair grooming practices among African American women with CCCA.
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http://dx.doi.org/10.1016/j.jaad.2008.10.064DOI Listing
April 2009

Predictors and outcomes associated with gastrointestinal bleeding in patients with acute coronary syndromes.

J Thromb Thrombolysis 2007 Feb;23(1):51-5

Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202, USA.

Background: Potent antiplatelet and anticoagulant agents along with early revascularization are increasingly used in patients hospitalized with acute coronary syndromes (ACS). An important complication associated with these therapies is gastrointestinal bleeding (GIB); yet, the predictors, optimal management, and outcomes associated with GIB in ACS patients are poorly studied.

Methods: We investigated the incidence, predictors, pathological findings, and clinical outcomes associated with GIB in patients with ACS hospitalized at a United States tertiary center between 1996 and 2001.

Results: Three percent (80/3,045) of ACS patients developed clinically significant GIB. Predictors of GIB were older age, female gender, non-smoking status, peak troponin I, and prior heart failure, diabetes, or hypertension. Patients with GIB were more critically ill with lower blood pressure and higher heart rates. GIB was associated with an increased need for transfusion, mechanical ventilation, and inotropes/pressors. In-hospital mortality was significantly higher in ACS patients with versus without GIB (36% vs. 5%, P < 0.001). Thirty patients (38%) with GIB underwent endoscopy with no procedural complications of death, arrhythmia, urgent ischemia, or hemodynamic deterioration.

Conclusion: In patients with ACS, GIB is associated with older age, female sex, peak troponin I, non-smoking status, diabetes, hypertension, and heart failure. Hospital mortality is increased eightfold when ACS patients experience GIB. More studies are needed to establish the safety of and optimal timing of endoscopy in these patients.
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http://dx.doi.org/10.1007/s11239-006-9005-8DOI Listing
February 2007

Racial and age differences in colon examination surveillance following a diagnosis of colorectal cancer.

J Natl Cancer Inst Monogr 2005 (35):96-101

HealthPartners Research Foundation, P.O. Box 1524, MS21111R, Minneapolis, MN 55440-1524, USA.

Purpose: The purpose of this analysis is to describe factors associated with colorectal surveillance following diagnosis and treatment of nonmetastatic colorectal cancer.

Methods: Subjects were identified as part of the HMO Cancer Research Network's study of colorectal cancer survivors. To be eligible for the main study, patients had to be part of the staff model components of health maintenance organizations in southeastern Michigan and Minnesota. Using computerized databases, individuals were identified who were 40 years or older with incident nonmetastatic colorectal cancer diagnosed between January 1, 1990, and December 31, 2000. Using data current through 2002, we analyzed the cohort using chi-square test statistics, life tables, and Cox proportional hazards models to understand variations in posttreatment surveillance practices. Subjects were followed up from date of diagnosis to date of recurrence, death, disenrollment from the health plan, or loss to follow-up, which ever came first. We assessed factors associated with colorectal surveillance at 1, 3, and 5 years after treatment. We also included an analysis comparing those who received an exam and those who didn't regardless of exam timing.

Results: A total of 908 patients were eligible for the main study. Of these, we excluded subjects who were not white or African American (n = 27), resulting in an analytic sample of 881 (97% of the eligible cohort). Twenty-five percent of subjects were African American, 43% were female, and 48% were aged 70 years or older. The proportion who received an exam at 1 year was 18%, at 3 years was 60%, and at 5 years was 67%. Chi-square tests showed that African Americans were statistically significantly less likely than whites to receive an exam at all three time points. The Cox proportional hazards model for examinations regardless of timing and adjusted for confounders showed that African Americans were still less likely than whites to receive an exam (hazard ratio = 0.62; 95% confidence interval [CI] = 0.51 to 0.75). The same trend in undersurveillance was also observed for those 80 years of age or older at diagnosis, with an adjusted hazard ratio of 0.39 (95% CI = 0.26 to 0.57).

Conclusion: Our data indicate that colorectal cancer survivors who are African American or aged 80 years or more at diagnosis are less likely to receive posttreatment colorectal surveillance. Whether these differences are due to system or patient level barriers needs further study.
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http://dx.doi.org/10.1093/jncimonographs/lgi045DOI Listing
January 2006

Relation of chronic and acute glycemic control on mortality in acute myocardial infarction with diabetes mellitus.

Am J Cardiol 2005 Jul;96(2):183-6

National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Acute hyperglycemia during myocardial infarction predicts adverse short-term outcomes and mortality in diabetic patients. Conversely, chronic hyperglycemia is associated with an increased incidence of long-term cardiovascular complications, although its effect on acute hyperglycemic response and mortality after acute myocardial infarction is unknown. We investigated the prognostic relation of the glucose concentration at admission and the baseline average glycohemoglobin on acute myocardial infarction mortality. Of 808 consecutive diabetic patients with acute myocardial infarction, the most significant independent predictor of in-hospital mortality was the glucose concentration at admission. Baseline glycohemoglobin strongly correlated with admission hyperglycemia but did not predict mortality independently.
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http://dx.doi.org/10.1016/j.amjcard.2005.03.040DOI Listing
July 2005

Design of a case management approach to enhance cancer screening trial retention among older African American men.

J Aging Health 2004 Nov;16(5 Suppl):39S-57S

Department of Medicine and Section of Health Services Research, Baylor College of Medicine, Veterans Affairs Medical Center (152), 2002 Holcombe Boulevard, Houston, TX 77030, USA.

Purpose: The purpose of this study was to enhance retention among African American men enrolled in a cancer screening trial.

Design: A telephone-based, randomized trial design was used. The intervention group included 352 African American men aged 55+. Case managers contacted participants at least monthly and provided information and referral services to participants and their relatives.

Results: The mean age of participants was 65.7 years. A total of 14,978 calls were made resulting in 780 referrals. The 10 most frequent referrals were for scheduling medical appointments, health information, insurance information, legal aid, transportation, cancer screening information, information technology/computer information, employment, housekeeping/chore services, and food programs.

Conclusions: The case managers served as links between participants and community-based resources. The types of referrals made could be associated with the age-related needs of the participants.
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http://dx.doi.org/10.1177/0898264304268148DOI Listing
November 2004

Meningiomas: loss of heterozygosity on chromosome 10 and marker-specific correlations with grade, recurrence, and survival.

Clin Cancer Res 2003 Oct;9(12):4443-51

Hermelin Brain Tumor Center, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA.

Purpose: In a study of 208 meningiomas, we found a high incidence of loss of heterozygosity (LOH) on chromosome 10 in benign (73.4%), atypical (80.0%), and malignant (86.7%) tumors. A large percentage of the benign and atypical tumors and an increasing percentage of malignant tumors had LOH on multiple loci (43.9%, 45%, and 66.7%, respectively). The high incidence of LOH occurring early in meningioma progression suggests that LOH at individual alleles may serve as a marker of clinically relevant alterations useful for patient diagnosis, the subclassification of tumors, and/or the treatment of patients.

Experimental Design: To test this, we examined 208 sporadic and recurrent meningiomas of all grades for correlations between LOH at 11 markers on chromosome 10 and tumor location, histology, and grade and patient race, gender, age, recurrence, and survival.

Results: Several significant correlations were found. The data indicate that genetic differences occur not only between tumors of different grade, but also between tumors of the same grade, and therefore may be useful to define genetic subsets with clinical implications. LOH at D10S179 (P = 0.001) or D10S169 (P = 0.004) is most likely present in higher-grade meningiomas and, when present in benign tumors, may signify sampling error or a morphologically benign but biologically aggressive tumor. Furthermore, LOH at D10S209 (P = 0.06) and D10S169 (P = 0.01) may predict shorter survival and/or higher rates of recurrence, respectively, in tumors with benign or malignant histology.

Conclusions: We conclude that these chromosome 10 markers deserve further testing as unfavorable prognostic indicators for meningioma patients.
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October 2003

NAD(P)H oxidase mediates angiotensin II-induced vascular macrophage infiltration and medial hypertrophy.

Arterioscler Thromb Vasc Biol 2003 May 13;23(5):776-82. Epub 2003 Mar 13.

Hypertension and Vascular Research Division and the Biostatistics Department, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, Mich 48202-2689, USA.

Objective: Our preliminary data suggested that angiotensin II (Ang II)-induced reactive oxygen species are involved in intercellular adhesion molecule-1 (ICAM-1) expression and leukocyte infiltration in the rat thoracic aorta. Other reports demonstrating reactive oxygen species-induced cell growth suggested a potential role of NAD(P)H oxidase in vascular hypertrophy. In the present study, we postulate that NAD(P)H oxidase is functionally involved in Ang II-induced ICAM-1 expression, macrophage infiltration, and vascular growth, and that oxidase inhibition attenuates these processes independently of a reduction in blood pressure.

Methods And Results: Rats were infused subcutaneously with vehicle or Ang II (750 microg/kg per day) for 1 week in the presence or absence of gp91 docking sequence (gp91ds)-tat peptide (1 mg/kg per day), a cell-permeant inhibitor of NAD(P)H oxidase. Immunohistochemical staining for ICAM-1 and ED1, a marker of monocytes and macrophages, showed that both were markedly increased with Ang II compared with vehicle and were reduced in rats receiving Ang II plus gp91ds-tat. This effect was accompanied by an Ang II-induced increase in medial hypertrophy that was attenuated by coinfusion of gp91ds-tat; however, gp91ds-tat had no effect on blood pressure.

Conclusions: Ang II-enhanced NAD(P)H oxidase plays a role in the induction of ICAM-1 expression, leukocyte infiltration, and vascular hypertrophy, acting independently of changes in blood pressure.
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http://dx.doi.org/10.1161/01.ATV.0000066684.37829.16DOI Listing
May 2003
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