Search

Purpose: Inflammation and neovascularization in vulnerable atherosclerotic plaques are key features for severe clinical events. Dynamic contrast-enhanced (DCE) MRI and FDG PET are two noninvasive imaging techniques capable of quantifying plaque neovascularization and inflammatory infiltrate, respectively. However, their mutual role in defining plaque vulnerability and their possible overlap has not been thoroughly investigated. We studied the relationship between DCE-MRI and (18)F-FDG PET data from the carotid arteries of 40 subjects with coronary heart disease (CHD) or CHD risk equivalent, as a substudy of the dal-PLAQUE trial (NCT00655473)., Methods: The dal-PLAQUE trial was a multicenter study that evaluated dalcetrapib, a cholesteryl ester transfer protein modulator. Subjects underwent anatomical MRI, DCE-MRI and (18)F-FDG PET. Only baseline imaging and biomarker data (before randomization) from dal-PLAQUE were used as part of this substudy. Our primary goal was to evaluate the relationship between DCE-MRI and (18)F-FDG PET data. As secondary endpoints, we evaluated the relationship between (a) PET data and whole-vessel anatomical MRI data, and (b) DCE-MRI and matching anatomical MRI data. All correlations were estimated using a mixed linear model., Results: We found a significant inverse relationship between several perfusion indices by DCE-MRI and (18)F-FDG uptake by PET. Regarding our secondary endpoints, there was a significant relationship between plaque burden measured by anatomical MRI with several perfusion indices by DCE-MRI and (18)F-FDG uptake by PET. No relationship was found between plaque composition by anatomical MRI and DCE-MRI or (18)F-FDG PET metrics., Conclusion: In this study we observed a significant, weak inverse relationship between inflammation measured as (18)F-FDG uptake by PET and plaque perfusion by DCE-MRI. Our findings suggest that there may be a complex relationship between plaque inflammation and microvascularization during the different stages of plaque development. (18)F-FDG PET and DCE-MRI may have complementary roles in future clinical practice in identifying subjects at high risk of cardiovascular events.

Purpose: The incidental detection of early-stage kidney tumors is increasing in the United States. Nephron-sparing approaches (NS) to managing these tumors are equivalent to radical nephrectomy (RN) in oncologic outcomes and have a decreased impact on renal function. Our objective was to evaluate trends in the use of NS over the past decade and the socioeconomic factors associated with its use., Methods: The National Cancer Database was queried to identify patients with stage I kidney cancer between 2000 and 2008. Patients were classified by the type of surgery as NS (local destruction and local excision) or RN. Patients were further categorized by age, race, insurance status, and income. Log-binomial regression was used to estimate prevalence ratios (PR) for the proportion of NS to RN according to demographic and socioeconomic characteristics., Results: From 2000 to 2008, there were 142,194 cases of kidney cancer reported to the NCDB. In these cases, 43,034 (30.3 %) patients had NS, and 86,431 (60.78 %) patients had RN. The prevalence of NS increased 10 % per year (PR = 1.10, p < 0.0001)-from 20.0 % in 2000 to 45.1 % in 2008. Older age, lower income, Black race, Hispanic ethnicity, and lack of health insurance were associated with a decreased prevalence of NS., Conclusions: NS as a treatment for stage I kidney cancer has increased steadily since 2000. Age, racial, and socioeconomic differences may exist in the utilization of NS. Additional analyses, with patient level data, are required to address the independent significance of these variables in an effort to develop strategies to mitigate these potential disparities.

Background: Although urothelial cancer is more common in men, women with urothelial cancer have inferior survival outcomes. The potential existence of gender-related disparities in patients with metastatic urothelial cancer has not been extensively explored., Patients and Methods: Individual patient data were pooled from 8 phase II and phase III trials evaluating first-line cisplatin-based combination chemotherapy in patients with metastatic urothelial carcinoma. Adverse events, treatment delivery, response proportions, and survival outcomes were compared between male and female patients., Results: Of the 543 patients included in the analysis, 100 patients (18%) were women. There was no significant difference in the number of cycles of chemotherapy administered or in the proportions of patients experiencing severe toxicities when comparing male and female patients. There was no difference in the survival distributions between male and female patients (P = .08); the median survival of male patients was 11.7 months (95% confidence interval [CI], 10.5-13.2) compared with 16.2 months for female patients (95% CI, 12.8-20.4). There was no significant difference in survival between men and women when controlling for baseline performance status and/or the presence of visceral metastases., Conclusion: Female patients with metastatic urothelial cancer tolerate cisplatin-based chemotherapy similarly to male patients and achieve comparable clinical outcomes. Although gender-associated survival disparities in patients with metastatic urothelial cancer cannot be completely ruled out, if such disparities exist, they are unlikely related to tolerability or efficacy of chemotherapy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Use of progression-free survival (PFS) as a clinical trial endpoint in first-line treatment of patients with metastatic urothelial carcinoma (UC) is attractive, but would be enhanced by establishing a correlation between PFS and overall survival (OS)., Methods: Data was pooled from 7 phase 2 and 3 trials evaluating cisplatin-based chemotherapy in metastatic UC. An independent cohort of patients enrolled on a phase 3 trial was used for external validation. Landmark analyses for progression at 6 and 9 months after treatment initiation were performed to minimize lead-time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS., Results: A total of 364 patients were included in the initial cohort. The median PFS was 8.21 months (95% confidence interval = 7.43, 8.39) and the median OS was 13.50 months (95% confidence interval = 11.80, 15.67). In the landmark analysis, the median OS for patients who progressed at 6 months was 3.87 months compared with 15.06 months for those patients who did not progress (P < .0001) and the median OS for patients who progressed at 9 months was 5.65 months compared with 21.39 months for those patients who did not progress (P < .0001). A Fleischer model demonstrated a statistically significant dependent correlation between PFS and OS. The findings were externally validated in an independent cohort., Conclusions: PFS at 6 and 9 months predicted OS in this analysis of patients with metastatic UC treated with first-line cisplatin-based chemotherapy and could potentially serve as endpoints in (randomized) phase 2 trials to screen the activity of novel regimens., (Copyright © 2013 American Cancer Society.)

Background: The current study was conducted to develop a pretreatment prognostic model for patients with unresectable and/or metastatic urothelial cancer who were treated with first-line, cisplatin-based chemotherapy., Methods: Individual data were pooled from 399 patients who were enrolled on 8 phase 2 and 3 trials evaluating cisplatin-based, first-line chemotherapy in patients with metastatic urothelial carcinoma. Variables selected for inclusion in the model were combined in a Cox proportional hazards model to produce a points-based nomogram with which to predict the median, 1-year, 2-year, and 5-year survival. The nomogram was validated externally using data from a randomized trial of the combination of methotrexate, vinblastine, doxorubicin plus cisplatin versus docetaxel plus cisplatin., Results: The median survival of the development cohort was 13.8 months (95% confidence interval, 12.1 months-16.0 months); 68.2% of the patients had died at the time of last follow-up. On multivariable analysis, the number of visceral metastatic sites, Eastern Cooperative Oncology Group performance status, and leukocyte count were each found to be associated with overall survival (P < .05), whereas the site of the primary tumor and the presence of lymph node metastases were not. All 5 variables were included in the nomogram. When subjected to internal validation, the nomogram achieved a bootstrap-corrected concordance index of 0.626. When applied to the external validation cohort, the nomogram achieved a concordance index of 0.634. Calibration plots suggested that the nomogram was well calibrated for all predictions., Conclusions: Based on routinely measured pretreatment variables, a nomogram was constructed that predicts survival in patients with unresectable and/or metastatic urothelial cancer who are treated with cisplatin-based chemotherapy. This model may be useful in patient counseling and clinical trial design., (Copyright © 2013 American Cancer Society.)

Introduction: Niemann-Pick disease (NPD) due to acid sphingomyelinase deficiency is a lipid storage disease resulting from the accumulation of sphingomyelin, predominantly within cells of the monocyte-macrophage system. In contrast to other lysosomal storage disorders, skeletal involvement in NPD has not been systematically studied., Methods: Pediatric and adult NPD-B patients underwent medical histories and physical examinations, DEXA scans to measure bone mineral content (BMC), and bone mineral density (BMD) and computed tomography scan or MRI of the abdomen for spleen volume. Z and/or T scores were calculated for the DEXA results. For the pediatric patients adjusted mean BMC (g) and BMD (g/cm(2)) of the lumbar spine, hip, and femoral neck was compared to control subjects. For determination of the relationship between spleen volume and lumbar spine BMD Z score, linear correlation analyses were performed., Results: Lumbar spine Z scores for pediatric patients ranged from 0.061 to -4.879. Statistically significant decreases were observed for the adjusted mean BMC and BMD at the lumbar spine, hip, and femoral neck between the pediatric NPD-B cohort and control subjects. Most NPD-B adults were osteopenic or osteoporotic at one or more sites according the WHO classification of BMD. In NPD-B patients, the degree of splenomegaly was inversely correlated with lumbar spine BMD Z scores., Conclusion: Skeletal involvement is a common and previously unrecognized manifestation of NPD-B. The association between splenomegaly and BMD lends further support to spleen size as an indicator of disease severity.

Purpose: To evaluate the effect of subretinal fluid (SRF), imaged with spectral-domain optical coherence tomography (SD-OCT), on visual acuity outcomes in cases of uveitic macular edema (ME), and to analyze the response of SRF and uveitic ME to therapy., Design: Retrospective case series., Methods: One hundred and one eyes of 75 patients with uveitic ME, as imaged by SD-OCT, were identified at a single tertiary-care referral center. The main outcome measures were best-corrected visual acuity, central subfield thickness (CSFT), and rates of macular edema improvement (≥20% reduction in CSFT), and resolution (defined as reduction of CSFT to <315 μm) of ME at 3 and 6 months follow-up., Results: Forty eyes of 29 patients had SRF on SD-OCT at presentation, which was associated with greater macular thickness (mean CSFT 488 μm vs 362 μm, P = .0001) and worse visual acuity than ME without SRF (20/115 vs 20/51, P = .015). However, eyes with SRF responded more favorably to treatment, and at 3 and 6 months of follow-up they achieved greater rates of improvement and resolution of ME than eyes without SRF (77% improved and 50% resolved at 6 months, vs 20% and 13%, respectively; P = .003 and P = .017, respectively) and recovered to a similar level of visual acuity (20/62 vs 20/42 at 6 months, P = .54)., Conclusions: SRF in uveitic ME is associated with thicker retinas and worse visual acuity on presentation but responds more favorably to treatment and displays greater rates of edema resolution and visual acuity improvement., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Baked egg is tolerated by a majority of egg-allergic children., Objective: To characterize immunologic changes associated with ingestion of baked egg and evaluate the role that baked egg diets play in the development of tolerance to regular egg., Methods: Egg-allergic subjects who tolerated baked egg challenge incorporated baked egg into their diet. Immunologic parameters were measured at follow-up visits. A comparison group strictly avoiding egg was used to evaluate the natural history of the development of tolerance., Results: Of the 79 subjects in the intent-to-treat group followed for a median of 37.8 months, 89% now tolerate baked egg and 53% now tolerate regular egg. Of 23 initially baked egg-reactive subjects, 14 (61%) subsequently tolerated baked egg and 6 (26%) now tolerate regular egg. Within the initially baked egg-reactive group, subjects with persistent reactivity to baked egg had higher median baseline egg white (EW)-specific IgE levels (13.5 kU(A)/L) than those who subsequently tolerated baked egg (4.4 kU(A)/L; P= .04) and regular egg (3.1 kU(A)/L; P= .05). In subjects ingesting baked egg, EW-induced skin prick test wheal diameter and EW-, ovalbumin-, and ovomucoid-specific IgE levels decreased significantly, while ovalbumin- and ovomucoid-specific IgG(4) levels increased significantly. Subjects in the per-protocol group were 14.6 times more likely than subjects in the comparison group (P< .0001) to develop regular egg tolerance, and they developed tolerance earlier (median 50.0 vs 78.7 months; P< .0001)., Conclusion: Initiation of a baked egg diet accelerates the development of regular egg tolerance compared with strict avoidance. Higher serum EW-specific IgE level is associated with persistent baked and regular egg reactivity, while initial baked egg reactivity is not., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Although a creatinine clearance (CrCl) of <60 mL/min, as calculated by the Cockroft-Gault (CG) equation, is a commonly used threshold for "cisplatin-ineligibility," the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has recently emerged as a more accurate method of estimating renal function. We sought to determine the impact of using the CKD-EPI equation for estimating renal function on cisplatin eligibility., Methods: All patients pathologically diagnosed with muscle invasive and/or metastatic bladder urothelial carcinoma (T2-4, N or M positive) at Mount Sinai Medical Center between January 1, 2000, and January 27, 2011, were identified. For each patient, CrCl was estimated by using the CG equation and glomerular filtration rate (GFR) was estimated by using the CKD-EPI equation. The patients were considered cisplatin-ineligible if CrCl <60 mL/min or if GFR was <60 mL/min per 1.73 m(2)., Results: A total of 116 patients were included. The median CrCl estimated by CG was 58.93 mL/min, whereas the median GFR estimated by CKD-EPI was 64.67 mL/min per 1.73 m(2). When using the CG formula, 53% of our cohort was cisplatin ineligible, whereas 46% of the cohort was ineligible when using the CKD-EPI formula. The probability of deeming a patient ineligible when using the CG formula was 17% higher than the probability of deeming a patient ineligible when using the CKD-EPI formula: PR 1.17 (95% CI, 1.03-1.34); P = .0203., Conclusion: In our retrospective study, the CKD-EPI formula was less likely to deem a patient ineligible for cisplatin-based therapy compared with the CG formula. This finding was hypothesis generating, and prospective evaluation is necessary to determine the clinical relevance of using this more accurate method of renal function assessment in chemotherapy decision making., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Advanced glycations end products increase oxidant stress, inflammation, and neurotoxicity. Serum levels are increased in diabetes and aging. We examined the relationship between serum methylglyoxal derivatives (sMG), and cognitive decline, in 267 non-demented elderly., Methods: Tobit mixed regression models assessed the association of baseline sMG with cognitive decline in the Mini Mental State Exam (MMSE) over time, controlling for sociodemographic factors (age, sex, and years of education), cardiovascular risk factors (diabetes and presence of an ApoE4 allele), and kidney function. sMG was assessed by ELISA., Results: The fully adjusted model showed an annual decline of 0.26 MMSE points per unit increase in baseline sMG (p = 0.03). Significance was unchanged as additional risk factors were added to the model. The interactions of sMG with diabetes, sex, age, kidney function, and ApoE4 genotype were not significant., Conclusions: Higher levels of baseline sMG were associated with a faster rate of cognitive decline, after adjusting for several sociodemographic and clinical characteristics. This relationship did not differ by sex, ApoE4 genotype, or diabetes status suggesting its generality. Since subjects were cognitively normal at the beginning of the study, elevated sMG may be indicative of brain cell injury initiated before clinically evident cognitive compromise., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Deep brain stimulation (DBS) at the subthalamic nucleus (STN) is an effective treatment for the motor manifestations of advanced medically refractory Parkinson disease. Because of the medial location of the target, surgical trajectories to the STN may violate the ipsilateral lateral ventricle., Objective: To determine whether violating the ventricle during STN DBS surgery is associated with postoperative confusion., Methods: A retrospective chart review of all STN implantation procedures for Parkinson disease performed by 1 surgeon between January 2005 and September 2008 was performed. Postoperative magnetic resonance imaging was performed in all cases, and each scan was reviewed for evidence of ventricular wall violation. All charts were reviewed for postoperative confusion and/or increased length of hospital stay., Results: A total of 145 leads were implanted in 81 patients over 102 admissions. Forty-three patients underwent contemporaneous bilateral lead implantation; 23 underwent unilateral implantation; and 18 underwent staged bilateral implantation. The cases of 8 patients were complicated by postoperative confusion and increased length of stay. Sixteen magnetic resonance imaging scans demonstrated evidence of ventricular wall violation including all 8 patients with postoperative confusion. The relative risk of having postoperative confusion after traversing the ventricle is 87 (P < .001)., Conclusion: Violating the ventricular system during STN DBS surgery correlated significantly with postoperative altered mental status and subsequent increased length of hospital stay. This finding may explain why cognitive complications are observed more frequently in Parkinson disease patients undergoing DBS at the STN compared with the internal globus pallidus.

Glucocorticoid receptor (GR) agonists increase erythropoiesis in vivo and in vitro. To clarify the effect of the dominant negative GRβ isoform (unable to bind STAT-5) on erythropoiesis, erythroblast (EB) expansion cultures of mononuclear cells from 18 healthy (nondiseased) donors (NDs) and 16 patients with polycythemia vera (PV) were studied. GRβ was expressed in all PV EBs but only in EBs from 1 ND. The A3669G polymorphism, which stabilizes GRβ mRNA, had greater frequency in PV (55%; n = 22; P = .0028) and myelofibrosis (35%; n = 20) patients than in NDs (9%; n = 22) or patients with essential thrombocythemia (6%; n = 15). Dexamethasone stimulation of ND cultures increased the number of immature EBs characterized by low GATA1 and β-globin expression, but PV cultures generated great numbers of immature EBs with low levels of GATA1 and β-globin irrespective of dexamethasone stimulation. In ND EBs, STAT-5 was not phosphorylated after dexamethasone and erythropoietin treatment and did not form transcriptionally active complexes with GRα, whereas in PV EBs, STAT-5 was constitutively phosphorylated, but the formation of GR/STAT-5 complexes was prevented by expression of GRβ. These data indicate that GRβ expression and the presence of A3669G likely contribute to development of erythrocytosis in PV and provide a potential target for identification of novel therapeutic agents.

Object: Chordomas are rare malignant neoplasms arising predominantly at the sacrum and skull base. They are uniformly lethal unless treated with aggressive resection and proton beam irradiation. The authors present results of the surgical management of a large number of patients with clivus chordomas. Factors that influence the surgeon's ability to achieve radical tumor resection are also evaluated., Methods: Between 1991 and 2005, 71 patients with clivus chordomas underwent surgery. The average follow-up was 66 months (median 60 months, range 3-189 months). Sixty-five patients had complete records that were analyzed in the present report. Thirty-five percent of them had undergone surgery before being treated by the authors. They were evaluated with MR imaging and CT scanning and underwent surgery utilizing a variety of skull base techniques aimed at achieving radical excision. Many also underwent postoperative radiation, usually in the form of proton beam therapy. The patients were followed up with serial imaging at regular intervals as well as with neurological evaluation., Results: Radical tumor resection was achieved in 58% of the group. The overall 5-year survival rate was 75%. Radical resection had a positive impact on survival. The ability to achieve radical resection was dependent on the preoperative tumor volume and the number of anatomical areas involved by the tumor. Cranial nerve impairment and CSF leakage were the most frequent postoperative complications., Conclusions: Radical excision is the ideal surgical goal in the treatment of clival chordomas and can be achieved with reasonable risks. Several different surgical approaches may be necessary to accomplish this.

Context: Low concentrations of serum LH and/or oestradiol (E(2)) in girls with early physical signs of precocious puberty pose a diagnostic challenge., Objective: To assess the diagnostic value of the leuprolide stimulation test in female precocious puberty., Design: Retrospective Chart Review., Setting: Outpatient clinic., Patients and Intervention: Thirty-nine girls, 6.9 (1.4) years, with premature stage II-III breast development, with or without pubarche, underwent stimulation testing with subcutaneous leuprolide (20 microg/kg) with the following hormonal measurements in serum: FSH, LH, oestradiol at baseline; FSH and LH at 1 and 2 h; oestradiol at 24 h. Twelve girls with isolated pubarche were also tested with leuprolide., Main Outcome Measure: A pubertal hormonal pattern was defined as at least one of the following: a baseline serum level of LH > or = 0.3 U/l, a baseline oestradiol > or = 37 pmol/l (10 ng/l), a stimulated (peak) LH > or = 5.0 U/l, a stimulated oestradiol > or = 184 pmol/l (50 ng/l) to leuprolide. The hormonal response was related to the clinical course during a period of observation of at least 6 months., Results: Following leuprolide stimulation, the hormonal response was concordant with pubertal progression (n = 23) or lack thereof (n = 16) in all children. At baseline, pubertal serum concentrations of LH and/or oestradiol were associated with pubertal progression in all, while serum prepubertal LH and/or oestradiol concentrations were associated with pubertal progression in approximately 50% of the patients., Conclusions: In girls with early clinical signs of precocious puberty and low serum concentrations of LH and oestradiol in random samples, the LH and oestradiol responses to leuprolide stimulation accurately predict pubertal progression.

Purpose: To study the association between tear osmolarity and dry eye severity grade, based on a modified Dry Eye Workshop (DEWS) scale, and between osmolarity and the signs and symptoms that determine dry eye disease severity., Methods: Nineteen patients with dry eye disease were asked to complete an evaluation of dry eye signs and symptoms composed of the Ocular Surface Disease Index (OSDI) questionnaire, corneal staining with fluorescein, conjunctival staining with lissamine green, tear-film breakup time (TFBUT), Schirmer's test with anesthesia, and tear sample collection. Tear samples were collected in 5-microL microcapillaries. Tear osmolarity was measured in the right eye with a tear osmometer., Results: Tear osmolarity correlated significantly with dry eye severity grade (modified DEWS). Schirmer's test and tear osmolarity correlated significantly at r=-0.52, with Schirmer's test result, with adjustment for age, contributing significantly to the independent estimate of tear osmolarity., Conclusions: Tear osmolarity correlates with dry eye severity and therefore could provide a biomarker for disease severity.

Background: Stress-only imaging saves time and radiation exposure, but apprehension remains about the reliability, diagnostic, and prognostic accuracy of a normal stress-only study. The objective of this study was to determine the prognosis of stress-only SPECT MPI in routine clinical practice., Methods: Patients at lower pre-test risk for CAD presenting for a Tc-99m SPECT MPI over a 2-year period underwent a stress-only protocol. If the stress images were normal (attenuation correction was routinely acquired on all patients), rest imaging was not done. Outcomes of the stress-only group were compared to a full rest-stress protocol cohort. Only patients with normal perfusion and left ventricular function, and no known CAD, were included. All-cause mortality was determined using the Social Security Death Index and specific causes of death were determined using the National Death Index. The difference in all-cause and cardiac mortality between groups in the presence of competing risks was assessed using log-normal survival models., Results: Out of 10,609 patients studied during the time period, 1,673 had a normal stress-only study and 3,237 had a normal rest-stress study. At one year, there were 20 total and 3 cardiac deaths (1.2% and 0.2% mortality) in the stress-only group, and 40 total and 4 cardiac deaths (1.2% and 0.1% mortality) in the rest-stress cohort. At the end of follow-up (40 +/- 9 months), there were 46 total and 7 cardiac deaths (2.7% and 0.4% mortality) in the stress-only group, and 119 total and 17 cardiac deaths (3.7% and 0.5% mortality) in the rest-stress cohort. No significant difference between the stress-only and rest-stress cohorts was found after controlling for confounding variables for both all-cause mortality (p = .94) and cardiac mortality (p = .82)., Conclusions: A normal stress-only MPI has an excellent short-term prognosis (both for all-cause and cardiac mortality) comparable to that of a normal rest-stress MPI study.

Objectives: The objectives were to measure the financial impact of implementing a fully integrated emergency department information system (EDIS) and determine the length of time to "break even" on the initial investment., Methods: A before-and-after study design was performed using a framework of analysis consisting of four 15-month phases: 1) preimplementation, 2) peri-implementation, 3) postimplementation, and 4) sustained effects. Registration and financial data were reviewed. Costs and rates of professional and facility charges and receipts were calculated for the phases in question and compared against monthly averages for covariates such as volume, collections rates, acuity, age, admission rate, and insurance status with an autoregressive time series analysis using a segmented model. The break-even point was calculated by measuring cumulative monthly receipts for the last three study phases in excess of the average monthly receipts from the preimplementation phase, corrected for change in volume, and then plotting this against cumulative overall cost., Results: Time to break even on the initial EDIS investment was less than 8 months. Total revenue enhancement at the end of the 5-year study period was $16,138,953 with an increase of 69.40% in charges and 70.06% in receipts. This corresponds to an increase in receipts per patient from $50 to $90 for professional services and $131 to $183 for facilities charges. Other than volume, there were no significant changes in trends for covariates between the preimplementation and sustained-effects periods., Conclusions: A comprehensive EDIS implementation with process redesign resulted in sustained increases in professional and facility revenues and a rapid initial break-even point. .

Background: Ex vivo generated erythroblasts are being evaluated for transfusion. Expression of balanced levels of globin mRNA is essential for normal red blood cell function and survival but it is unknown whether the expression of the globin genes in ex vivo expanded cells is balanced., Study Design and Methods: Immature erythroblasts (IEs) were expanded in human erythroid massive amplification cultures from blood mononuclear cells of 19 normal donors and four beta(0)-thalassemia patients (for comparison) and induced to mature for 4 days in the presence of erythropoietin. mRNA was prepared from IEs and mature erythroblasts to evaluate the expression of alpha-, beta-, and gamma-globin genes and of adult hemoglobin-stabilizing protein (AHSP) and BCL11A, two proteins directly controlling globin function and/or production. Results were analyzed using Pearson's correlation coefficient, the Wilcoxon signed rank, and the Mann-Whitney rank sum tests., Results: The absolute levels of globin, AHSP, and BCL11A mRNA expressed by erythroblasts generated ex vivo from normal donors were distributed along a 2-log range. With maturation, the levels of gamma-globin and BCL11A mRNA did not decrease while those of alpha-globin, gamma + beta-globins, and AHSP mRNA greatly increased. In normal cells, the modest imbalance (two- to fourfold) observed between alpha- and gamma + beta-globin mRNA was fully compensated by AHSP expression. Thus, the levels of alpha-globin mRNA were correlated with those of gamma + beta-globin (R(2) = 0.93, p < 0.0001) and AHSP (R(2) = 0.86, p < 0.0001)., Conclusions: Ex vivo expanded erythroblasts from normal donors express modestly imbalanced levels of alpha-globin and gamma + beta-globin fully compensated by AHSP expression, likely ensuring normal function and survival.

The complement system has been implicated in the pathogenesis of liver diseases. Human complement component C3 (C3) exists as 2 allotypes, fast (F) and slow (S). We conducted a study to address the influence of these alleles on ischemia-reperfusion (IR) injury and graft survival in liver transplant recipients. Four hundred thirty patients receiving liver transplants from 2000 to 2004 were included. C3 allotypes of 296 donor-recipient pairs were determined and correlated with clinical outcomes. Four groups were analyzed according to the C3 genotype: C3 SS donor and recipient, C3 FS or C3 FF donor and C3 SS recipient, C3 SS donor and C3 FS or C3 FF recipient, and C3 FS or C3 FF donor and recipient. Baseline characteristics of the 4 groups were similar. The mean follow-up time was 4.3 +/- 2.2 years. The 4 groups had similar rates of IR injury (P = 0.16). The hazard ratios for liver allograft survival in the C3 SS donor and recipient group in comparison with the other 3 groups (C3 FS or C3 FF donor and C3 SS recipient, C3 SS donor and C3 FS or C3 FF recipient, and C3 FS or C3 FF donor and recipient) were not significantly different: 1.13 (P = 0.60), 0.99 (P = 0.97), and 1.02 (P = 0.95), respectively. In conclusion, donor and recipient C3 genotypes are not associated with liver transplantation outcomes.

Endothelial like cells (ELCs) are thought to originate from either a hierarchy of endothelial progenitor cells (EPC), monocytes or monocyte derived multipotent progenitor cells (MOMCs). In this report, the ability of CD34(+) cells to generate ELC in vivo was examined using an immunodeficient mouse transplant assay system. The Philadelphia chromosome negative (Ph(-)) myeloproliferative neoplasms (MPN) are associated with the acquired mutation, JAK2V617F. In order to further examine the ability of cord blood and JAK2V617F positive MPN CD34(+) cells to generate ELC, CD34(+) cells were transplanted into NOD/SCID mice. Cells within the livers and lungs of recipient mice had phenotypic and molecular properties of human ELC as examined using RT-PCR, flow cytometric analysis and fluorescence microscopy. These cells possessed either human wild type JAK2 or JAK2V617F indicating that they were derived from the transplanted human cells and that a fraction of such cells were involved by the malignant process. Furthermore, human CD144(+) cells isolated from the livers of recipient mice formed clusters in vitro composed of ELC, which contained either wild type JAK2 or JAK2V617F suggesting that these cells are derived from either MOMC or EPC that have an extensive proliferative capacity as well as some degree of self renewal capacity. These studies indicate that adult CD34(+) cells can be affected by JAK2V617F and that they can generate ELC which might play a role in the development of thrombosis in patients with MPN.

Objective: Prior studies have shown an association between fast-food restaurants and adolescent body size. Less is known about the influence of neighborhood food stores on a child's body size. We hypothesized that in the inner-city, minority community of East Harlem, New York, the presence of convenience stores and fast-food restaurants near a child's home is associated with increased risk for childhood obesity as measured by body mass index (BMI)., Design: Baseline data of 6- to 8-year-old East Harlem boys and girls (N=323) were used. Anthropometry (height and weight) was conducted with a standardized protocol. Food-store data were collected via a walking survey. Stores located within the same census block as the child's home address were identified by using ArcGIS 8.3. We computed age- and sex-specific BMI percentiles by using national norms of the Centers for Disease Control and Prevention. Using odds ratios, we estimated risk of a child's BMI percentile being in the top tertile based on number and types of food stores on their census blocks., Results: Convenience stores were present in 55% of the surveyed blocks in which a study particpant lived and fast-food restaurants were present in 41%. Children (n=177) living on a block with 1 or more convenience stores (range, 1-6) were more likely to have a BMI percentile in the top tertile (odds ratio 1.90, 95% confidence interval, 1.15-3.15) compared with children having no convenience stores (n=146)., Conclusions: The presence of convenience stores near a child's residence was associated with a higher BMI percentile. This has potential implications for both child- and neighborhood-level childhood obesity interventions.

The objective of this study is to assess dyskinesias in 34 Parkinson's disease patients randomized to receive bilateral fetal nigral transplantation with 4 donors per side (12), 1 donor per side (11), or placebo (11). Videotape recordings were performed at the baseline, 3, 6, 12, 18, and 24 month visits during the "practically defined off" (12 hours after last evening dopaminergic therapy) and "best on" (best response following morning dopaminergic therapy) states. Videotapes were analyzed in random order by a blinded investigator. Dyskinesias during "best on" (on-medication dyskinesia) were observed in all, but 1 patient at baseline, and in all patients at each subsequent visit. There were no differences between groups. No patient had dyskinesia at baseline in "practically-defined off" ("off-medication" dyskinesia). Following transplantation, off-medication dyskinesia was observed in 13 of 23 patients, but not in any patient in the placebo group (P = 0.019). There was no difference in dyskinesia score between patients in the 1 and 4 donor groups. On-medication dyskinesias were typically generalized and choreiform, whereas off-medication dyskinesias were usually repetitive, stereotypic movements in the lower extremities with residual Parkinsonism in other body regions. Off-medication dyskinesias are common following transplantation and may represent a prolonged form of diphasic dyskinesias., ((c) 2008 Movement Disorder Society.)

Background: Gender related differences in respiratory disease have been documented. The aim of this study was to investigate gender related differences in respiratory findings by occupation. We analyzed data from 12 of our previously published studies., Methods: Three thousand and eleven (3011) workers employed in "organic dust" industries (1379 female and 1632 male) were studied. A control group of 806 workers not exposed to any kind of dust were also investigated (male = 419, female = 387). Acute and chronic respiratory symptoms and lung function were measured. The weighted average method and the Mantel-Haentszel method were used to calculate the odds ratios of symptoms. Hedge's unbiased estimations were used to measure lung function differences between men and women., Results: There were high prevalences of acute and chronic respiratory symptoms in all the "dusty" studied groups compared to controls. Significantly less chronic cough, chronic phlegm as well as chronic bronchitis were found among women than among men after the adjustments for smoking, age and duration of employment. Upper respiratory tract symptoms by contrast were more frequent in women than in men in these groups. Significant gender related lung function differences occurred in the textile industry but not in the food processing industry or among farmers., Conclusion: The results of this study suggest that in industries processing organic compounds there are gender differences in respiratory symptoms and lung function in exposed workers. Whether these findings represent true physiologic gender differences, gender specific workplace exposures or other undefined gender variables not defined in this study cannot be determined. These data do not suggest that special limitations for women are warranted for respiratory health reasons in these industries, but the issue of upper respiratory irritation and disease warrants further study.

Breast cancer in African-American (AA) women occurs at an earlier age than in European-American (EA) women and is more likely to have aggressive features associated with poorer prognosis, such as high-grade and negative estrogen receptor (ER) status. The mechanisms underlying these differences are unknown. To address this, we conducted a case-control study to evaluate risk factors for high-grade ER- disease in both AA and EA women. With the onset of the Health Insurance Portability and Accountability Act of 1996, creative measures were needed to adapt case ascertainment and contact procedures to this new environment of patient privacy. In this paper, we report on our approach to establishing a multicenter study of breast cancer in New York and New Jersey, provide preliminary distributions of demographic and pathologic characteristics among case and control participants by race, and contrast participation rates by approaches to case ascertainment, with discussion of strengths and weaknesses.

Background: Polychlorinated biphenyls and other organochlorines have contaminated the Hudson River and New York/New Jersey Harbor for many decades. Although body burdens and health effects resulting from exposure to these pollutants have been measured in other populations, little is known about anglers from the lower Hudson area., Methods: Anglers were recruited from fishing clubs and along piers on the lower Hudson River. One hundred twenty-five participants provided blood samples and questionnaire information. Serum was analyzed at Mount Sinai School of Medicine for organochlorines., Results: Mean concentration of total PCB congeners was 4.78 microg/L. A non-significant adjusted mean difference of -0.59 microg/L was observed between local fish eaters and non-eaters with higher levels among the non-eaters. Similar negative, but non-significant associations were observed for p,p'-DDT, HCB, and beta-BHC. For pp'-DDE, and several chlordane residues, levels were higher among anglers reporting local fish consumption, but the difference was statistically significant only for TN., Conclusions: These findings suggest eating fish from the lower Hudson River and NY/NJ harbor is not associated with an increased body burden of PCBs or most other organochlorines.

Background: Evidence is mounting that environmental exposures contribute to causation of disease in children. Yet few pediatricians are trained to diagnose, treat, or prevent disease of environmental origin., Objectives: To develop a cadre of future leaders in pediatric environmental health (PEH), the Ambulatory Pediatric Association (APA) launched a new 3-year fellowship in 2001-the world's first formal training program in PEH. Sites were established at Boston Children's Hospital, Mount Sinai School of Medicine, George Washington University, University of Cincinnati, and University of Washington. Fellows are trained in epidemiology, biostatistics, toxicology, risk assessment, and preventive medicine. They gain clinical experience in environmental pediatrics and mentored training in clinical research, policy development, and evidence-based advocacy. Thirteen fellows have graduated. Two sites have secured follow-on federal funding to enable them to continue PEH training., Discussion: To assess objectively the program's success in preparing fellows for leadership careers in PEH, we conducted a mailed survey in 2006 with follow-up in 2007., Conclusions: Fifteen (88%) of 17 fellows and graduates participated; program directors provided information on the remaining two. Nine graduates are pursuing full-time academic careers, and two have leadership positions in governmental and environmental organizations. Ten have published one or more first-authored papers. Seven graduates are principal investigators on federal or foundation grants. The strongest predictors of academic success are remaining affiliated with the fellowship training site and devoting < 20% of fellowship time to clinical practice., Conclusion: The APA fellowship program is proving successful in preparing pediatricians for leadership careers in PEH.

Background: Exposure to dust in the cotton industry is associated with respiratory dysfunction. Healthy subjects challenged with cotton bract extract (CBE) develop transient airway hyperresponsiveness. CBE, a major component of cotton dust, is potentially an important agent for studying byssinosis., Objectives: To compare airway responses to cotton dust extract (CDE) and CBE in healthy subjects., Methods: In 21 healthy, non-smoking subjects we compared the effects of CBE and CDE in a double-blind random order, following a 10-min aerosol inhalation. The response to methacholine (MCh) 2 h following CBE or CDE was measured. Lung function was recorded using maximal (MEFV) and partial expiratory flow volume (PEFV) curves, measuring MEF at 60% of baseline vital capacity below total lung capacity [MEF40%(P)] on the PEFV curve. Responders were subjects who developed a 20% or greater fall in MEF40%(P) following extract challenge. Endotoxin levels were low for CBE (5.71 EU/mg) and CDE (31.88 EU/mg)., Results: There were 18 responders to CBE and 17 responders to CDE. The average maximal falls in MEF40%(P) were 70 +/- 4.9 and 70 +/- 4.4% of baseline (nonsignificant) following CBE and CDE, respectively. All subjects enhanced their MCh response following CBE or CDE. The MCh dose which reduced MEF40%(P) by 40% was identical for CBE and CDE (1.3 microg/ml)., Conclusions: We conclude that CBE and CDE exert similar physiologic effects., (Copyright 2006 S. Karger AG, Basel.)

Upregulation of N-cadherin in epithelial tumor cells has been shown to contribute to the invasive/metastatic phenotype. It remains however to be determined whether N-cadherin is increased in human breast cancers with enhanced malignant potential. We examined a large number of invasive breast cancer specimens (n = 114) for N- and E-cadherin. These specimens compared invasive duct carcinomas (IDCs) of varying histologic grades with an aggressive subtype, invasive micropapillary carcinoma of the breast (MPAP), which has a high propensity for lymphatic invasion and lymph node metastasis. Staining scores for N- and E-cadherin were compared between non-MPAP and MPAP IDCs, and between the invasive and ductal carcinoma in situ (DCIS) of each IDC using statistical analysis. We found that N-cadherin was expressed in 76% of MPAP and 52% of non-MPAP carcinomas, and E-cadherin in 57% of MPAP and 36% of non-MPAP tumors. More MPAP (25%) compared to non-MPAP (5%) tumors expressed both cadherins. Of the two cadherins, N-cadherin was significantly associated with MPAP tumors (p = 0.033) compared to E-cad (p = 0.171). Moreover, in the majority of tumors that were positive for N-cadherin, the staining scores were increased in the IDC relative to intraductal components, and this effect was more dramatic in the MPAP carcinomas. This difference for N-cadherin was greater than the corresponding difference for E-cadherin in the MPAP group (p = 0.005), whereas such changes were not significant in the non-MPAP group (p = 0.10). Thus, N-cadherin is associated with tumor aggressiveness and metastatic potential and may contribute to tumor progression.

Purpose: Early age at menarche increases future disease risk. Secular decline in age at menarche has been attributed to body size characteristics, diet, and energy expenditure. Risk factors for puberty have been less frequently explored., Methods: A cross-sectional study of 186 New York Metropolitan Area, 9-year-old girls (54 African-American, 70 Hispanic, 62 Caucasians) used interviewer-administered questionnaires to assess exposures. Height and weight were measured. Pediatricians assessed pubertal development according to Tanner stages., Results: African-Americans were more likely than Caucasians to have achieved puberty as determined by breast or hair development (stage 2 or higher) [age-adjusted odds ratios and 95% confidence intervals = 4.91 (2.15-11.19) and 4.25 (1.85-9.77), respectively]. Pubertal development was similar among Hispanics and Caucasians. Adiposity and height were significantly positively associated with breast or hair development. More sedentary activity hours non-significantly increased the likelihood of hair development. Lower energy, but higher polyunsaturated fat, consumption were suggestive of an association with breast development. Vitamin C and hair development were inversely related. No other nutrients or physical activity measures were related to pubertal development., Conclusions: Results are consistent with height and adiposity being associated with pubertal development. Sedentary activity or diet might possibly influence maturation.

Pesticides, applied in large quantities in urban communities to control cockroaches, pose potential threats to health, especially to children, who have proportionately greater exposures and unique, developmentally determined vulnerabilities. Integrated pest management (IPM) relies on nonchemical tools--cleaning of food residues, removal of potential nutrients, and sealing cracks and crevices. Least toxic pesticides are used sparingly. To evaluate IPM's effectiveness, the Mount Sinai Children's Environmental Health and Disease Prevention Research Center, in partnership with two community health centers in East Harlem, New York City (NY, USA), undertook a prospective intervention trial. Families (n = 131) enrolled when mothers came to the centers for prenatal care. Household cockroach infestation was measured by glue traps at baseline and 6 months afterward. The intervention group received individually tailored IPM education, repairs, least-toxic pest control application, and supplies, with biweekly pest monitoring for 2 months and monthly for 4 months. The control group, residing in East Harlem and demographically and socioeconomically similar to the intervention group, received an injury prevention intervention. The proportion of intervention households with cockroaches declined significantly after 6 months (from 80.5 to 39.0%). Control group levels were essentially unchanged (from 78.1 to 81.3%). The cost, including repairs, of individually tailored IPM was equal to or lower than traditional chemically based pest control. These findings demonstrate that individually tailored IPM can be successful and cost-effective in an urban community.

Sudden-onset sleep episodes while driving have been reported in Parkinson's disease (PD) patients, and termed sleep attacks because they were reported to be irresistible and to occur without warning. We postulate that these episodes are due to excessive daytime sleepiness secondary to the high frequency of sleep disorders in PD patients and the sedative effects of dopaminergic medications. We assessed the frequency and relationship between excess daytime sleepiness and sleep episodes while driving (SE) in patients with PD. We evaluated 101 consecutive PD patients presenting to the Movement Disorder Center at the Mount Sinai School of Medicine using a questionnaire that incorporated a subjective estimate of sleepiness, the Epworth Sleepiness Scale (ESS) and information on disease severity and dopaminergic medications. One hundred age-matched respondents without PD served as a control population. Excess daytime sleepiness was reported in 76% of PD patients compared to 47% of controls (P < 0.05). The mean ESS scores for PD patients was 9.1 +/- 6.1 versus 5.7 +/- 4.4 in controls (P < 0.001). ESS scores > or =10 were observed in 40.6% of PD patients compared to 19% of controls (P < 0.01) and 24% of PD patients had scores > or =15, compared to 5% of controls (P < 0.001). Sleep episodes while driving were experienced by 20.8% of PD drivers compared to 6% of control drivers (P < 0.05). The mean daily levodopa (L-dopa) dose equivalent was 1,142 +/- 858 mg in PD drivers who experienced a SE while driving compared to 626 +/- 667 mg in those who had not (P < 0.05). Similarly, ESS was significantly greater in drivers with a SE than in those without (11.6 +/- 6.4 vs. 8.4 +/- 4.1; P < 0.05). Logistic regression analysis demonstrated that ESS and mean daily L-dopa dose equivalents were predictors of sleep episodes while driving, whereas age, gender, disease severity, and individual dopaminergic agents were not. These findings support the notion that sleep episodes while driving in PD patients are related to excess daytime sleepiness and dopaminergic load. Physicians should advise and treat patients accordingly., (Copyright 2003 Movement Disorder Society)

Evidence is growing that indoor pesticide exposure is of considerable magnitude in the United States and that pesticide concentrations may be especially high in urban areas. Of particular concern is exposure of pregnant women because animal data suggest that exposure to pesticides during pregnancy and early life may impair neurodevelopment in the offspring. To investigate the relationship between prenatal exposure to indoor pesticides and infant growth and development, we are conducting a prospective, multiethnic cohort study of mothers and infants delivered at Mount Sinai Hospital in New York City. This article provides data on pesticide exposure based on questionnaire items and analysis of maternal urinary metabolite levels among 386 women. Both the questionnaire and laboratory data revealed that exposure to indoor pesticides was considerable. The proportion of women estimated from questionnaire data as having been exposed during pregnancy to indoor pesticides (approximately 70%) was somewhat lower than the 80-90% of American households who reportedly used pesticides in previous surveys, but some of the latter surveys included both indoor and outdoor pesticide use. Urinary metabolite levels of 3,5,6-trichloro-2-pyridinol (TCPy; median = 11.3 micro g/g creatinine), phenoxybenzoic acid (PBA; median =19.3 micro g/g creatinine), and pentachlorophenol (PCP; median =7.3 micro g/g creatinine) were higher than those reported in other studies of adults in the United States. Furthermore, no associations were evident between the pesticide questionnaire data and the urinary metabolites. Assessments of sociodemographic and building characteristics with questionnaire data and the metabolite levels revealed no consistent trends. Significant temporal variations were observed for urinary PBA but not TCPy or PCP. The temporal variations for PBA were consistent with seasonal spraying of pyrethroid pesticides. These data underscore the need to assess the potentially adverse effects of pesticide exposure on fetuses and infants and the importance of finding alternative methods for pest management to reduce pesticide exposures.

The ideal technology for screening single-nucleotide polymorphisms requires high throughput with minimal cost per sample, minimal usage of valuable DNA resources, and maximal flexibility for assessment of new polymorphisms. We demonstrate here the feasibility of kinetic allele-specific PCR with DNA pooling (S. Germer et al., Genome Res., 10: 258-266, 2000) in a population study that satisfies all of the mentioned criteria and offers a powerful new tool for detecting meaningful polymorphic differences in candidate gene association studies and genome-wide linkage dysequilibrium scans. Three individuals prepared pooled DNA samples from 269 individuals separated into three racial/ethnic groups: Caucasians (n = 56), African-Americans (n = 86), and Hispanics (n = 127). We used kinetic allele-specific PCR to determine the allele frequencies of the common paraoxonase 1 polymorphism, PON1 Q191R, in these pools. Paraoxonase 1 is a critical enzyme for inactivating neurotoxic intermediates in the metabolism of organophosphates. In a blinded test of the technology, these nine pooled DNA samples were sent to Roche for genotyping by kinetic allele-specific PCR. The allele frequencies found were 0.266 +/- 0.011, 0.386 +/- 0.011, and 0.617 +/- 0.010, respectively, which were comparable to the frequencies of 0.269, 0.403, and 0.622 determined by PCR-restriction fragment length polymorphism analysis. These same samples were genotyped on two kinetic PCR platforms from different manufacturers, using three different DNA polymerases. The results were comparable between both platforms and among all three polymerases. The results demonstrate a powerful new technology for determining frequencies of single-nucleotide polymorphisms in an epidemiological study.

In vivo x-ray fluorescence bone lead measurements assess long-term lead exposure. Tibia, calcaneus, and patella are the most commonly sampled bones. Patella measurements also include lead signals from the distal femur, proximal tibia, and synovium. It is therefore important to know whether the orientation of the patella relative to the measurement system substantially affects the measured patella lead concentrations and their measurement uncertainties. This study examined whether these parameters exhibited a dependence on the orientation of the patella with respect to the measurement system, a dependence that could arise from varying nonpatella contributions. There was no effect of orientation on measured patella lead concentration, but there was a highly significant effect of orientation on the measurement uncertainty. These data do not conclusively show that there are no nonpatella contributions to a patella lead measurement; rather, that any such contributions are not a function of measurement orientation over the range of orientations considered. Further study is required if the contribution of nonpatella tissues to a patella lead XRF-measured concentration is to be fully addressed. This study also filled a gap in the literature by quantifying the within-patella (29%) and between-patella (71%) variability of measured patella lead concentrations from replicate measures of nine patellae.

A pilot study was conducted in Morelos, Mexico in March 1999 to assess the body burden of lead in 24 Mexican women of childbearing age. Lead levels were measured in whole blood and at three bone sites: two primarily trabecular (calcaneus and patella) and one primarily cortical (tibia). Demographic and reproductive characteristics of the women and potential sources of lead exposure were gathered by a direct interview. An inverse relationship was noted between months of lactation and age-adjusted calcaneus lead level (P = 0.001). No association was observed between age-adjusted patella or tibia lead level and months of lactation (P = 0.15). Blood lead levels were positively associated with the use of lead-glazed ceramics (P = 0.01). Bone and blood lead levels were observed to be 77% higher in these rural Mexican women than in urban New York City women. This pilot study provides further limited evidence for the hypothesis that lead mobilization occurs during lactation.

Background: Studies of aortic arch plaques with transesophageal echocardiography have demonstrated that complex aortic arch plaques (CAPs) greater than or equal to 4 mm in thickness are associated with ischemic stroke. Recent studies have demonstrated that the morphological features of plaques may aid in the identification of aortic plaques that are more likely to be associated with embolic stroke., Objective: To identify aortic plaques that are more likely to be associated with embolic stroke by means of their morphological features., Methods: Transcutaneous B-mode ultrasonography was used to image aortic arch plaques in 500 consecutive patients. The criteria used to identify the morphological features of carotid artery plaques that are more likely to be associated with ischemic stroke (heterogeneous rather than homogeneous) were applied to aortic arch plaques. Statistical comparisons were made using the Fisher exact test., Results: Ischemic symptoms (eg, stroke, transient ischemic attack, and amaurosis fugax) were present in 38% of 104 patients with CAP and in 34% of 391 patients without CAP. Nineteen (51%) of 37 patients with heterogeneous CAP were symptomatic. Twenty-one (31%) of 67 patients with homogeneous CAP were symptomatic (P = .04)., Conclusion: Transcutaneous B-mode ultrasonography of the aortic arch can help to identify heterogeneous plaques that are more likely to be associated with ischemic stroke using morphological criteria derived from studies of carotid artery plaque.

Objective: To determine the prognostic significance and pathophysiologic implication of intraventricular extension of supratentorial intracerebral hemorrhage., Design: Prospective study., Setting: Acute stroke and neurointensive care units of a tertiary care hospital., Patients: One hundred twenty-nine patients with supratentorial intracerebral hemorrhage, managed medically., Interventions: Two patients had intraventricular catheters placed for external drainage. No patient received thrombolytics or surgical evacuation of clot., Measurements and Main Results: Of the 129 patients, 47 had intraventricular extension of their hemorrhages. These patients had larger intraparenchymal hemorrhages (36.6 cm3 vs. 15.0 cm3) and lower initial Glasgow Coma Scale scores (mean, 9.6 vs. 13.7). Their 30-day mortality rate was 43% compared with only 9% among those without ventricular extension. Univariate and multivariate logistic regression modeling was used to assess the prognostic significance of various measures of intraventricular hemorrhage. The presence of intraventricular hemorrhage, the number of ventricles containing blood, fourth ventricular blood, and intraventricular hemorrhage volume were each related to 30-day mortality in a univariate analysis, but only intraventricular hemorrhage volume contributed significantly to outcome prediction in the presence of Glasgow Coma Scale score., Conclusions: Volume of intraventricular hemorrhage is an important determinant of outcome in supratentorial intracerebral hemorrhage.

Objective: To determine the effects of immunodeficiency, nutritional status, and concurrent systemic disease on peripheral nerve function in acquired immunodeficiency syndrome., Design: Survey of subjects infected with human immunodeficiency virus (HIV), recruited as part of a prospective study of neuromuscular complications of HIV infection., Setting: A neuro-acquired immunodeficiency syndrome outpatient clinic in a university medical center., Patients: A consecutive sample of 251 HIV-infected individuals. Primary care providers referred subjects to the study for evaluation of neurologic symptoms or for prospective neurologic assessment., Main Outcome Measures: Standardized history and neurologic examination, laboratory tests (complete blood cell count, serum albumin level, vitamin B12 level, and T-lymphocyte subsets), and electrophysiologic testing of sural, tibial, and ulnar nerves., Results: The most frequent neurologic diagnosis was distal symmetrical polyneuropathy (DSP) (38%). The most common clinical features were nonpainful paresthesias (71%), abnormalities of pain and temperature perception (71%), and reduced or absent ankle reflexes (66%). Patients with DSP were significantly older (P=.009), and had lower CD4 lymphocyte cell counts (P=.004) and lower hemoglobin levels (P=.004) than those without DSP. Deterioration of values on nerve conduction studies, irrespective of the clinical diagnosis of DSP, was significantly correlated with low CD4 counts, aging, abnormal serum albumin and hemoglobin levels, and weight loss. Most of these factors co-correlated, and, with the exception of age, no single variable significantly accounted for changes in results of nerve conduction studies when the influence of other factors was eliminated., Conclusion: The combination of several factors, including age, immunosuppression, nutritional status, and chronic disease, contributes to distal peripheral nerve dysfunction in HIV infection.

This study was designed to measure recurrent stroke rates and identify their determinants in a mixed ethnic population. A cohort of 299 patients (110 black, 57 Hispanic and 132 white) admitted to a large urban hospital with an acute stroke between November 1, 1991, and July 1, 1993, was followed for a mean of 17.8 months. Demographic and historical data and stroke subtype and severity were recorded at the time of the index stroke. The main outcome measure was stroke recurrence. The unadjusted relative risk of stroke recurrence for blacks, relative to white, was 2.0 (95% CI: 0.9-4.4) and for Hispanics, relative to whites, it was 2.6 (95% CI: 1.08-60). Ethnicity appeared to be associated with recurrence risk only among first-ever strokes: the risk for blacks, relative to whites, was 2.4 (95% CI: 1.02-5.5) and for Hispanics it was 2.9 (95% CI: 1.2-7.4). None of the other putative risk factors for stroke recurrence identified at the time of initial hospitalization were associated with risk of recurrence.

African-Americans and probably Latinos are at increased risk of stroke compared with white, non-Latino Americans. This study seeks to determine if the known risk factors for stroke can account for this increased risk. In this case-control study controls (neighborhood volunteers) were group-matched to acute stroke cases by ethnicity in a ratio of approximately 2:1 for African-Americans and Latinos and 1:1 for whites. Extensive historical, clinical and laboratory data were collected on each subject. For each ethnic group cases were somewhat older and less well-educated than the volunteer controls. Patients in each ethnic group were similar with regard to time from stroke onset to hospital admission, stroke severity, length of stay, discharge disposition and mortality rate. With minor exceptions the distributions of stroke subtypes within each ethnic group appeared similar to those previously reported. Subject recruitment for this case-control study was completed in the manner and time frame planned. Analysis of risk factor information from this sample should provide valuable information regarding the relative risk associated with the major modifiable risk factors for stroke in the minority groups studied.

Asbestos fibers are widespread environmental carcinogens whose mutagenicity is now established. Nonetheless, the molecular nature of these mutations and the mechanisms by which they accelerate carcinogenesis remain poorly understood. We have assessed the ability of asbestos fibers to promote homologous recombination, a potent mechanism for generating intrachromosomal rearrangements, such as deletions, and mitotic recombination. For this, we have developed a new assay which determines the extent to which a marker gene present in DNA introduced by asbestos can recombine with homologous genes residing in a transfected cell. We have demonstrated that Calidria chrysotile fibers are mutagenic and are able to mediate transfection of molecularly marked mutant lacI genes in a manner that results in their preferential recombination with homologous wild-type genes in the transfected cell. Asbestos induced recombination events may play a significant role in asbestos mutagenesis and carcinogenesis, and promotion of recombination may underlie the well-recognized synergy of asbestos with other carcinogens.

Objectives: To analyse quantitatively the relations of spirometric lung function (forced vital capacity (FVC)) to radiographic interstitial pulmonary fibrosis (assessed by the International Labour Organisation (ILO) profusion score of small irregular opacities) in two large workforces exposed to different intensities of asbestos. These analyses consider the question whether a similar profusion score n differently exposed workers is associated with a similar effect on lung function., Methods: Surveys of two workforces, insulators (n = 2611) and sheet metal workers (n = 1245), by the same investigators allowed comparison of the effects of the two levels of exposure to asbestos. The two groups were of similar age and had similar percentages of non-smokers and smokers. All radiographs were read by the same expert reader., Results: Consistent with their less continuous and less intense exposure to asbestos, metal workers had: (a) far less frequent radiographic asbestosis (profusion score > or = 1/0, 17.5% v 59.6% for insulators): (b) less severe radiographic asbestosis (only 1.1% had scores > or = 2/1 v 13.3% of insulators); (c) a similar slope to that seen in insulators for the relation between FVC and profusion score when pleural thickening was absent; (d) less frequent pleural fibrosis (36% v 75%); and (e) less frequent restrictive impairment (23% v 33%). In both insulators and metal workers, lung function was below normal even when lung fields were normal, FVG fell with increasing profusion, it was lower in smokers and in those with pleural thickening at comparable profusion scores, and these was no difference in FVC between scores 0/1 and 1/0., Conclusion: The decrease in FVC with increasing profusion score in both workforces as well as the similar slopes for the relation between FVG and profusion score and the similar FVG at similar scores in the absence of pleural thickening confirm the ILO profusion score as an acceptable assessment of pulmonary fibrosis.