Showing papers by "Jewish Hospital published in 2012"

Expression of ck-19, galectin-3 and hbme-1 in the differentiation of thyroid lesions: systematic review and diagnostic meta-analysis

Abstract: To distinguish between malignant and benign lesions of the thyroid gland histological demonstration is often required since the fine-needle aspiration biopsy method applied pre-operatively has some limitations. In an attempt to improve diagnostic accuracy, markers using immunocytochemistry and immunohistochemistry techniques have been studied, mainly cytokeratin-19 (CK-19), galectin-3 (Gal-3) and Hector Battifora mesothelial-1 (HBME-1). However, current results remain controversial. The aim of the present article was to establish the diagnostic accuracy of CK-19, Gal-3 and HBME-1 markers, as well as their associations, in the differentiation of malignant and benign thyroid lesions. A systematic review of published articles on MEDLINE and The Cochrane Library was performed. After establishing inclusion and exclusion criteria, 66 articles were selected. The technique of meta-analysis of diagnostic accuracy was employed and global values of sensitivity, specificity, area under the summary ROC curve, and diagnostic odds ratio (dOR) were calculated. For the immunohistochemistry technique, the positivity of CK-19 for the diagnosis of malignant thyroid lesions demonstrated global sensitivity of 81% and specificity of 73%; for Gal-3, sensitivity of 82% and specificity of 81%; and for HBME-1, sensitivity of 77% and specificity of 83%. The association of the three markers determined sensitivity of 85%, specificity of 97%, and diagnostic odds ratio of 95.1. Similar results were also found for the immunocytochemistry assay. This meta-analysis demonstrated that the three immunomarkers studied are accurate in pre- and postoperative diagnosis of benign and malignant thyroid lesions. Nevertheless, the search for other molecular markers must continue in order to enhance this diagnostic accuracy since the results found still show a persistency of false-negative and false-positive tests. Http://www.diagnosticpathology.diagnomx.eu/vs/3436263067345159

Unilateral Radiotherapy for the Treatment of Tonsil Cancer

Abstract: Purpose To assess, through a retrospective review, clinical outcomes of patients with squamous cell carcinoma of the tonsil treated at the M. D. Anderson Cancer Center with unilateral radiotherapy techniques that irradiate the involved tonsil region and ipsilateral neck only. Methods and Materials Of 901 patients with newly diagnosed squamous cell carcinoma of the tonsil treated with radiotherapy at our institution, we identified 102 that were treated using unilateral radiotherapy techniques. All patients had their primary site of disease restricted to the tonsillar fossa or anterior pillar, with n = 17 patients), T1 ( n = 52), or T2 ( n = 33) disease, with Nx ( n = 3), N0 ( n = 33), N1 ( n = 23), N2a ( n = 21), or N2b ( n = 22) neck disease. Results Sixty-one patients (60%) underwent diagnostic tonsillectomy before radiotherapy. Twenty-seven patients (26%) underwent excision of a cervical lymph node or neck dissection before radiotherapy. Median follow-up for surviving patients was 38 months. Locoregional control at the primary site and ipsilateral neck was 100%. Two patients experienced contralateral nodal recurrence (2%). The 5-year overall survival and disease-free survival rates were 95% and 96%, respectively. The 5-year freedom from contralateral nodal recurrence rate was 96%. Nine patients required feeding tubes during therapy. Of the 2 patients with contralateral recurrence, 1 experienced an isolated neck recurrence and was salvaged with contralateral neck dissection only and remains alive and free of disease. The other patient presented with a contralateral base of tongue tumor and involved cervical lymph node, which may have represented a second primary tumor, and died of disease. Conclusions Unilateral radiotherapy for patients with TX–T2, N0–N2b primary tonsil carcinoma results in high rates of disease control, with low rates of contralateral nodal failure and a low incidence of acute toxicity requiring gastrostomy.

Childhood risk factors predict cardiovascular disease, impaired fasting glucose plus type 2 diabetes mellitus, and high blood pressure 26 years later at a mean age of 38 years: the Princeton-lipid research clinics follow-up study

Abstract: The objective was to assess whether pediatric risk factors predict cardiovascular disease (CVD), impaired fasting glucose (IFG) + type 2 diabetes mellitus (T2DM), and high blood pressure (HBP) in young adulthood. We performed a prospective follow-up of 909 public-parochial suburban schoolchildren first studied at ages 6 to 18 years and 26 years later at a mean age of 38 years. Pediatric triglycerides (TGs), blood pressure, low-density lipoprotein cholesterol, body mass index, and glucose above and high-density lipoprotein cholesterol below established pediatric cutoffs, along with race, cigarette smoking, family history of CVD, T2DM, and HBP, were assessed as determinants of young adult CVD, a composite variable including IFG + T2DM and HBP. By stepwise logistic regression, adult CVD (19 yes, 862 no) was associated with pediatric high TG (odds ratio [OR], 5.85; 95% confidence interval [CI], 2.3-14.7). High TG in pediatric probands with young adult CVD was familial and was associated with early CVD in their high-TG parents. Adult IFG + T2DM (114 yes, 535 no) was associated with parental T2DM (OR, 2.2; 95% CI, 1.38-3.6), high childhood glucose (OR, 4.43; 95% CI, 2-9.7), and childhood cigarette smoking (OR, 1.64; 95% CI, 1.03-2.61). Adult HBP (133 yes, 475 no) was associated with pediatric high body mass index (OR, 2.7; 95% CI, 1.7-4.3) and HBP (OR, 2.5; 95% CI, 1.5-4.3). Pediatric risk factors are significantly, independently related to young adult CVD, IFG + T2DM, and HBP. Identification of pediatric risk factors for CVD, IFG + T2DM, and HBP facilitates initiation of primary prevention programs to reduce development of adult CVD, IFG + T2DM, and HBP.

Modern age pathology of pulmonary arterial hypertension

Abstract: Introduction: The impact of modern treatments of pulmonary arterial hypertension (PAH) on pulmonary vascular pathology remains unknown. The last series reporting the pathology of severe pulmonary hypertension date back two decades, well before usage of current therapies for the disease. Methods: Assessment of pulmonary vascular remodelling and inflammation in 62 PAH and 28 control explanted lungs systematically sampled, with matched clinical data. The tissue was obtained by the Pulmonary Hypertension Breakthrough Initiative. Results: Total wall, intima, and media fractional thicknesses of pulmonary arteries were increased in the PAH group versus the controls, and correlated with pulmonary hemodynamics. Despite a high variability of morphological measurements within a given PAH lung and among all PAH lungs, pathological subphenotypes were detected in cohorts of PAH lungs. This included a subset of lungs lacking intima or media remodeling, which had similar numbers of profiles of plexiform lesions as those in lungs with more pronounced remodeling. Perivascular inflammation was present in a high number of PAH lungs and correlated with mean pulmonary arterial pressure (mPAP) as well as intima and total wall thickness. The number of profiles of plexiform lesions was significantly lower in lungs of patients who were never treated with prostacyclin or its analogues. Conclusions: Our results indicate that multiple features of pulmonary vascular remodeling are present in patients treated with modern PAH regimens. Perivascular inflammation may have an important role in the processes of vascular remodeling, all of which may ultimately lead to increased pulmonary artery pressure.

Risk factors for cardiovascular disease and type 2 diabetes retained from childhood to adulthood predict adult outcomes: the Princeton LRC Follow-up Study

Abstract: Pediatric risk factors predict adult cardiovascular disease (CVD) and type 2 diabetes (T2DM), but whether they predict events independently of adult risk factors is not fully known. Assess whether risk factors for CVD and T2DM retained from childhood to adulthood predict CVD and T2DM in young adulthood. 770 schoolchildren, ages 5–20 (mean age 12), 26-yr prospective follow-up. We categorized childhood and adult risk factors and 26-year changes (triglycerides [TG], LDL cholesterol, BMI, blood pressure [BP] and glucose ≥, and HDL cholesterol < pediatric and young adult cutoffs). These risk factors and race, cigarette smoking, and family history of CVD and T2DM were assessed as predictors of CVD and T2DM at mean age 38. Children who had high TG and retained high TG as adults had increased CVD events as adults (p = .0005). Children who had normal BMI and retained normal BMI as adults had reduced CVD events as adults (p = .02). Children who had high BP or high TG and retained these as adults had increased T2DM as adults (p = .0006, p = .003). Risk factors for CVD and T2DM retained from childhood to adulthood predict CVD and T2DM in young adulthood and support universal childhood screening.

Prospective, multicenter European study of the GORE flow reversal system for providing neuroprotection during carotid artery stenting.

Abstract: Background: Embolic protection devices (EPDs) are used to provide protection against brain embolization during carotid artery stenting (CAS) to treat carotid artery stenosis, but the optimal type of EPD has not been determined. Distally positioned filters are commonly used but do not provide protection during crossing of the lesion. This prospective, multicenter study investigated a proximally placed device (GORE Flow Reversal System) that reverses blood flow in the internal carotid artery during CAS, thereby directing emboli away from the brain. Methods: Outcomes in 122 patients (28% symptomatic), who underwent CAS using the flow reversal system were assessed (intention-to-treat analysis). The primary endpoint was a major adverse event (MAE; defined as death or stroke) within 30 days of CAS. The secondary endpoint was a myocardial infarction (MI) or nonstroke-related neurologic event within 30 days. Results: The flow reversal system could not be used in one patient because of severe vessel tortuosity and in two patients (1.6%) because of intolerance. The 30-day MAE rate and the secondary endpoint rate were each 1.6%. No patient in the series died or had an MI within 30 days. No patient who was symptomatic before CAS had an MAE. One symptomatic and one asymptomatic patient had a transient ischemic attack. Conclusions: Use of the GORE Flow Reversal System during CAS had a high rate of technical success and low 30-day rates of adverse neurologic and cardiac events. V C 2012 Wiley Periodicals, Inc.

Thrombophilia and retinal vascular occlusion

Abstract: Purpose The purpose of this research was to assess associations of thrombophilia with central retinal vein occlusion (CRVO), central retinal artery occlusion (CRAO), and amaurosis fugax (AF); to evaluate outcomes of normalizing high homocysteine; and to study CRVO, CRAO, and AF developing in estrogens/estrogen agonists in women subsequently shown to have thrombophilia. Methods Measures of thrombophilia-hypofibrinolysis were obtained in 132 CRVO cases, 15 CRAO cases, and 17 AF cases. Cases were compared to 105 healthy control subjects who did not differ by race or sex and were free of any ophthalmologic disorders. All cardiovascular disease (CVD) risk factors were compared to healthy general populations. Main outcome measures The main outcome measure of this study was thrombophilia. Results CRVO cases were more likely than controls to have high homocysteine (odds ratio [OR] 8.64, 95% confidence intervals [CI]: 1.96-38), high anticardiolipin immunoglobulin M (IgM; OR 6.26, 95% CI: 1.4-28.2), and high Factor VIII (OR 2.47, 95% CI: 1.31-7.9). CRAO-AF cases were more likely than controls to have high homocysteine (OR 14, 95% CI: 2.7-71.6) or the lupus anticoagulant (OR 4.1, 95% CI: 1.3-13.2). In four of 77 women with CRVO (two found to have high homocysteine, two with inherited high Factor XI), CRVO occurred after starting estrogen-progestins, estrogen-testosterone, or estrogen agonists. In one of eight women with CRAO found to have high anticardiolipin antibody IgG, CRAO occurred after starting conjugated estrogens, and AF occurred after starting conjugated estrogens in one of eleven women with AF (inherited protein S deficiency). Therapy for medians of 21 months (CRVO) and 6 months (CRAO-AF) was 5 mg folic acid, 100 mg B6, and 2000 mcg/day B12 normalized homocysteine in 13 of 16 (81%) CRVO cases and all five CRAO-AF cases with pretreatment hyperhomocysteinemia. The CRVO cases had an excess of hypertension; CRAO-AF cases had an excess of type 2 diabetes and hypertension. Conclusion Treatable thrombophilia, hyperhomocysteinemia in particular, is more common in RVO cases than in normal controls. RVO occurs after estrogens or estrogen agonists were administered in women subsequently shown to have thrombophilia.

Negative and positive predictive values of nerve monitoring in thyroidectomy

Abstract: Background Recurrent nerve injury is 1 of the most important complications of thyroidectomy During the last decade, nerve monitoring has gained increasing acceptance in several centers as a method to predict and to document nerve function at the end of the operation We evaluated the efficacy of a nerve monitoring system in a series of patients who underwent thyroidectomy and critically analyzed the negative predictive value (NPV) and positive predictive value (PPV) of the method Methods NIM System efficacy was prospectively analyzed in 447 patients who underwent thyroidectomy between 2001 and 2008 (366 female/81 male; 420 white/47 nonwhite; 11 to 82 years of age; median, 43 years old) There were 421 total thyroidectomies and 26 partial thyroidectomies, leading to 868 nerves at risk The gold standard to evaluate inferior laryngeal nerve function was early postoperative videolaryngoscopy, which was repeated after 4 to 6 months in all patients with abnormal endoscopic findings Results At the early evaluation, 858 nerves (988%) presented normal videolaryngoscopic features after surgery Ten paretic/paralyzed nerves (12%) were detected (2 unexpected unilateral paresis, 2 unexpected bilateral paresis, 1 unexpected unilateral paralysis, 1 unexpected bilateral paralyses, and 1 expected unilateral paralysis) At the late videolaryngoscopy, only 2 permanent nerve paralyses were noted (02%), with an ultimate result of 998% functioning nerves Nerve monitoring showed absent or markedly reduced electrical activity at the end of the operations in 25/868 nerves (29%), including all 10 endoscopically compromised nerves, with 15 false-positive results There were no false-negative results Therefore, the PPV was 400%, and the NPV was 100% Conclusions In the present series, nerve monitoring had a very high PPV but a low NPV for the detection of recurrent nerve injury © 2011 Wiley Periodicals, Inc Head Neck, 2012

Early assessment of malignant lung nodules based on the spatial analysis of detected lung nodules

Abstract: We propose a novel approach for diagnosing malignant lung nodules based on analyzing the spatial distribution of Hounsfield values for the detected lung nodules. Spatial distribution of image intensities (or Hounsfield values) comprising the malignant nodule appearance is accurately modeled with a new rotationally invariant second-order Markov-Gibbs Random Field (MGRF). In this paper, we introduce a new maximum likelihood estimation approach to estimate the neighborhood system of the proposed rotation invariant MGRF and its potentials from a training set of nodule images with normalized intensity ranges. Preliminary experiments on 327 lung nodules (153 malignant and 174 benign) resulted in the 91.1% correct classification (for the 95% confidence interval), showing the proposed method is a promising supplement to current technologies (biopsy-based diagnostic systems) for the early diagnosis of lung cancer.

A founder BRCA2 mutation in non-Afrikaner breast cancer patients of the Western Cape of South Africa.

Abstract: Founder mutations in BRCA1 and BRCA2 have been reported in many different populations. We studied 105 Coloured and 16 Black Xhosa women residing in the Western Cape of South Africa diagnosed with breast cancer. We screened these patients using our standard panel of six previously reported SA Afrikaner and Ashkenazi Jewish BRCA1/2 mutations and identified only two Afrikaner mutations. Further screening by the protein truncation test (BRCA1 exon 11, and BRCA2 exons 10 and 11) revealed an additional four deleterious mutations (BRCA1 c.1504_ 1508del,p.Leu502AlafsX2, BRCA2 c.2826_2829del,p.Ile943LysfsX16, c.6447_6448dup,p.Lys2150IlefsX19 and c.5771_5774del,p.Ile1924Argfs X38). The latter, also known in Breast Cancer Information Core nomenclature as 5999del4, was identified in 4 of 105 (3.8%) Coloureds and 4 of 16 (25%) Xhosa women, which makes it a frequent founder mutation in the Western Cape Province. Although this mutation was previously reported to occur in the Netherlands, haplotype analysis indicated two distinct origins for the Dutch and South African mutations, excluding the possibility of a common Dutch ancestor and suggesting gene flow from the indigenous tribes such as the Xhosa to the Coloured population instead. Further studies to determine the carrier rate of this variant in the Xhosa and other SA populations are warranted.

Cell Therapy with Human Renal Cell Cultures Containing Erythropoietin-Positive Cells Improves Chronic Kidney Injury

Abstract: New therapeutic strategies for chronic kidney disease (CKD) are necessary to offset the rising incidence of CKD and donor shortage. Erythropoietin (EPO), a cytokine produced by fibroblast-like cells in the kidney, has recently emerged as a renoprotective factor with anti-inflammatory, antioxidant properties. This study (a) determined whether human renal cultures (human primary kidney cells [hPKC]) can be enriched in EPO-positive cells (hPKC(F+)) by using magnetic-bead sorting; (b) characterized hPKC(F+) following cell separation; and (c) established that intrarenal delivery of enriched hPKC(F+) cells would be more beneficial in treatment of renal injury, inflammation, and oxidative stress than unsorted hPKC cultures in a chronic kidney injury model. Fluorescence-activated cell sorting analysis revealed higher expression of EPO (36%) and CD73 (27%) in hPKC(F+) as compared with hPKC. After induction of renal injury, intrarenal delivery of hPKC(F+) or hPKC significantly reduced serum creatinine, interstitial fibrosis in the medulla, and abundance of CD68-positive cells in the cortex and medulla (p < .05). However, only hPKC(F+) attenuated interstitial fibrosis in the renal cortex and decreased urinary albumin (3.5-fold) and urinary tubular injury marker kidney injury molecule 1 (16-fold). hPKC(F+) also significantly reduced levels of renal cortical monocyte chemotactic protein 1 (1.8-fold) and oxidative DNA marker 8-hydroxy-deoxyguanosine (8-OHdG) (2.4-fold). After 12 weeks, we detected few injected cells, which were localized mostly to the cortical interstitium. Although cell therapy with either hPKC(F+) or hPKC improved renal function, the hPKC(F+) subpopulation provides greater renoprotection, perhaps through attenuation of inflammation and oxidative stress. We conclude that hPKC(F+) may be used as components of cell-based therapies for degenerative kidney diseases.

Appearance-based diagnostic system for early assessment of malignant lung nodules

Abstract: A novel 2D approach for early assessment of malignant lung nodules based on analyzing the spatial distribution of Hounsfield values for the detected lung nodules is proposed. Spatial distribution of Hounsfield values comprising the malignant nodule appearance is accurately modeled with a new 2D rotationally invariant second-order Markov-Gibbs Random Field (MGRF). Preliminary experiments on 109 lung nodules (51 malignant and 58 benign) show that the proposed method is a promising supplement to current technologies (biopsy-based diagnostic systems) for the early diagnosis of lung cancer.

Incunabular Immunological Events in Prion Trafficking

Abstract: While prions probably interact with the innate immune system immediately following infection, little is known about this initial confrontation. Here we investigated incunabular events in lymphotropic and intranodal prion trafficking by following highly enriched, fluorescent prions from infection sites to draining lymph nodes. We detected biphasic lymphotropic transport of prions from the initial entry site upon peripheral prion inoculation. Prions arrived in draining lymph nodes cell autonomously within two hours of intraperitoneal administration. Monocytes and dendritic cells (DCs) required Complement for optimal prion delivery to lymph nodes hours later in a second wave of prion trafficking. B cells constituted the majority of prion-bearing cells in the mediastinal lymph node by six hours, indicating intranodal prion reception from resident DCs or subcapsulary sinus macrophages or directly from follicular conduits. These data reveal novel, cell autonomous prion lymphotropism, and a prominent role for B cells in intranodal prion movement.

Employment outcomes following successful renal transplantation.

Abstract: Eng M, Zhang J, Cambon A, Marvin MR, Gleason J. Employment outcomes following successful renal transplantation. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01441.x. © 2011 John Wiley & Sons A/S. Abstract: Background: Data on employment outcomes after successful renal transplantation are few. We conducted this study to identify favorable factors for employment after transplantation. Methods: Adult patients <65 yr of age who underwent renal transplantation between January 1, 2002 and December 31, 2007 were surveyed. Patients with graft survival <1 yr were excluded. We also tested their knowledge of Medicare coverage after transplantation. Data were analyzed using chi-squared and Fisher’s exact tests. p-Value <0.05 was considered statistically significant. Results: A 55% response rate was obtained where 56% of respondents were employed after transplantation. Race, marital status, previous transplant, and complicated post-operative course did not influence employment. Favorable factors include male gender (p = 0.04), younger age (<40 [p = 0.0003] or <50 yr [p < 0.0001]), having ≥1 dependent (p = 0.04), higher education (minimum high school degree [p = 0.003] or some college [p = 0.002]), live donor recipient (p = 0.004), wait time <2 yr (p = 0.03), dialysis <2 yr (p < 0.0001) or pre-dialysis (p = 0.04), and pre-transplantation employment (p < 0.0001). Mean time for employment was 4.9 ± 6.3 months (median three months). Common reasons for unemployment were disability (59%) and retirement (27%). Finally, 7% correctly responded that Medicare benefits end 36 months following transplantation. Conclusions: Potentially modifiable factors to improve employment are earlier referral and better education regarding Medicare eligibility.

Low bone mass and high material bone density in two patients with Loeys-Dietz syndrome caused by transforming growth factor beta receptor 2 mutations.

Abstract: Loeys-Dietz syndrome (LDS) is a rare autosomal-dominant connective tissue disorder caused by heterozygous mutations in the genes encoding transforming growth factor beta receptor 1 or 2 (TGFBR1 or TGFBR2). Although an association between LDS and osteoporosis has been reported, the skeletal phenotype regarding bone mass is not well characterized. Here, we report on two LDS patients with mutations in TGFBR2. Patient 1 was a 24-year-old man who had a total of three fractures involving the left radius, the left metacarpal, and the right femur. At the age of 14 years, lumbar spine areal bone mineral density Z-score was -4.0 and iliac bone histomorphometry showed elevated bone turnover (bone formation rate per bone surface: 91 µm³/µm²/year; age-matched control values 37 [10], mean [SD]) and mildly low trabecular bone volume per tissue volume (17.2%; age-matched control values 25.7 [5.3]). Bone mineralization density distribution (BMDD) in trabecular bone was increased (Ca(Peak) 22.70 wt% Ca; age-matched control values 21.66 [0.52]). Patient 2, a 17-year-old girl, suffered from diffuse bone pain but had not sustained fractures. At 14 years of age, her lumbar spine areal bone mineral density Z-score was -3.4. Iliac bone histomorphometry at that age confirmed low bone mass (bone volume to tissue volume 10.1%, same control values as above) and high bone turnover (bone formation rate per bone surface 70 µm³/µm²/year). BMDD in trabecular bone was significantly shifted toward increased mineralization (Ca(Peak) 22.36 wt% Ca). Thus, it appears that LDS can be associated with low bone mass and high bone turnover but increased matrix mineralization of trabecular bone.

Effectiveness of antioxidants (propolis, blueberry, vitamin E) associated with verapamil in the medical management of Peyronie's disease: a study of 151 cases.

Abstract: A total of 151 patients (age: 24-74 years, mean: 55 ± 10.3) diagnosed with Peyronie's disease were enrolled in a non-surgical treatment. In addition to medical histories and physical examinations, all patients underwent the following tests: penile ultrasound, IIEF questionnaire and photographic documentation. The penile curvature was measured by taking a photograph during maximum erection. All 151 patients were treated at different times and with different combinations of drugs, and afterwards, they were clinically studied and divided into five different treatment groups: 1st = verapamil (injection + iontophoresis) + vitamin E + topical diclofenac + blueberries; 2nd = verapamil (injection + iontophoresis) + vitamin E + topical diclofenac + propolis; 3rd = verapamil (injection) + vitamin E + topical Diclofenac; 4th = verapamil (iontophoresis) + vitamin E + topical diclofenac; 5th = verapamil (injection + iontophoresis) + topical diclofenac + blueberries + propolis. All patients were treated for 6 months after which they underwent the same follow-up tests as performed prior to the treatment. The following was achieved: group 1 had the most reduction in plaque size (-66.4%; p = 0.000), group 2 obtained the highest rate where penile curvature disappeared (24.5%; p = 0.019); the best results with reference to decrease in curvature angle were reached by the 2nd group (-14°) and group 1 obtained -9.6° (p = 0.000).

Anti-JC-virus antibody prevalence in a German MS cohort

Abstract: Dear Sir, The anti-JC-virus-IgG (anti-JCV) antibody status has been introduced to stratify patients with multiple sclerosis (MS) treated with natalizumab for the risk of developing progressive multifocal leukoencephalopathy (PML). We tested sera of 511 patients (360 females, 151 males) from 9 German MS centres for the anti-JCV antibody status applying the published protocol.1 The samples were either taken for the purpose of treatment decision making (e.g. treatment discontinuation, treatment initiation with natalizumab) or within the prospective German natalizumab pharmacovigilance study after obtaining written informed consent. This study was approved by the local ethical committees at the different sites. The overall seroprevalence in our German cohort was 56%, and there was no significant sex difference (females 55%, males 58%, Figure 1A). The seropositivity rate gradually increased with age, from 37% in patients younger than 20 years to 77% in patients at the age of 60 years or beyond (Figure 1B). Our data independently confirm the published data in other cohorts, applying the same methodology.1, 2 The observed increase in seropositivity with age, fitting a reported annual seroconversion rate for anti-JCVantibody status ranging between 2% and 3%,1 strongly argues for a close clinical and serological follow-up of patients tested negative for anti-JCV antibodies when applying the test to stratify patients for the risk of developing PML in clinical practice. In addition, we studied six patients with PML from our cohort prior to (n = 3) or at the time of PML diagnosis (n = 3). All of these patients tested positive for anti-JCV antibodies. All non-PML patients with detectable JCVDNA in serum (1 of 33 tested) or urine (3 of 18 tested) also tested positive for anti-JCV antibodies, supporting the potential utility of this method: no false-negative results were observed. However, no firm conclusions, such as risk calculations, can be drawn from these data as the number of patients with PML included was too low. Long-term observational studies are on the way to prospectively correlate the JCV antibody positivity and the development of PML during treatment with natalizumab.3 In the meantime the test might already be a useful tool to assist in treatment decisions in a proportion of patients.4 Nevertheless, high clinical and paraclinical vigilance for signs of severe 429955 MSJ18710.1177/1352458511429955Warnke et al.Multiple Sclerosis Journal 2012

Posterior Interosseous Artery Distal Radius Graft for Ulnar Nonunion Treatment

Abstract: The aim of our study was to describe a dorsal distal radius vascularized bone graft pedicled on the posterior interosseous artery (PIA), and its clinical application in 2 cases of ulnar nonunion. We studied the surgical technique in 5 freshly injected cadavers. The 4th extensor compartment artery originates from the anastomotic arch between the posterior division of the anterior interosseous artery and the PIA and provides periosteal branches to supply the dorsal distal radius metaphysis. A 2-cm vascularized bone graft can be harvested from the radius, and dissection of the PIA enables a long pedicle with a wide arc of rotation able to reach the ulnar diaphysis. The approach is limited to the forearm and distal radius and has minimal donor morbidity.

Titrating lovaza from 4 to 8 to 12 grams/day in patients with primary hypertriglyceridemia who had triglyceride levels >500 mg/dl despite conventional triglyceride lowering therapy

Abstract: Omega-3 fatty acids are important in treatment of severe primary hypertriglyceridemia (HTG). In 15 patients with severe primary HTG (TG >500 mg/dl despite conventional TG lowering therapy), we assessed efficacy-safety of sequential monthly treatment with Lovaza, 4 to 8 to 12 g/day. With TG >500 mg/dl despite Type V diet, hyperinsulinemia and diabetes control, and fibric acids, Lovaza (4 g/d) was added for 1 month, and if TG remained >500 mg/dl, increased to 8 g/d for 1 month, and then to 12 g/d for 1 month, and subsequently reduced to 4 g/day for 4 months. Primary HTG, median TG 884 mg/dl, 14 men, 1 woman, all white, age 50 ± 7 years, 12 non-diabetic, 3 with stable diabetes control. Weight and diet held stable throughout. In 5 patients, after 1, 2, and 3 months on 4 g/day, TG fell <500, mean 1390 to 234 (−83%, p<.0001), to 135 (−90%, p<.0001), and 158 mg/dl (−89%, p<.0001), with a negative TG slope, p=.0013. Non-HDLC fell from 320 to 177 (−45%, p=.001), to 152 (−53%, p=.0002), and to 163 (−49%, p=.0004), with a negative slope, p=.01. In 10 patients, with Lovaza increased from 4 to 8 to 12 g, 3 failed to respond. In 7 of these 10 patients, TG fell 37% from 1075 to 672 on 4 g (p=.006), to 577 on 8 g (−46%, p=.0009), and to 428 mg/dl (−60%, p<.0001) on 12 g/day, with a negative TG slope, p=.0018. TG on 12 g/day was lower than on 8 g/day, p =.03. Non-HDLC fell from 245 to 217 mg/dl (−11%) on 4 g/day, to 203 (−17%, p=.01) on 8 g/day, and to 192 (−22%, p=.003) on 12 g/day, with a negative slope, p=.016. Compared to pre-Lovaza baseline, no abnormal measures developed in safety tests. The 4, 8, and 12 g/d Lovaza doses were well tolerated. Titration of Lovaza from 4 to 8 to 12 g/d safely offers an effective way to lower TG beyond conventional 4 g therapy.

Determinants of ApoB, ApoA1, and the ApoB/ApoA1 ratio in healthy schoolgirls, prospectively studied from mean ages 10 to 19 years: the Cincinnati National Growth and Health Study.

Abstract: The objectives were to prospectively assess determinants of apolipoproteins B (ApoB), A1 (ApoA1), and the ApoB/ApoA1 ratio in 797 healthy black and white schoolgirls from mean ages 10 to 19. There was prospective 9-year follow-up, with measures of ApoB at mean ages 10, 12, 14, 16 and 19, ApoA1 at mean ages 12, 14, 16, and 19, and assessment of annual reports of delayed menstrual cyclicity (≥42 days) from ages 14 to 19. Studies of 402 black and 395 white healthy schoolgirls were done in public and private schools, in urban and suburban Cincinnati. Black girls had lower ApoB, higher ApoA1, and lower ApoB/ApoA1. SHBG at age 14 in white and black girls was inversely correlated with the ApoB/ApoA1. At age 19, ≥3 annual reports of menstrual delay ≥42 days and metabolic syndrome were associated with higher ApoB and a higher ApoB/ApoA1 ratio. From ages 14 to 19, BMI and TG were independently positively associated with ApoB. Menstrual cyclicity ≥42 days, metabolic syndrome, BMI, and TG were independently positively associated with ApoB/ApoA1 ratios, while black race was negatively associated. The atherogenic ApoB/ApoA1 ratio from ages 14 to 19 is lower in black girls, and positively associated with hyperandrogenism, menstrual cyclicity ≥42 days, BMI, TG, and the metabolic syndrome, facilitating an adolescent approach to primary prevention of cardiovascular disease.

A biomarker for severity of Alzheimer's disease: 1H-NMR resonances in cerebrospinal fluid correlate with performance in mini-mental-state-exam.

Abstract: Context: There is no valid biomarker for severity of Alzheimer’s disease (AD) available until now.Objective: Therefore, we investigated 1H-NMR spectroscopy for specific resonances as biomarkers for severity of AD.Materials and methods: Cerebrospinal fluid (CSF) of patients with diagnosed AD and healthy control subjects was analysed by one-dimensional water-suppressed 1H-NMR spectroscopy. The resonances were correlated with the cognitive performance of the patients and controls.Results: Specific 1H-NMR resonances showed higher intensities in AD patients than in control subjects. Mini-mental-state-exam scores correlated with 1H-NMR resonances in AD patients.Discussion and conclusion: 1H-NMR resonances of CSF are obviously valid biomarker for severity of AD, despite the lack of knowledge of the underlying molecular structure. Successful isolation and identification of these substances will most likely provide details to the pathophysiology of AD.