Cerebral Palsy

OBJECTIVE: Using a combination of clinical, radiographic, functional, and serum protein biomarker assessments, this study was aimed at defining the prevalence and clinical characteristics of interstitial lung disease (ILD) in a large cohort of patients with anti-Jo-1 antibodies. METHODS: A review of clinical records, pulmonary function test results, and findings on imaging studies determined the existence of ILD in anti-Jo-1 antibody-positive individuals whose data were accumulated in the University of Pittsburgh Myositis Database from 1982 to 2007. Multiplex enzyme-linked immunosorbent assays (ELISAs) for serum inflammation markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups were performed to assess the serum proteins associated with anti-Jo-1 antibody-positive ILD. RESULTS: Among the 90 anti-Jo-1 antibody-positive individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met the criteria for ILD. While computed tomography scans revealed a variety of patterns suggestive of underlying usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia, a review of the histopathologic abnormalities in a subset of patients undergoing open lung biopsy or transplantation or whose lung tissue was obtained at autopsy (n = 22) demonstrated a preponderance of UIP and diffuse alveolar damage. Analysis by multiplex ELISA yielded statistically significant associations between anti-Jo-1 antibody-positive ILD and elevated serum levels of C-reactive protein (CRP), CXCL9, and CXCL10, which distinguished this disease entity from idiopathic pulmonary fibrosis and anti-signal recognition particle antibody-positive myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these disease subgroups at high levels of sensitivity and specificity. CONCLUSION: In this large cohort of anti-Jo-1 antibody-positive individuals, the incidence of ILD approached 90%. Multiplex ELISA demonstrated disease-specific associations between anti-Jo-1 antibody-positive ILD and serum levels of CRP as well as the interferon-gamma-inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD.

Endothelial monocyte-activating polypeptide-II (EMAP-II) appears to play an important role in neovascularization and endothelial abnormalities. However, the role of EMAP-II in development of graft-versus-host disease (GVHD) after allogeneic SCT is poorly understood. We measured and compared the levels of EMAP-II, cytokines, and soluble factors in patients undergoing allogeneic SCT. The subjects were 23 patients who underwent allogeneic SCT. Most of the cytokines/soluble factors exhibited a significant elevation after allogeneic SCT, although Angiopoietin-1 did not change. On the other hand, the levels of these factors did not change significantly in the recipients of autologous SCT. When the relationship between EMAP-II and cytokines/soluble factors was analyzed, EMAP-II levels correlated positively with sIL-2R, sVCAM-1, sE-selectin, sFasL and EDMP. However, IL-6, Angiopoietin-1, Angiopoietin-2 and VEGF were not correlated with EMAP-II. Our results suggest that EMAP-II plays an important role in endothelial cell dysfunction related to GVHD after allogeneic SCT.

Aims. This study was performed to evaluate the relationship between three different natriuretic peptides and left ventricular mass, function and diameter, and kidney function in patients with hypertension. Methods. One hundred and thirty-nine patients with moderate hypertension were consecutively included. N-terminal brain natriuretic peptide (Nt-BNP), brain natriuretic peptide (BNP) and N-terminal pro-atrial natriuretic peptide (Nt-ANP) were analyzed. Cardiac remodeling was assessed by echocardiography (UCG) and glomerular filtration was estimated by cystatin C. Results. Patients were stratified into four groups with regard to the extent of cardiac remodeling: (1) no remodeling; (2) one of left ventricular hypertrophy, left ventricular dysfunction or left ventricular dilatation; (3) two of above and (4) all three parameters. All peptides differed significantly between the groups (all p<0.001), with a continuous stepwise increase from groups 1 through 4. Receiver operating characteristic analysis showed equal diagnostic performances for the detection of any cardiac abnormalities for Nt-BNP [area under curve, AUC= 0.63 (0.52-0.75), p= 0.026] and BNP [AUC= 0.64 (0.53-0.76), p= 0.019], both, however superior to Nt-ANP [AUC=0.59 (0.47-0.70), p= 0.139]. In multivariable linear regression analysis, all three indicators of cardiac remodeling were independently correlated with ln Nt-BNP and ln BNP, whereas only left ventricular diameter was independently correlated with ln Nt-ANP. Conclusions. Natriuretic peptide levels increased with increasing number of markers of cardiac remodeling. Nt-BNP and BNP are useful to discriminate between patients with regard to cardiac remodeling and might be considered a screening tool in order select patients eligible for further examination with UCG examination.

Background aims Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by an accelerated destruction of platelets as a result of the presence of autoreactive antibodies. Patients with ITP also display activated platelet-autoreactive T cells. Mesenchymal stem cells (MSC) inhibit both T- and B-cell activation and may have functional impairments in autoimmune disorders. Methods We analyzed the potential role of MSC in the pathogenesis of ITP. Results MSC from ITP showed an impaired proliferative capacity and a lower capability of inhibiting activated T-cell proliferation compared with healthy donors. While MSC from controls showed a decreased expression of p27 after stimulation with platelet-derived growth factor, this effect was not observed in MSC from patients. Furthermore, MSC from healthy donors down-regulated p16 upon exposure to platelet-released supernatant, while this effect was not observed for ITP. Interestingly, caspase 9 expression was higher in MSC from ITP. Conclusions These abnormalities suggest a role of MSC malfunction in the physiopathology of the disease and may have therapeutic implications.

SIL-TAL1 fusion gene and the ectopic expression of HOX11L2 are common molecular abnormalities in T-cell acute lymphoblastic leukemia (T-ALL). To verify their influence on outcome, we analyzed a Brazilian pediatric T-ALL series of cases. One hundred and ninety two children, age ranged 0-21 years old, were consecutively diagnosed and treated. Reverse transcriptase-polymerase chain reaction (RT-PCR) technique was used to identify the molecular alterations. Kaplan-Meyer method was applied to estimate overall survival. The most frequent maturation stage was T-IV (40.1%), and 30.7% of cases were CD10(+). SIL-TAL1(+) and HOX11L2(+) accounted for 26.7% and 10.3% of the cases, respectively. The overall survival (OS) was 74% in 80-month follow-up. HOX11L2(+) was not predictive factor for outcome. Considering patients younger than nine years-old, those with SIL-TAL1(+) presented a poorer outcome (p = 0.02). The results of this study suggest that in the Brazilian population only the presence of SIL-TAL1 can predict outcome in a restricted group of patients.

Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are important recalcitrant halogenated compounds that have been regarded as major environmental pollutants. Recently, their concurrent appearance in the environment and humans and their structural and toxicological profile similarities have sparked interest in the potential toxicologic consequences of their coexposure. The aim of the current study was to evaluate the cytogenotoxic effects induced by 2,2′,4,4′-tetrabromodiphenyl ether (PBDE-47) combined with 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) treatment in human neuroblastoma cells (SH-SY5Y) in vitro. SH-SY5Y cells were exposed to different concentrations of PBDE-47 (0, 2, 4, 8 muM) with or without PCB153 (5 muM) for 24 h. Thereafter, the cell viability, DNA damage, chromosomal abnormalities, and DNA-protein crosslinks (DPC) were determined. The results show that PBDE-47 and PCB153 alone and in combination induce DNA damage, with an increase in the frequency of micronuclei (MN) and DPC formation with increasing PBDE-47 concentration. In cells coexposed to PBDE-47 and PCB153, the cell viability significantly decreased while the MN frequency, DNA damage and DPC formation were all obviously increased compared to those of cells treated with the corresponding concentrations of PBDE-47 or PCB153 alone. Factorial analysis suggests that there were interactions between PBDE-47 and PCB153. The results imply that PBDE-47 interacts with PCB153 to inhibit cell viability and induce DNA damage, DPC formation, and chromosome abnormalities. (c) 2009 Wiley Periodicals, Inc. Environ Toxicol, 2009.

The PREDICT-HD study seeks to identify clinical and biological markers of Huntington’s disease in premanifest individuals who have undergone predictive genetic testing. We compared baseline motor data between gene-expansion carriers (cases) and nongene-expansion carriers (controls) using t-tests and Chi-square. Cases were categorized as near, mid, or far from diagnosis using a CAG-based formula. Striatal volumes were calculated using volumetric magnetic resonance imaging measurements. Multiple linear regression associated total motor score, motor domains, and individual motor items with estimated diagnosis and striatal volumes. Elevated total motor scores at baseline were associated with higher genetic probability of disease diagnosis in the near future (partial R(2) 0.14, P < 0.0001) and smaller striatal volumes (partial R(2) 0.15, P < 0.0001). Nearly all motor domain scores showed greater abnormality with increasing proximity to diagnosis, although bradykinesia and chorea were most highly associated with diagnostic immediacy. Among individual motor items, worse scores on finger tapping, tandem gait, Luria, saccade initiation, and chorea show unique association with diagnosis probability. Even in this premanifest population, subtle motor abnormalities were associated with a higher probability of disease diagnosis and smaller striatal volumes. Longitudinal assessment will help inform whether motor items will be useful measures in preventive clinical trials. (c) 2009 Movement Disorder Society.

The aim of this experiment is to understand how Parkinson’s disease (PD) medication affects the autonomic responses of individuals during an acute exercise stress test. Fourteen people with PD and fifteen healthy individuals age-matched between 50 and 80 years performed a modified Bruce protocol. Subjects with PD performed the test once off medication (PD-off) and then 1 week later on medication (PD-on). Heart rate (HR), blood pressure (BP), VO(2), and norepinephrine (NE) levels were taken at rest and at peak exercise. At peak exercise HR, BP, and NE values for the PD-on and PD-off group were all significantly lower than healthy controls, regardless of whether subjects were on their medication. Autonomic abnormalities during exercise in this population appear to be disease manifested and not impactedby medications used to treat PD. We can assume, both on and off medication, this population will show markedly lower BP, HR, and NE responses. (c) 2009 Movement Disorder Society.

Amiodarone is used commonly in patients with cardiac diseases. Common side effects include thyroid dysfunction and hepatic abnormalities. However, recently there has been concern for developing liver cirrhosis secondary to amiodarone therapy. We present two cases of liver cirrhosis in patients taking amiodarone. Their clinical presentation as well as histological features are discussed in detail.

Imprecise characterization of complaints of the upper and lower gastrointestinal (GI) tract puts patients at risks of either a delayed diagnosis or misdiagnosis and contributes to an increase in the overall direct and indirect costs of the health system. The current scenario in the case of functional GI diseases originates from at least two conditions: frequency of diseases and bothersome symptoms with an impact on the quality of life (QoL). To make a correct diagnosis is therefore almost mandatory. Once a positive diagnosis of functional involvement of the GI tract is made, the correct diagnosis assessment includes the study of symptom characteristics, entity and perception, detection of abnormal patterns of GI motor-function (gallblader and gastric emptying, oro-cecal and colonic transit, etc.), potential involvement of the autonomic nervous system (sympathetic, parasympathetic), and overall impact of such abnormalities on the QoL and psychological profiles. Results of these tests can be variable, depending on the type and intensity of the illness. In the present review, the state-of-the-art methods for correct assessment of several factors regarding the onset, perpetuation and outcome of functional GI diseases are discussed.