Cerebral Palsy

Among autologous somatic stem cells, bone marrow-derived mesenchymal stem cells (BMSCs) are the most widely used worldwide to repair not only mesenchymal tissues (bone, cartilage) but also many other kinds of tissues, including heart, skin, and liver. Autologous BMSCs are thought to be safe because of the absence of immunological reaction and disease transmission. However, it is possible that they will form tumours during long-term follow-up. In 1988, we transplanted autologous BMSCs to repair articular cartilage, which was the first such trial ever reported. Subsequently we performed this procedure in about 40 patients. Demonstration that neither partial infections nor tumours appeared in these patients provided strong evidence for the safety of autologous BMSC transplantation. Thus, in this study we checked these patients for tumour development and infections. Between January 1998 and November 2008, 41 patients received 45 transplantations. We checked their records until their last visit. We telephoned or mailed the patients who had not visited the clinics recently to establish whether there were any abnormalities in the operated joints. Neither tumours nor infections were observed between 5 and 137 (mean 75) months of follow-up. Autologous BMSC transplantation is a safe procedure and will be widely used around the world. Copyright (c) 2010 John Wiley & Sons, Ltd.

PURPOSE: The aim of this study was to determine the prevalence of glaucomatous optic nerve atrophy among a working population in Germany by secondary evaluation of a study conducted to estimate the prevalence of retinal microangiopathic abnormalities by telemedical examination of the retina. PATIENTS AND METHODS: From August 2002 until January 2004 the retina and optic nerve head were examined in 19,294 Caucasians using a non-mydriatic fundus camera (Kowa, nonmyd-alpha 45), which produces colour images with 45 degrees. The images of the retina and optic nerve head were evaluated telemedically by glaucoma specialists in respect to optic nerve pathologies and microangiopathic abnormalities by a standardised procedure. Glaucomatous optic nerve atrophy was diagnosed when specific glaucomatous morphological alterations of the optic nerve head were present. A complete medical history including reported elevated intraocular pressure (IOP) and blood pressure was obtained. RESULTS: The intra-observer and inter-observer reliability were 0.884 and 0.740, respectively. Cronbach’s alpha for two evaluation cycles each of two observers was 0.870. The prevalences of glaucomatous optic nerve atrophy in the different age groups were 0.07 % (45 – 49 years), 0.40 % (50 – 54 years), 0.45 % (55 – 59 years) and 0.82 % (60 – 64 years). Age could be established as an important risk factor for glaucomatous optic nerve atrophy, while no influence of gender or family history was found. CONCLUSION: Telemedical evaluation of colour images of the retina and optic nerve acquired by a non-mydriatic fundus camera allows a fast and efficient screening of many subjects with medium reliability. © Georg Thieme Verlag KG Stuttgart · New York.

Hermansky Pudlak syndrome (HPS) is a heterogeneous recessive genetic disease with a tendency to develop lung fibrosis with aging. A mouse strain with two mutant HPS genes affecting separate vesicle trafficking pathways, C57BL/6-Hps1 ( ep )-Ap3b1 ( pe ), exhibits severe lung abnormalities at young ages, including enlarged alveolar type II (ATII) cells with giant lamellar bodies and foamy alveolar macrophages (AMs), which are readily identified histologically. In this study, the appearance of lung fibrosis in older animals was studied using classical histological and biochemical methods. The HPS double mutant mice, but not Chediak Higashi syndrome (C57BL/6-Lyst ( bg-J )-J, CHS) or C57BL/6J black control (WT) mice, were found to develop lung fibrosis at about 17 months of age using Masson trichrome staining, which was confirmed by hydroxyproline analysis. TGF beta1 levels were elevated in bronchial alveolar lavage samples at all ages tested in the double mutant, but not WT or CHS mice, indicative of a prefibrotic condition in this experimental strain; and AMs were highly positive for this cytokine using immunohistochemistry staining. Prosurfactant protein C staining for ATII cells showed redistribution and dysmorphism of these cells with aging, but there was no evidence for epithelial-mesenchymal transition of ATII cells by dual staining for prosurfactant C protein and alpha-smooth muscle actin. This investigation showed that the HPS double mutant mouse strain develops interstitial pneumonia (HPSIP) past 1 year of age, which may be initiated by abnormal ATII cells and exacerbated by AM activation. With prominent prefibrotic abnormalities, this double mutant may serve as a model for interventive therapy in HPS.

BACKGROUND: AML with myelodysplasia related changes (AML MRC) is known to show a poor prognosis compared with de novo AML, but controversies exist about the prognostic impact of multilineage dysplasia (MLD) among MRC. We investigated the prognostic impact of MLD in AML MRC. METHODS: A total of 357 patients newly diagnosed as AML at Asan Medical Center from January 2001 to December 2005 were analyzed. They were diagnosed and classified as AML with recurrent genetic abnormalities, AML MRC, and AML not otherwise specified (AML NOS). Prognostic markers including overall survival (OS) and event free survival (EFS) were obtained through retrospective analysis of electronic medical records. RESULTS: AML MRC patients showed a lower complete remission (CR) rate (44.7% vs. 64.9%, P=0.002) and shorter OS (297 vs. 561 days, P=0.004) and EFS (229 vs. 374 days, P=0.004) than AML NOS patients. Patients with MLD among AML MRC also showed a lower CR rate (37.7%, P=0.001) and shorter OS (351 days, P=0.036) and EFS (242 days, P=0.076) than AML NOS patients. However, among AML MRC patients, there were no differences in OS, EFS and CR between patients with and without MLD. CONCLUSIONS: AML MRC patients showed a lower CR rate and shorter OS and EFS than AML NOS patients. AML MRC patients with MLD showed similar results and their prognosis was not different from those without MLD. MLD findings among AML MRC could be an independent poor prognostic factor in de novo AML.

OBJECTIVE: The somatotropic axis (growth hormone [GH] and insulinlike growth factor I [IGFI]) play a role in the cognitive deficits seen with aging, GH deficiency, and neurodegenerative disorders such as Alzheimer disease. We recently reported elevations in basal plasma GH and IGFI levels in patients with Huntington disease (HD). Here, our objective was to determine whether somatotropic axis abnormalities predicted cognitive dysfunction in HD. METHODS: In this prospective cohort study of 109 patients with genetically documented HD, aged 21 to 85 years, we determined fasting blood levels of total IGFI, GH, and insulinlike factor binding protein 3 at baseline, and we used the cognitive Unified Huntington’s Disease Rating Scale to assess cognitive impairment at baseline and for up to 5 years subsequently. Associations were evaluated using mixed linear model analysis. RESULTS: Higher plasma IGFI concentrations were associated with greater cognitive decline (beta Stroop Words, -6.01, p = 0.003; beta Stroop Color, -4.41, p = 0.01; beta Stroop Color/Words, -3.86, p = 0.02; beta Symbol Digit Modalities, -3.69, p = 0.03; and beta verbal fluency, -5.01, p = 0.03). Higher free IGFI concentrations and higher GH concentrations in men also predicted greater cognitive decline. CONCLUSIONS: Our findings in patients with HD suggest that a high IGFI level at baseline may be associated with greater subsequent declines in executive function and attention.

CONTEXT: Conduct disorder (CD) is characterized by severe antisocial behavior that emerges in childhood (early-onset CD [EO-CD]) or adolescence (adolescence-onset CD [AO-CD]). Early-onset CD is proposed to have a neurodevelopmental basis, whereas AO-CD is thought to emerge owing to social mimicry of deviant peers. However, this developmental taxonomic theory is debated after reports of neuropsychological impairments in both CD subtypes. A critical, although unaddressed, issue is whether these subtypes present similar or distinct neurophysiological profiles. Hence, we investigated neurophysiological responses to emotional and neutral faces in regions associated with antisocial behavior (ie, the amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex) in individuals with EO-CD and AO-CD and in healthy control subjects. OBJECTIVE: To investigate whether EO-CD and AO-CD subjects show neurophysiological abnormalities. DESIGN: Case-control study. SETTING: Government research institute, university department. PARTICIPANTS: Seventy-five male adolescents and young adults aged 16 to 21 years, including 27 with EO-CD, 25 with AO-CD, and 23 healthy controls. Main Outcome Measure Neural activations measured by functional magnetic resonance imaging while participants viewed angry, sad, and neutral faces. RESULTS: Comparing angry vs neutral faces, participants with both CD subtypes displayed reduced responses in regions associated with antisocial behavior compared with controls; differences between the CD subtypes were not significant. Comparing each expression with fixation baseline revealed an abnormal (increased) amygdala response to neutral but not angry faces in both groups of CD relative to controls. For sad vs neutral faces, reduced amygdala activation was observed in EO-CD relative to AO-CD and control participants. Comparing each expression with fixation revealed hypoactive amygdala responses to sadness in individuals with EO-CD relative to AO-CD participants and controls. These findings were not accounted for by attention-deficit/hyperactivity disorder symptoms. CONCLUSIONS: Neurophysiological abnormalities are observed in both CD subtypes, contrary to the developmental taxonomic theory of CD. Additional amygdala hypofunction in relation to sad expressions might indicate why EO-CD is more severe and persistent than AO-CD.

Magnification, which is considered to be a relatively high “dose cost” mammographic technique, is a complementary examination performed on women exhibiting breast complaints or abnormalities. Particular attention is given to the imaging procedure as the primary aim is to confirm the existence of suspected abnormalities, despite the additional dose. The introduction of post-processing capabilities and the widespread use of digital mammography promoted some controversy in the last decades on whether electronic zoom performed on the derived initial screening mammogram can effectively replace this technique. This study used Monte Carlo simulation methods to derive simulated screening mammograms produced under several exposure conditions, aiming to electronically magnify and compare them to the corresponding magnification mammograms. Comparison was based on quantitative measurements of image quality, namely contrast to noise ratio (CNR) and spatial resolution. Results demonstrated that CNR was higher for geometric magnification compared to the case of electronic zooming. The percentage difference was higher for lesions of smaller radius and achieved 29% for 0.10 mm details. Although spatial resolution is maintained high in the zoomed images, when investigating microcalcifications of 0.05 mm radius or less, only with geometric magnification can they be visualised.

Background: Recent studies have revealed increased morbidity and mortality rates in term neonates without birth defects who were delivered before 39 weeks of completed gestation. We sought to determine if a similar association exists between gestational age at delivery and adverse outcomes in neonates with critical congenital heart disease, with particular interest in those born at 37 to 38 weeks' gestation. Patients and Methods: We studied 971 consecutive neonates who had critical congenital heart disease and a known gestational age and were admitted to our cardiac ICU from 2002 through 2008. Gestational age was stratified into 5 groups: >41, 39 to 40, 37 to 38, 34 to 36, and <34 completed weeks. Multivariate logistic regression analyses were used to evaluate mortality and a composite morbidity variable. Multivariate Poisson regression was used to evaluate duration of ventilation, intensive care, and hospitalization. Results: Compared with the referent group of neonates who were delivered at 39 to 40 completed weeks' gestation, neonates born at 37 to 38 weeks had increased mortality (6.9% vs 2.6%; adjusted P = .049) and morbidity (49.7% vs 39.7%; adjusted P = .02) rates and tended to require a longer duration of mechanical ventilation (adjusted P = .05). Patients born after 40 or before 37 weeks also had greater adjusted mortality rates, and those born before 37 weeks had increased morbidity rates and required more days of mechanical ventilation and intensive care. Conclusions: For neonates with critical congenital heart disease, delivery before 39 weeks' gestation is associated with greater mortality and morbidity rates and more resource use. With respect to neonatal mortality, the ideal gestational age for delivery of these patients may be 39 to 40 completed weeks.

Objective: To distinguish the effects of late preterm birth from the complications associated with the causes of delivery timing, this study used propensity score-matching methods on a statewide database that contains information on both mothers and infants. Methods: Data for this study came from Arkansas Medicaid claims data linked to state birth certificate data for the years 2001 through 2005. We excluded all multiple births, infants with birth defects, and infants at <33 weeks of gestation. Late preterm infants (LPIs) (34 to 36 weeks of gestation) were matched with term infants (37-42 weeks of gestation) according to propensity scores, on the basis of infant, maternal, and clinical characteristics. Results: A total of 5188 LPIs were matched successfully with 15303 term infants. LPIs had increased odds of poor outcomes during their birth hospitalization, including a need for mechanical ventilation (adjusted odds ratio [aOR]: 1.31 [95% confidence interval [CI]: 1.01-1.68]), respiratory distress syndrome (aOR: 2.84 [95% CI: 2.33-3.45]), and hypoglycemia (aOR: 1.60 [95% CI: 1.26-2.03]). Outpatient and inpatient Medicaid expenditures in the first year were both modestly higher (outpatient, adjusted marginal effect: $108 [95% CI: $58-$158]; inpatient, $597 [95% CI: $528-$666]) for LPIs. Conclusions: LPIs are at increased risk of poor health-related outcomes during their birth hospitalization and of increased health care utilization during their first year.

The majority of deaths in infants with hypoxic-ischemic encephalopathy (HIE) follow decisions to withdraw life-sustaining treatment. Clinicians use prognostic tests including MRI to help determine prognosis and decide whether to consider treatment withdrawal. A recently published meta-analysis provided valuable information on the prognostic utility of magnetic resonance (MR) biomarkers in HIE and suggested, in particular, that proton MR spectroscopy is the most accurate predictor of neurodevelopmental outcome. How should this evidence influence treatment-limitation decisions? In this article I outline serious limitations in existing prognostic studies of HIE, including small sample size, selection bias, vague and overly inclusive outcome assessment, and potential self-fulfilling prophecies. Such limitations make it difficult to answer the most important prognostic question. Reanalysis of published data reveals that severe abnormalities on conventional MRI in the first week have a sensitivity of 71% (95% confidence interval: 59%-91%) and specificity of 84% (95% confidence interval: 68%-93%) for very adverse outcome in infants with moderate encephalopathy. On current evidence, MR biomarkers alone are not sufficiently accurate to direct treatment-limitation decisions. Although there may be a role for using MRI or MR spectroscopy in combination with other prognostic markers to identify infants with very adverse outcome, it is not possible from meta-analysis to define this group clearly. There is an urgent need for improved prognostic research into HIE.