Methylmalonic acidemia caused by an l -methylmalonyl-CoA mutase deficiency. The mut0 type is associated with significant mortality and morbidity, but tandem mass spectrometry has made early detection ...possible. Five patients were identified through newborn screening for elevated propionylcarnitine (C3-carnitine) levels. These patients received a positive screening result at a median age of 10 days (range, 5-18 days). When treated at a median age of 11 days (range, 3-50 days), 2 patients were asymptomatic, and only one was significantly acidotic (pH <7.2), but all had various degrees of hyperammonemia (range, 127-1,244 μmol/L). Magnetic resonance imaging of the brain was performed in 4 patients shortly after diagnosis, and the results were all abnormal. Four patients were followed. There was no further metabolic decompensation after the initial episodes, but their mean developmental quotient was only 50. These results suggest that early hyperammonemia can lead to significant brain damage in methylmalonic acidemia. Therefore, treatment of this disease in newborns must be more aggressive.
Objectives The goal of this study is to characterize resident cardiac stem cells (CSCs) and investigate their therapeutic efficacy in myocardial infarction by molecular imaging methods. Background ...CSCs have been isolated and characterized in vitro. These cells offer a provocative method to regenerate the damaged myocardium. However, the survival kinetics and function of transplanted CSCs have not been fully elucidated. Methods CSCs were isolated from L2G85 transgenic mice (FVB strain background) that constitutively express both firefly luciferase and enhanced green fluorescence protein reporter gene. CSCs were characterized in vitro and transplanted in vivo into murine infarction models. Multimodality noninvasive imaging techniques were used to assess CSC survival and therapeutic efficacy for restoration of cardiac function. Results CSCs can be isolated from L2G85 mice, and fluorescence-activated cell sorting analysis showed expression of resident CSC markers (Sca-1, c-Kit) and mesenchymal stem cell markers (CD90, CD106). Afterwards, 5 × 105 CSCs (n = 30) or phosphate-buffered saline control (n = 15) was injected into the hearts of syngeneic FVB mice undergoing left anterior descending artery ligation. Bioluminescence imaging showed poor donor cell survival by week 8. Echocardiogram, invasive hemodynamic pressure-volume analysis, positron emission tomography imaging with fluorine-18-fluorodeoxyglucose, and cardiac magnetic resonance imaging demonstrated no significant difference in cardiac contractility and viability between the CSC and control group. Finally, postmortem analysis confirmed transplanted CSCs integrated with host cardiomyocytes by immunohistology. Conclusions In a mouse myocardial infarction model, Sca-1–positive CSCs provide no long-term engraftment and benefit to cardiac function as determined by multimodality imaging.
Background Large anterior choroidal artery (AChA) infarcts are frequently associated with stroke evolution. This study aimed to investigate the major determinants for stroke evolution in patients ...with large AChA infarcts. Methods We studied 118 consecutive adult patients with acute large AChA infarcts. The diagnosis was confirmed as abnormal hyperintensities in 3 or more rostracaudal magnetic resonance imaging slices (5 mm thickness) using diffusion-weighted imaging within typical AChA vascular regions. Stroke evolution was defined as neurologic deterioration with an increase in National Institutes of Health Stroke Scale (NIHSS) score by at least 4 or an increase of NIHSS score in motor function by at least 2 in 7 days after stroke onset. Results Forty-seven (39.8%) patients developed stroke evolution. Thrombolytic therapy was inversely associated with the occurrence of stroke evolution ( P = .004). Using multivariate analysis, thrombolytic therapy was the only protective determinant for stroke evolution (adjusted odds ratio, .08; 95% confidence interval, .01 to .67). Patients with large AChA infarcts receiving thrombolytic therapy had less unfavorable long-term functional outcome than those not receiving thrombolytic therapy (adjusted odds ratio, .11; 95% confidence interval, .02-.75). Conclusions Thrombolytic therapy is an only determinant factor for stroke evolution in large AChA infarcts, which reduced the risk of stroke evolution and improved functional outcome.
Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the drug hypersensitivity syndrome, ...Stevens-Johnson syndrome, and toxic epidermal necrolysis. The adverse events are unpredictable and carry significant morbidity and mortality. To identify genetic markers for allopurinol-SCAR, we carried out a case-control association study. We enrolled 51 patients with allopurinol-SCAR and 228 control individuals (135 allopurinol-tolerant subjects and 93 healthy subjects from the general population), and genotyped for 823 SNPs in genes related to drug metabolism and immune response. The initial screen revealed strong association between allopurinol-SCAR and SNPs in the MHC region, including BAT3 (encoding HLA-B associated transcript 3), MSH5 (mutS homolog 5), and MICB (MHC class I polypeptide-related sequence B) ($P<10^{-7}$). We then determined the alleles of HLA loci A, B, C, and DRB1. The HLA-B*5801 allele was present in all (100%) 51 patients with allopurinol-SCAR, but only in 20 (15%) of 135 tolerant patients odds ratio 580.3 (95% confidence interval, 34.4-9780.9); corrected P value=4.7× 10-24 and in 19 (20%) of 93 of healthy subjects 393.51 (23.23-6665.26); corrected P value=8.1× 10-18. HLA alleles A*3303, Cw*0302, and DRB1*0301 were in linkage disequilibrium and formed an extended haplotype with HLA-B*5801. Our results indicated that allopurinol-SCAR is strongly associated with a genetic predisposition in Han Chinese. In particular, HLA-B*5801 allele is an important genetic risk factor for this life-threatening condition.
Purpose To compare structural differences in the anterior chamber angle (ACA) and related optic components in children with or without retinopathy of prematurity (ROP). Design Prospective ...cross-sectional study. Methods Setting: A referred medical center in Taiwan. Study Population: The patients included preterm children with a history of ROP who had undergone laser therapy. The controls included age-matched healthy full-term children. Observation Procedure: The ACA structures were evaluated using gonioscopy. Main Outcome Measures: The angularity of the anterior chamber and associated anatomical changes. Results We examined 54 eyes of 29 preterm children with ROP and 134 eyes of 67 children born at term. The eyes of the ROP children exhibited a narrower ACA, steeper iris curvature, and more anteriorly inserted iris than those of the full-term children ( P < .001, = .002, and = .08, respectively). The eyes of the ROP children also exhibited steeper corneas, shallower anterior chamber depths, thicker lenses, and higher degrees of refractive errors (all P < .001) than those of the full-term children. The axial lengths (AL) did not differ between the two groups ( P = .15). Conclusions The eyes of the ROP children presented a narrower ACA and a more anteriorly curved and inserted iris than those of the full-term children. A steeper cornea, shallower anterior chamber, and greater lens thickness were the main structural changes in the anterior segment components of these patients. Further research is needed to investigate the association between these structural changes and the development of certain ocular diseases, such as glaucoma, in these patients.
Background & Aims: The association of Epstein–Barr virus (EBV) and gastric carcinomas (GCs) has been shown to vary among different populations and certain histological subtypes. Few studies have ...addressed the status of
Helicobacter pylori infection and genetic alterations in these EBV-positive or -negative GCs.
Methods: Eleven gastric lymphoepithelioma-like carcinomas (LELCs) and 139 cases of common non-LELCs were evaluated for the presence of EBV DNA using polymerase chain reaction (PCR) and RNA in situ hybridization.
H. pylori infection was determined by anti–
H. pylori immunoglobulin G in preoperative sera. Immunostaining for p53, c-erbB-2, and E-cadherin was performed. Microsatellite instability was analyzed by PCR using 10 primers.
Results: EBV was detected in 11 (100%) LELCs and in 19 (13.7%) of 139 common GCs. Compared with EBV-negative GCs, gastric LELCs tended to have a relatively higher frequency of proximal location, diffuse histological subtype, p53 overexpression, and reduced E-cadherin expression but a lower frequency of lymph node metastasis, previous
H. pylori infection, and c-erbB-2 overexpression. In contrast, no significant difference of clinicopathologic and genetic profiles was observed between EBV-positive non-LELC GCs and EBV-negative GCs. No correlation of microsatellite instability was found among these 3 subsets of GCs.
Conclusions: Dissecting clinicopathologic characteristics and infection status of EBV and
H. pylori provide additional evidence of etiological and genetic heterogeneity for GC. Distinct clinicopathologic and genetic pathways exist in gastric LELCs, in which EBV may play a more important role than
H. pylori infection.
GASTROENTEROLOGY 2000;118:1031-1038
Abstract Purposes This study's aim was to determine the predictive factors of the duration of first-attack acute urticaria in children. Basic Procedures The sample included 1075 children admitted to ...the emergency department with first-attack acute urticaria. Variables comprising the clinical features and past histories of children with duration of disease of 3 days or less, 4 to 7 days, 8 to 14 days, and 15 days or more were compared to determine the predictors of duration of acute urticaria. Main Findings Age, various etiologies, clinical presentations, coexistent pyrexia or angioedema, and personal histories of allergic diseases were significant factors (all P < .05). Among allergic diseases, atopic dermatitis was the most significant predictor of duration of acute urticaria, and those with multiple allergic diseases had longer durations of urticaria (both P < .05). Oral plus injection forms of antihistamine or steroid were related to shorter duration of disease ( P < .05). Principal Conclusions Etiologies and personal allergy history may be the most important predictors of the duration of a first attack of acute urticaria.
Abstract Background Previous studies suggested that epicardial patch applied to the infarcted site after acute myocardial infarction (MI) can alleviate left ventricular (LV) remodeling and improve ...cardiac performance; however, the effects of regional epicardial patch on chronic phase of LV remodeling remain unclear. Methods and Results We studied 20 pigs with MI induced by distal embolization and impaired LV ejection fraction (LVEF <45%) as detected by gadolinium-enhanced cardiac magnetic resonance imaging (MRI). Eight weeks post-MI, all animal underwent open chest procedure for sham surgery (control, n = 12) or patch implantation over the infarcted lateral LV wall (patch group, n = 12). In the patch group, +dP/dt increased and LV end-diastolic pressure decreased at 20 weeks compared with immediately post-MI and at 8 weeks ( P < .05), but not in the control group ( P > .05). As determined by cardiac MRI, LV end-diastolic and end-systolic volumes increased at 20 weeks compared with 8 weeks in both groups ( P < .05). However, the increase in LV end-diastolic volume (+14.1 ± 1.8% vs. +6.6 ± 2.1%, P = .015) and LV end-systolic volume (+12.1 ± 2.4% vs. −4.7 ± 3.7%, P = .0015) were significantly greater in the control group compared with the patch group. Furthermore, the percentage increase in LVEF (+17.3 ± 4.9% vs. +4.1 ± 3.9%, P = .048) from 8 to 20 weeks was significantly greater in the patch group compared with the control group. Histological examination showed that LV wall thickness at the infarct region and adjacent peri-infarct regions were significantly greater in the patch group compared with the control group ( P < .05). Conclusion Regional application of a simple, passive synthetic epicardial patch increased LV wall thickness at the infarct region, attenuated LV dilation, and improved LVEF and +dP/dt in a large animal model of MI.
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