No abstract

Trisomy 18 is the second most common autosomal trisomy in newborns. The birth prevalence of this disorder is approximately 1 in 3,000 to 1 in 8,000, and the life span of the majority of patients is less than 1 year. As information regarding outcome in trisomy 18 is rather fragmentary in the literature, this study is aimed at investigating the survival and natural history of trisomy 18. We also evaluated the survival age and management of trisomy 18 in two different periods, before and after the implementation of National Health Insurance (NHI) program. Thirty-nine cases of trisomy 18 were collected in Mackay Memorial Hospital in a 17-year period, from 1988 to 2004. Delivery data, survival age, management before and after the implementation of NHI program, structural defects, image findings and cytogenetic results were analyzed by medical and nurse's records.

Globoid-cell leukodystrophy (GLD) is a rapidly progressing inherited neurodegenerative disorder caused by a deficiency in galactosylceramidase activity. Previous studies in the murine model of GLD (Twitcher mouse) have shown that both bone marrow transplantation (BMT) and central nervous system (CNS)-directed gene therapy can be moderately effective at ameliorating certain aspects of GLD. As BMT and CNS-directed gene therapy target fundamentally different tissues, we tested the hypothesis that combining these disparate therapies would be more efficacious than either therapy alone. Mice receiving myeloreductive conditioning at birth followed by syngeneic BMT had approximately 25-35% donor chimerism. Untreated Twitcher mice, Twitcher mice treated with BMT alone, AAV2/5 alone, or a combination of BMT and AAV2/5 had mean lifespans of 39, 44, 49, and 104 days, respectively. Twitcher mice treated with a combination of BMT and AAV2/5 also had significantly improved performance in several behavioral tests and greater reduction in demyelination, astrocytosis, and macrophage infiltration compared to untreated Twitcher mice or mice that received either therapy alone. These data suggest that CNS-directed gene therapy synergizes with BMT. The combination of these disparate therapeutic approaches may form the basis for more effective treatment of this inherited neurodegenerative disorder.

ABSTRACT. Objective. To assess the usefulness of laboratory parameters, including peripheral white blood cell (WBC) count, C-reactive protein (CRP) concentration, erythrocyte sedimentation rate (ESR), and microscopic urinalysis (UA), for identifying febrile infants younger than 8 weeks of age at risk for urinary tract infection (UTI), and comparison of standard UA and hemocytometer WBC counts for predicting the presence of UTI.Methods. A total of 162 febrile children <8 weeks of age were enrolled in this prospective study. All underwent clinical evaluation and laboratory investigation, including WBC count and differential; ESR; CRP; blood culture; a lumbar puncture for cell count and differential, glucose level, protein level, Gram stain, and culture; and a UA and urine culture. All urine specimens were obtained by suprapubic aspiration and microscopically analyzed with standard UA as well as with hemocytometer WBC counts. Quantitative urine cultures were performed. Sensitivity, specificity, accuracy, likelihood ratios, and receiver operating characteristic (ROC) curves were determined for each of the screening tests.Results. There were 22 positive urine culture results of at least 100 colony-forming unit/mL. Eighteen of these 22 patients were males, and all were uncircumcised. There were significant differences for pyuria м5 WBCs/ hpf, pyuria м10 WBC/L, CRP >20 mg/L, and ESR >30 mm/hour between culture-positive and culture-negative groups (P < .05). The ROC area for hemocytometer WBC count, standard UA, peripheral WBC count, ESR, and CRP concentration were .909 ؎ .045, .791 ؎ .065, .544 ؎ .074, .787 ؎ .060, and .822 ؎ .036, respectively. The ROC curve analysis indicates that the CRP, ESR, and standard UA were powerful but imperfect tools with which to discriminate for UTI in potentially infected neonates. Hemocytometer WBC counts had the highest sensitivity, specificity, accuracy, and likelihood ratios for identifying very young infants with positive urine culture results. For all assessments, hemocytometer WBC counts were significantly different, compared with the standard urinalysis. ESR, CRP, and peripheral WBC counts were not helpful in identifying UTI in febrile infants.Conclusion. UTI had a prevalence of 13.6% in febrile infants <8 weeks of age. The CRP, ESR, and standard UA were imperfect tools in discriminating for UTI, and the sensitivity of these laboratory parameters was relatively low. Hemocytometer WBC count was a significantly better predictor of UTI in febrile infants. Pediatrics 2000; 105(2). URL: http://www.pediatrics.org/cgi/content/full/ 105/2/e20; urinary tract infection, standard urinalysis, hemocytometer white blood cell counts, receiver operator characteristic curves.ABBREVIATIONS. UTI, urinary tract infection; UA, urinalysis; hpf, high-power microscopic field; WBC, white blood cell; CFU, colonyforming unit; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; MMH, Mackay Memorial Hospital; ROC, receiver operator characteristic curves; AUC, area under the curve; LR, likelihood ra...

Globoid-cell leukodystrophy (GLD) is an autosomal recessive lysosomal storage disorder caused by mutations in the galactosylceramidase (GALC) gene. Infantile GLD has a lethal course with severe cerebral demyelination that progresses to death by 2 years of age. In the current study twitcher mice, an authentic murine model of infantile GLD, were given intracranial injections of either recombinant adeno-associated virus serotype 2 encoding the murine Galc cDNA (AAV2-GALC) or the same genome pseudotyped with AAV5 capsid proteins (AAV2/5-GALC) on day 3 of age. The group injected intracranially with AAV2/5-GALC had approximately 25-fold greater than normal Galc levels in the brain, while AAV2-GALC-injected animals had 28% normal levels. The average life expectancy of twitcher mice ( approximately 38 days) was significantly (P < 0.0001) increased to 48 and 52 days for the AAV2-GALC- and AAV2/5-GALC-treated groups, respectively. The AAV2/5-GALC group performed significantly better in a battery of behavioral tests compared to untreated, AAV2-GFP-treated, or AAV2-treated twitcher animals. This longitudinal study demonstrated that AAV2/5-GALC-mediated gene therapy resulted in higher levels of Galc expression and slowed the neurologic deterioration more completely than AAV2-GALC in the murine model of globoid-cell leukodystrophy. However, the clinical improvements, as assessed by behavioral tests and life span, were only modest.

Early diagnosis and the survival patterns from the data collected should be used to inform parents and health-care professionals to assist in decision making. Although most patients with trisomy 13 die within the first weeks after birth, it is important to recognize that a few may survive the first year. When counseling families, the long-term survival prospects of trisomy 13 patients should be included.

To evaluate the prevalence of obstructive sleep apnea (OSA) and to clarify sleep characteristics in patients with mucopolysaccharidoses (MPS), we performed overnight polysomnographic studies in 24 patients (22 males and 2 females; 3 with MPS I, 15 with MPS II, 1 with MPS III, 1 with MPS IV, and 4 with MPS VI; mean age, 10.8 ± 6.0 years; age range, 2.0-23.7 years; 2 patients ≥18 years of age). The nadir arterial oxygen saturation (SaO(2) ) was 74.5 ± 12.3%, and the average percentage of sleep time with an SaO(2) of <95% was 39.4%. The percentages of total sleep time spent in sleep stages N1, N2, N3, and R were 18.6 ± 10.8%, 50.3 ± 7.6%, 14.8 ± 8.1%, and 15.3 ± 4.6%, respectively. The respiratory disturbance index (RDI) was 21.8 ± 20.4/hr, and obstructive apnea-hypopnea index (OAHI) and central apnea index were 21.4 ± 19.9/hr and 0.4 ± 0.6/hr, respectively. The desaturation index was 17.6 ± 17.8/hr. All patients had some degree of OSA. For 22 children, the disorder was mild (OAHI 1.5-5) in 2, moderate (OAHI 5-10) in 7, and severe (OAHI > 10) in 13. Two patients with MPS II who received enzyme replacement therapy had reductions in RDI after treatment (38.9-10.8 and 3.5-2.0, respectively). The prevalence of moderate to severe OSA was 88% (21/24) in patients with MPS. The overnight polysomnography will help to determine the abnormalities of breathing during sleep more precisely and urge the clinicians to take necessary action for patients with severe manifestations.

BackgroundObesity is a complex, multifactorial disorder influenced by the interaction of genetic, epigenetic, and environmental factors. Obesity increases the risk of contracting many chronic diseases or metabolic syndrome. Researchers have established several mammalian models of obesity to study its underlying mechanism. However, a lower vertebrate model for conveniently performing drug screening against obesity remains elusive. The specific aim of this study was to create a zebrafish obesity model by over expressing the insulin signaling hub of the Akt1 gene.Methodology/Principal Findings Skin oncogenic transformation screening shows that a stable zebrafish transgenic of Tg(krt4Hsa.myrAkt1)cy18 displays severely obese phenotypes at the adult stage. In Tg(krt4:Hsa.myrAkt1)cy18, the expression of exogenous human constitutively active Akt1 (myrAkt1) can activate endogenous downstream targets of mTOR, GSK-3α/β, and 70S6K. During the embryonic to larval transitory phase, the specific over expression of myrAkt1 in skin can promote hypertrophic and hyperplastic growth. From 21 hour post-fertilization (hpf) onwards, myrAkt1 transgene was ectopically expressed in several mesenchymal derived tissues. This may be the result of the integration position effect. Tg(krt4:Hsa.myrAkt1)cy18 caused a rapid increase of body weight, hyperplastic growth of adipocytes, abnormal accumulation of fat tissues, and blood glucose intolerance at the adult stage. Real-time RT-PCR analysis showed the majority of key genes on regulating adipogenesis, adipocytokine, and inflammation are highly upregulated in Tg(krt4:Hsa.myrAkt1)cy18. In contrast, the myogenesis- and skeletogenesis-related gene transcripts are significantly downregulated in Tg(krt4:Hsa.myrAkt1)cy18, suggesting that excess adipocyte differentiation occurs at the expense of other mesenchymal derived tissues.Conclusion/SignificanceCollectively, the findings of this study provide direct evidence that Akt1 signaling plays an important role in balancing normal levels of fat tissue in vivo. The obese zebrafish examined in this study could be a new powerful model to screen novel drugs for the treatment of human obesity.