Studies of Caucasian and Japanese patients with insulin-dependent diabetes mellitus (IDDM) have shown that heterozygosity for certain HLA-DR antigens confers a high risk of developing the disease. The HLA antigens of 75 Chinese patients and 100 Chinese controls in Hong Kong were studied to investigate the role of HLA-DR heterozygosity in Chinese individuals. Some of the patients and controls were also tested for allotypic variation in the complement components C2, C4, and BF. Three alleles, Aw33, B17, and DR3, had increased frequencies in patients compared with controls and frequently occurred together in the same phenotype, which suggested their existence as a haplotype. There were no statistically significant differences in complement allotype frequencies between patients and controls, although the C4B null allele seemed to be associated with Aw33, B17, and DR3. No other HLA-DR antigen appeared to be associated with IDDM. However, when the patients were separated on the basis of age at onset, the frequency of DR3/DRw9 heterozygosity was markedly increased in patients presenting in the first decade of life, but there was no increase in patients presenting at greater than 20 yr of age. DRw9 is strongly associated with autoimmune disease in Chinese, whereas DR3 is not. We suggest that the major IDDM susceptibility locus in Chinese is associated with HLA-DR3 and that patients with HLA-DR3 and HLA-DRw9 have an added predisposition to autoimmune disease and therefore develop IDDM earlier than patients without DRw9.
Under pathological conditions in the adult CNS, such as ischemia, subarachnoid hemorrhage and Alzheimer's disease, endothelin (ET)-1- and -3-like immunoreactivities are elevated in astrocytes of the injured adult brain. However, it is not clear whether this is due to increased synthesis or increased binding of ET-1. Further, it is not known whether ET-1 expression is altered in the perinatal brain after cerebral hypoxia/ischemia (H/I). Here, we determined the sites of ET-1 expression in perinatal mouse brain after H/I injury by in situ hybridization using a probe specific for the ET-1 gene. Astrocyte-like cells, which do not normally express ET-1 mRNA, showed high levels of ET-1 mRNA expression. Endothelial cells of the capillaries and small vessels also showed an increased level of ET-1 mRNA. Our data suggest that ET-1 mRNA levels in the astrocyte-like cells and vascular endothelial cells are dynamically regulated by ischemia and may participate in perinatal ischemia-related neural damage.
Medulloblastoma is the most common malignancy of the central nervous system in childhood. With the current combined treatment with surgery, chemotherapy and radiotherapy, the survival rates had improved dramatically in recent years. However, these survivors are prone to develop various late sequelae secondary to treatment.
Purpose: To investigate the dosimetric accuracy of the sliding window gated IMRT compared with the static treatment, using varying dose rates.Materials and methods: This study measured changes in output and diode array response with changing dose rate, verified the precision of the motion table, and measured changes in dose distribution accuracy with film and diodes at two depths with changing dose rate.During 4DCT (4 Dimensional Computed Tomography), the patient's respiratory signals and target motion were recorded and imported to the XY4D simulation table of SUN NUCLEAR Corporation to simulate the patient's respiration and tumour motion.A single field of each sliding window IMRT plan with 30º wedge and one for lung cancer were used in this study.Three irradiating conditions, static and moving target with and without gating, were applied to both plans.Results: The standard deviations of output, with the dose rates changing from 300-600 MU/min, were 0.065 cGy and 0.169 cGy for the ionisation chamber and diode, respectively.The verification of the motion table shows very good precision with 9.98 ± 0.02 cm (true value = 10.0 cm).The measurements by MapCheck show the gamma index of the planned absolute dose distribution in static and moving targets with gating, resulting in more than 96% passing for all dose rates.The absolute dose distribution measured by film for the static target was agreeable with the value of moving target with gating. Conclusion:The sliding window gated IMRT technique is able to deliver an accurate dose to a moving target with the dose rate of 300-600 MU/min that is suitable for clinical treatment.
Lipodystrophy syndromes are extremely rare disorders of deficient body fat associated with potentially serious metabolic complications, including diabetes, hypertriglyceridemia, and steatohepatitis. Due to their rarity, most clinicians are not familiar with their diagnosis and management. This practice guideline summarizes the diagnosis and management of lipodystrophy syndromes not associated with HIV or injectable drugs.Seventeen participants were nominated by worldwide endocrine societies or selected by the committee as content experts. Funding was via an unrestricted educational grant from Astra Zeneca to the Pediatric Endocrine Society. Meetings were not open to the general public.A literature review was conducted by the committee. Recommendations of the committee were graded using the system of the American Heart Association. Expert opinion was used when published data were unavailable or scarce.The guideline was drafted by committee members and reviewed, revised, and approved by the entire committee during group meetings. Contributing societies reviewed the document and provided approval.Lipodystrophy syndromes are heterogeneous and are diagnosed by clinical phenotype, supplemented by genetic testing in certain forms. Patients with most lipodystrophy syndromes should be screened for diabetes, dyslipidemia, and liver, kidney, and heart disease annually. Diet is essential for the management of metabolic complications of lipodystrophy. Metreleptin therapy is effective for metabolic complications in hypoleptinemic patients with generalized lipodystrophy and selected patients with partial lipodystrophy. Other treatments not specific for lipodystrophy may be helpful as well (eg, metformin for diabetes, and statins or fibrates for hyperlipidemia). Oral estrogens are contraindicated.
Delayed puberty, while not uncommonly a variant of normal pubertal physiology, could be an indicator of a wide range of less common but important clinical disorders.Congenital pathologies may involve defective developments of the gonads, pituitary gonadotrophs or hypothalamic GnRH neurons.Acquired pathologies could likewise be acting at each level.Clinical diagnostic evaluation to delineate a good range of these disorders and the respective managements will be covered in this session.
BACKGROUND 5α-Reductase 2 deficiency (5ARD) is a known cause of 46,XY disorders of sex development (DSD). Traditionally, the diagnosis relies on dihydrotestosterone (DHT) measurement, but the results are often equivocal, potentially leading to misdiagnosis. We reviewed alternative approaches for diagnosis of 5ARD. METHODS We conducted a retrospective review of the results of urinary steroid profiling (USP) by GC-MS and mutational analysis of SRD5A2 [steroid-5-alpha-reductase, alpha polypeptide 2 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 2)] by PCR and direct DNA sequencing of all 46,XY DSD patients referred to our laboratory with biochemical and/or genetic findings compatible with 5ARD. We also performed a literature review on the laboratory findings of all 5ARD cases reported in the past 10 years. RESULTS Of 16 patients diagnosed with 5ARD between January 2003 and July 2012, 15 underwent USP, and all showed characteristically low 5α- to 5β-reduced steroid metabolite ratios. Four patients had DHT measured, but 2 did not reach the diagnostic cutoff. In all 12 patients who underwent genetic analysis, 2 mutations of the SRD5A2 gene were detected to confirm the diagnosis. Twenty-four publications involving 149 patients with 5ARD were published in the review period. Fewer than half of these patients had DHT tested. Nearly 95% of them had the diagnosis confirmed genetically. CONCLUSIONS 5ARD can be confidently diagnosed by USP at 3 months postnatally and confirmed by mutational analysis of SRD5A2. Interpretation of DHT results may be problematic and is not essential in the diagnosis of 5ARD. We propose new diagnostic algorithms for 46,XY DSD.
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