{beta}-thalassemia major evolution from {beta}-thalassemia minor is associated with paternal uniparental isodisomy of chromosome 11p15

beta-thalassemia major can be caused by homozygosity or compound heterozygosity for beta-globin gene mutations (HBB gene). Most cases are inherited from parents who both have diseased alleles of the HBB gene. We report a patient with late-onset beta-thalassemia major that evolved from beta-thalassemia minor in which only one of her parents had the diseased HBB gene. To study the cause of beta-thalassemia major in this patient, we performed the 100K single nucleotide polymorphism genotyping assay, fluorescence in situ hybridization, and DNA methylation analysis of the imprinting genes near the HBB gene. The results showed a loss of heterozygosity in the region of chromosome 11p14.3 to 11p15.5, which perfectly matched one allele of her father. Our study demonstrates that paternal uniparental isodisomy of chromosomal 11p15.5 is associated with the beta-thalassemia major in this patient. Key words: beta-thalassemia major, uniparental isodisomy, mosaicism.     

The increase of blood anticardiolipin antibody depends on the underlying etiology in cerebral ischemia.

Although anticardiolipin antibody (aCL) has been suggested to be a potent risk factor for thrombosis and atherosclerosis in multiple arterial beds, conflicting results still exist between aCL and cerebral ischemia in the general stroke population. To elucidate if this discrepancy relates to the heterogeneity of underlying etiologies, blood beta(2)-glycoprotein I dependent-aCL was evaluated in 432 Taiwanese adults associated with cerebral ischemia who were classified into five subtypes according to their causes of cerebral ischemia. The results were compared with those in 100 healthy controls. A definite increase of aCL-IgG isotype was found in 41 patients (9.35%) and four controls (4.0%). The relative risk was 2.52. The frequency of increased aCL-IgG was 12.2%, 12.8%, 8.8%, 3.9%, and 3.5% in patients with large-artery atherosclerotic disease, stroke of unknown etiology, small-artery occlusive disease, cardioembolism, and stroke of other known etiology, respectively. Only patient with large-artery atherosclerotic disease (p<0.025) and stroke of unknown etiology (p<0.05) had a higher frequency of increased aCL than control. The frequencies of abnormal result of activated partial thromboplastin time, antinuclear factor, Coombs' test, and venereal disease research laboratory were 2.84%, 1.22%, 1.02%, and 1.34% in these 41 patients, respectively. Accordingly, aCL-IgG selectively increases in patients with large-artery atherosclerosis and stroke of unknown etiology, reflecting selective activation of humoral immunity for aCL in the pathogenesis of cerebral ischemia.     

Interleukin-1 activates phospholipase A2 in human synovial cells

Interleukin-1 (IL-1) treatment of synovial cells from rheumatoid arthritis and osteoarthritis patients resulted in a dose-dependent secretion of phospholipase A2 (PLA2). IL-1 also stimulated prostaglandin E2 and plasminogen activator synthesis, in parallel with PLA2 activation; all 3 were detectable within 6 hours of IL-1 treatment and peaked by 24 hours. Synovial cell PLA2 required calcium (5 mM) and a neutral pH (7.5) for maximal activity and appears similar to the PLA2 in synovial fluid, which has been described previously. We conclude that PLA2 can be induced by IL-1, and its secretion may contribute significantly to the inflammatory actions of IL-1.     

Microbiology difference between colonized catheters and catheter-related bloodstream infections

BACKGROUND/AIMS: Central vein catheters for patients receiving total parenteral nutrition have a high incidence of colonized catheters and catheter-related bloodstream infections. However, the actual incidence and bacterial pattern have not been well studied. This study was undertaken to investigate the difference in bacteriology between colonized catheters and catheter-related bloodstream infections. METHODOLOGY: From January 1997 to March 1998, 354 patients receiving total parenteral nutrition were included in this study. The patients ranged in age from 49 to 80 years, 151 women and 203 men. Colonized catheters and catheter-related bloodstream infections were defined. RESULTS: The culture was performed in 249 catheter tips (249 of 614, 40.6%). Sixty tips were found to have organisms. The organisms cultured from colonized catheters were Gram(+) aerobic bacteria (34, 56.7%), fungi (14, 23.3%), and Gram(-) aerobic bacteria (12, 20%). The organisms cultured from catheter-related bloodstream infections were fungi (16, 64%), Gram(-) aerobic bacteria (5, 20%), and Gram(+) aerobic bacteria (4, 16%). Dermatogenic infection in colonized catheters should be stressed, but systemic fungal infection in catheter-related bloodstream infections should be emphasized. CONCLUSIONS: A striking difference exists in bacterial species between colonized catheters and catheter-related bloodstream infections. Further studies on different treatment strategy for colonized catheters and catheter-related bloodstream infections should be undertaken. The combined approach of a total parenteral nutrition team, sterile protocols, and early diagnosis of fungemia should be advocated for the total parenteral nutrition patients.     

The incidence of late-onset congenital adrenal hyperplasia due to 21-hydroxylase deficiency among hirsute women

Late-onset congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a cause of hirsutism in adult women. Its reported frequency of occurrence in hirsute women has varied from 0-30%, but the number of patients studied was small. To establish the incidence of CAH, 83 unselected hirsute women were studied prospectively with a standard ACTH stimulation test. On the basis of an exaggerated response of serum 17 alpha-hydroxyprogesterone to ACTH, 1 patient with CAH was found, for an incidence of 1.2%. The 95% confidence limits for the incidence of CAH among hirsute women were 0% and 3.4%. Five of seven hirsute women without CAH whose serum 17 alpha-hydroxyprogesterone levels rose above 3 ng/ml in response to ACTH had simultaneous serum progesterone values consistent with recent ovulation. Since routine screening of all hirsute women by means of ACTH stimulation does not appear to be cost effective, reported cases of CAH were reviewed in order to discern potentially helpful clinical clues. Severe hirsutism, virilization, early onset of symptoms, short stature, familial occurrence, and regular menses were identified as the clinical characteristics associated with late-onset CAH.     

The effect of percutaneous oestradiol on atheroma formation in ovariectomized cholesterol-fed rabbits

OBJECTIVE: The aim of this study was to examine the effect of percutaneous oestradiol on the lipid profile and on atheroma formation using an animal model. METHODS: The study was of 12 weeks duration. Fifty sexually mature female New Zealand White rabbits were divided into five groups of equal size. Two groups acted as controls and received normal rabbit chow. Rabbits in one of these groups were ovariectomized. The remaining three groups were ovariectomized but received 1% cholesterol enriched rabbit chow. One of these cholesterol-fed groups received 0.3 mg/kg percutaneous oestradiol daily whilst another received 0.1 mg/kg oral oestradiol daily. Measurements of concentrations of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were made at the beginning and end of the study. Aortic atheroma formation was measured using computerized image analysis of uptake of Sudan III staining. RESULTS: After 12 weeks there were significant increases in the mean concentrations of TC in the three cholesterol-fed groups compared with controls (P < 0.001). Changes in HDL-C and TG concentrations were less consistent. The mean area of aortic atheroma formation was significantly less in both the percutaneous oestradiol group (4.9%) and the oral oestradiol group (8.6%) compared with the non-oestrogen-treated cholesterol-fed group (19.5%) (P < 0.001, < 0.01 respectively). CONCLUSION: These results suggest that percutaneous oestradiol has a direct protective effect on atheroma formation independent of serum concentrations of total cholesterol.     

Intracardiac teratoma in a newborn

Primary tumors of the heart are infrequent at all ages. We present a newborn with hypoxia and a heart murmur, in whom an echocardiogram revealed a large tumor filling the right ventricle and the pulmonary annulus. To maintain pulmonary blood flow, the patency of the ductus arteriosus was achieved by infusion of prostaglandin E1. Successful surgical resection was accomplished. The pathological examination was characteristic of a benign teratoma. The patient remains asymptomatic and has shown no evidence of recurrence of the tumor during a follow-up period of 34 months. This represents the eleventh case of intracardiac teratoma and only the fourth case to undergo successful surgical resection.     

山楂饮片对胰脂肪酶活性的抑制作用研究

目的 探讨不同产地、不同品种的山楂样品对胰脂肪酶活性的抑制作用。方法 以对硝基苯基丁酸酯作为底物,在405 nm波长测定山楂饮片样品的水提物对胰脂肪酶体外活性。结果 各批次山楂样品对胰脂肪酶活性具有一定的抑制作用。结论 山楂可用于预防和治疗肥胖症;胰脂肪酶活性可作为山楂饮片等级划分的生物效应指标。