Advances in percutaneous valvular intervention

We are entering a new era in the percutaneous treatment of valvular heart disease. Novel techniques and devices have given rise to the possible treatment of a range of valvular heart diseases that previously necessitated surgical therapies, including aortic stenosis, pulmonary regurgitation and mitral regurgitation. Despite the enormous potential of these percutaneous therapies, enthusiasm needs to be balanced by an understanding of the challenges that need to be overcome before such therapies can be widely embraced. This review provides a critical assessment of the status of the major developments in percutaneous valvular intervention to date, and provides the authors' perspective on the current role and future potential of these techniques.     

An analysis of 45 years of reported overexposure incidents in Texas, 1956 to 2001

Sources of ionizing radiation are commonly encountered in a wide variety of modern work settings. The controls in place to ensure the safe use of these sources have proven to be quite effective, as events involving occupational doses in excess of established limits are quite rare. Nonetheless, instances of doses in excess of established limits, commonly referred to as "overexposures," do occur, but the rarity of such events has resulted in a body of scientific knowledge that consists essentially of sporadic case reports. In this study, incident reports describing radiation overexposure events recorded in Texas from the years 1956 to 2001 were obtained and recorded into a computerized database using a pre-established set of codes. The data were then analyzed for the identification of possible trends or commonalties. During the 45-y period of study, overexposure events accounted for 50% (n = 3,796) of all the radiation-related incidents recorded in Texas for the time period (n = 7,534). Of the overexposure events, 65% (n = 2,342) resulted in the actual deposition of energy in the individual exposed. The remainder were determined to be doses recorded only by a personal dosimetry device. In most of the cases where doses were actually delivered to an individual, the doses were less than 0.05 Sv (5 rem). In only 0.5% of the cases (n = 13) were doses greater than 1 Sv (100 rem). The predominant sources reported as involved in the events included 192Ir, 60Co, and 137Cs. The information derived from the analysis may serve as a basis for a variety of interventions, such as preventative education activities, regulatory modifications, and the possible re-design of equipment identified as commonly associated with such events. The results of the study can also assist in the training of health care providers, as the recognition of common causes and sources of overexposures and subsequent treatments can be forecasted and summary treatment protocols developed.     

Inhibition of 2-amino-3-methylimidazo[4,5-f]quinoline-DNA adducts by indole-3-carbinol: dose-response studies in the rat colon

Indole-3-carbinol (I3C) inhibits the formation of colonic aberrant crypt foci and DNA adducts in rats given heterocyclic amine colon carcinogens, such as 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Mechanism studies indicate that I3C induces cytochromes P4501A1 and 1A2 (CYP1A1 and CYP1A2), isozymes that respectively metabolize IQ via ring hydroxylation or activate the carcinogen by N-hydroxylation. The present study examined the dose-response for induction of CYP1A1 versus CYP1A2 by I3C, and compared the profiles of induction with the dose- response for inhibition of IQ-DNA adducts in the colon of the F344 rat. Dietary equivalent doses of I3C in the range 100-1000 p.p.m. increased in a dose-related manner both ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) activities in the liver and colonic mucosa, and Western blots showed a corresponding induction of CYP1A1 and CYP1A2 proteins. However, dietary equivalent doses of I3C in the range 10-25 p.p.m. (i) reduced hepatic EROD and MROD activities and CYP1A protein levels compared with controls, (ii) increased the ratio of CYP1A2 versus CYP1A1, and (iii) activated IQ to a more potent mutagen when liver microsomes from rats given I3C were used for metabolic activation in the Salmonella assay. Rats given a single oral dose of I3C shortly before administering IQ (5 mg/kg body wt, p.o.) exhibited dose-related inhibition of colonic IQ-DNA adducts in the range 25-100 p.p.m. I3C, reaching 95% inhibition at doses > or = 100 p.p.m. I3C, but IQ-DNA adducts were elevated slightly at the lowest I3C dose as compared with the controls. The possible significance of the low versus high dose effects of I3C are discussed in the context of human dietary exposures to I3C and the reported chemopreventive mechanisms of I3C in vivo.      

The genetic landscape of polycystic kidney disease in Ireland

Polycystic kidney diseases (PKDs) comprise the most common Mendelian forms of renal disease. It is characterised by the development of fluid-filled renal cysts, causing progressive loss of kidney function, culminating in the need for renal replacement therapy or kidney transplant. Ireland represents a valuable region for the genetic study of PKD, as family sizes are traditionally large and the population relatively homogenous. Studying a cohort of 169 patients, we describe the genetic landscape of PKD in Ireland for the first time, compare the clinical features of patients with and without a molecular diagnosis and correlate disease severity with autosomal dominant pathogenic variant type. Using a combination of molecular genetic tools, including targeted next-generation sequencing, we report diagnostic rates of 71–83% in Irish PKD patients, depending on which variant classification guidelines are used (ACMG or Mayo clinic respectively). We have catalogued a spectrum of Irish autosomal dominant PKD pathogenic variants including 36 novel variants. We illustrate how apparently unrelated individuals carrying the same autosomal dominant pathogenic variant are highly likely to have inherited that variant from a common ancestor. We highlight issues surrounding the implementation of the ACMG guidelines for variant pathogenicity interpretation in PKD, which have important implications for clinical genetics.Subject terms: Polycystic kidney disease, Disease genetics, Next-generation sequencing, Genetics research, Genetic testing     

Deletion/insertion mutation that causes biotinidase deficiency may result from the formation of a quasipalindromic structure

Biotinidase is responsible for recycling the vitamin biotin from biocytin that is formed after the proteolytic degradation of the biotin- dependent carboxylases. We have identified a deletion/insertion mutation within exon D of the human biotinidase gene in a child with biotinidase deficiency. The mutation causes a frame shift and premature termination which are predicted to result in a truncated protein. We propose that the mutation occurred during DNA replication by either of two mechanisms. Both mechanisms involve formation of a quasipalindromic hairpin loop in the template and dissociation of DNA polymerase alpha. This mutation supports the formation of palindromic structures as a possible cause of deletions in eukaryotes, and supports the proposal, derived from in vitro studies, that polymerase alpha may preferentially arrest or dissociate at specific template sequences.      

Paradoxical embolization of a fractured guidewire: successful retrieval from left atrium using a snare device.

In adults, paradoxical embolization of catheters or guidewire fragments related to central venous catheterization is a rare phenomenon. Reports of successful percutaneous retrieval of foreign bodies from the left atrium is also rare. We describe the successful percutaneous retrieval of a fractured guidewire that had undergone paradoxical embolization to the left atrium in an adult patient.     

去氢表雄酮硫酸酯钠盐对妊娠大鼠子宫颈张力的影响及作用机理

去氢表雄酮硫酸酯为正常人体肾上腺所分泌,是合成雄激素和雌激素的前体。1970年日本钟仿制药厂正式生产该产品作为宫颈成熟剂,用于治疗宫颈成熟不全和产程延长等。Mochizuki给妊娠末期的妇女ⅳ去氢表雄酮硫酸酯钠盐(OHA-S)100 mg,共2次,发现DHA-S能促进子     

二苯乙烯类化合物对蛋白激酶C的抑制作用

报道15种二苯乙烯类化合物对蛋白激酶C(PKC)活性的影响。其中从中药金雀根中分得的3种二苯乙烯类低聚体α-viniferin,kobophenol A 和 miyabenolC,它们抑制PKC的IC₅₀分别为62.5,52.0和27.5μmol·L^-1。另外6种含酚羟基的二苯乙烯化合物对PKC也显示不同程度的抑制作用,但当酚羟基全甲基化或全乙酰化后其抑制作用大大降低甚至消失。酶动力学研究证明miyabenolC对PKC的抑制作用属于非竞争性抑制。