SMAD4 gene mutation increases the risk of aortic dilation in patients with hereditary haemorrhagic telangiectasia.

BACKGROUND: Mutations in the genes ENG, ACVRL1 and SMAD4 that are part of the transforming growth factor-beta signalling pathway cause hereditary haemorrhagic telangiectasia (HHT). Mutations in non-HHT genes within this same pathway have been found to associate with aortic dilation. Therefore, we investigated the presence of aortic dilation in a large cohort of HHT patients as compared to non-HHT controls. METHODS: Chest computed tomography of consecutive HHT patients (ENG, ACVRL1 and SMAD4 mutation carriers) and non-HHT controls were reviewed. Aortic root dilation was defined as a z-score>1.96. Ascending and descending aorta dimensions were corrected for age, gender and body surface area. RESULTS: In total 178 subjects (57.3% female, mean age 43.9±14.9years) were included (32 SMAD4, 47 ENG, 50 ACVRL1 mutation carriers and 49 non-HHT controls). Aortopathy was present in a total of 42 subjects (24% of total). Aortic root dilatation was found in 31% of SMAD4, 2% of ENG, 6% of ACVRL1 mutation carriers, and 4% in non-HHT controls (p<0.001). The aortic root diameter was 36.3±5.2mm in SMAD4 versus 32.7±3.9mm in the non-SMAD4 group (p=0.001). SMAD4 was an independent predictor for increased aortic root (ß-coefficient 3.5, p<0.001) and ascending aorta diameter (ß-coefficient 1.6, p=0.04). CONCLUSIONS: SMAD4 gene mutation in HHT patients is independently associated with a higher risk of aortic root and ascending aortic dilation as compared to other HHT patients and non-HHT controls.

Role of Magnetic Resonance Elastography as a Noninvasive Measurement Tool of Fibrosis in a Renal Allograft: A Case Report.

A major reason for poor long-term kidney transplant outcomes is the development of chronic allograft injury, characterized by interstitial fibrosis and tubular atrophy. Currently, an invasive biopsy that samples only <1% of the kidney is the gold standard for detecting kidney allograft fibrosis. We report the use of magnetic resonance elastography (MRE) to quantify tissue stiffness as a noninvasive and whole-kidney measurement tool of allograft fibrosis in a kidney transplant patient at 2 time points. The MRE whole-kidney stiffness values reflected the changes in fibrosis of the kidney allograft as assessed by histologic examination. To our knowledge, this technique is the first observation of change over time in MRE-derived whole-kidney stiffness in an allograft that is consistent with changes in histology-derived fibrosis scores in a single patient.

Dissociation dynamics of transient anion formed via electron attachment to sulfur dioxide.

We report the molecular dynamics of dissociative electron attachment to sulfur dioxide (SO2) by measuring the momentum distribution of fragment anions using the velocity slice imaging technique in the electron energy range of 2-10 eV. The S- channel results from symmetric dissociation which exhibits competition between the stretch mode and bending mode of vibration in the excited parent anion. The asymmetric dissociation of parent anions leads to the production of O- and SO- channels where the corresponding neutral fragments are formed in their ground as well as excited electronic states. We also identify that internal excitation of SO- is responsible for its low yield at higher electron energies.

A time of flight mass spectrometer with field free interaction region for low energy charged particle-molecule collision studies.

A new design of a linear time of flight mass spectrometer (ToFMS) is implemented that gives nearly field-free interaction region without compromising on the mass resolution. The design addresses problems that would arise in a conventional Wiley-McLaren type of ToFMS: (i) field leakages into the charged particle-molecule interaction region from various components of the mass spectrometer, including that through the high transparency mesh used to obtain evenly distributed electric fields; (ii) complete collection and transportation of the ions produced in the interaction region to the detector, which is essential for high sensitivity and cross section measurements. This ToFMS works over a wide range of masses from H(+) to a few hundred Daltons and would be the most suitable for low energy charged particle-molecule interaction studies. Performance of the ToFMS has been tested by measuring the partial ionization cross sections for electron impact on CF(4).

A case of right-sided congenital subclavian steal.

A 21-year-old man presented with an uncommon asymptomatic case of right-sided congenital subclavian steal. On physical examination, his blood pressure was 115/80 mmHg in the left arm, but could not be measured in the right arm. Magnetic resonance angiography demonstrated that the origin of the right subclavian artery was atretic, and supplied by a number of collaterals near the origins of the internal mammary and vertebral arteries. Subclavian steal should be a diagnostic consideration in any patient who presents with a pulse deficit or a systolic blood pressure difference of greater than 15 mmHg. A description of the acquired and congenital varieties of subclavian steal is provided.

Risk factors for the development of cephalic arch stenosis.

PURPOSE: The creation of a vascular access is necessary in hemodialysis patients, including those with marginal vessels. Upper arm fistulae are attractive due to the ease of creation and of achieving high access flow rates. Cephalic arch stenosis (CAS) can lead to failure of upper arm fistulae and is increasingly identified. We hypothesized that CAS is promoted by high blood flow rates, brachiocephalic fistulae, and an angle of cephalic vein insertion approaching 90 degrees. METHODS: All patients requiring a fistulogram between January 2004 and May 2006 had surveillance fluoroscopy of the central veins. Demographic, clinical and laboratory parameters were collected and the angle of the cephalic vein insertion measured by 3 blinded independent observers. RESULTS: Fifty-eight patients had fistulograms and CAS was detected in 18 subjects. Significant differences between the CAS and non-CAS groups were brachiocephalic fistula site (p = 0.046), access flow (mL/min) (p = 0.012), and absence of diabetes (p = 0.03). Univariate predictors of CAS include access flow (per 100 mL/min) (p = 0.042), platelet count (p = 0.031) and calcium-phosphate product (p = 0.026). The relationship of brachiocephalic site and CAS was confounded by access flow [(per 100 mL/min)*brachiocephalic fistula site (p = 0.016)] and fistula age [brachiocephalic fistula site*fistula age (p = 0.017)]. In multivariate analysis, renovascular disease, calcium-phosphate product, platelet count and access flow (per 100 mL/min)*brachiocephalic fistula predicted CAS (p < 0.001, Negelkerke's R-Square = 0.55). The angle of insertion of the cephalic vein was not predictive for CAS. CONCLUSIONS: CAS may be a long-term consequence of high blood flow rates. The interaction of access flow and brachiocephalic fistula supports the hypothesis that high flow through a brachiocephalic fistula promotes CAS. The multiple factors influencing cephalic arch remodeling require further research.

Stent graft in managing juxta-renal aortoiliac occlusion.

Endovascular procedures are frequently used as an alternative to surgical bypass in aortic and iliac occlusion. Stents have revolutionized the scope of such endovascular procedures, but there are few reports of stents or stent grafts in occlusive juxta-renal aortic occlusion. We present a case where such occlusion was managed by use of a stent graft with successful outcome.

A continuous culture system of direct somatic embryogenesis in microspore-derived embryos of Brassica juncea.

An efficient culture system has been developed for repeated cycles of somatic embryogenesis in microspore-derived embryos of Brassica juncea without a callus phase. Haploid embryos produced through anther culture showed a high propensity for direct production of somatic embryos in response to 2 mgL(-1) BA and 0.1 mgL(-1) NAA. The embryogenic cultures which comprised the elongated embryonal axis of microspore-derived embryos when explanted and grown on the medium of same composition produced a large number of secondary embryos. These somatic embryos in turn underwent axis elongation and produced more somatic embryos when explanted and cultured. This cycle of repetitive somatic embryogenesis continued with undiminished vigour passage after passage and was monitored for more than a year. Somatic embryos from any passage when isolated at cotyledonary stage and grown on auxin-free medium for 5 days and then on a medium containing NAA (0.1 mgL(-1)), developed into complete plants with a profuse root system and were easily established in the soil. The cytology of the root tips of these plants confirmed their haploid nature. The total absence of callus phase makes the system ideal for continuous cloning of androgenic lines, Agrobacterium-mediated transformation and mutation induction studies.