Effect of scattering and differential attenuation on beam profile in the presence of high-density intensity modifying compensator.

AIM: The aim of this study is to investigate the effect of scattering and differential attenuation on dose profile of 6 MV photon beam in the presence of cadmium (Cd)-free compensator which has been used in compensator-based intensity-modulated radiotherapy. MATERIALS AND METHODS: Totally, 10 slabs of Cd-free compensator having thicknesses ranging from 2.4 to 61.4 mm have been prepared. Dose profiles have been taken using computer-controlled radiation field analyzer for five field sizes from 30 mm × 30 mm to 200 mm × 200 mm and at three depths in water phantom. Off-axis dose variation (ODV) has been measured with off-axis percentage depth dose scan and with ion chamber by measuring point dose at two diagonal points with respect to dose at central axis point in a plane and at three depths. RESULTS: A decrease in beam flatness has been observed with increase in compensator thickness and depth in phantom. ODV has been found to increase with compensator thickness. Selective beam hardening has been observed due to differential attenuation from compensator. Point dose measurements show approximately 20% and 23% underdose region at 70 and 106 mm off-axis diagonal point, respectively, as compared to dose at central axis point for a field size of 200 mm × 200 mm at a depth of 15 mm, with 30.2-mm slab thickness. Significant increase in scattered penumbra has been observed with field size and thickness of compensator due to increase in scattered photon. CONCLUSIONS: The presence of compensator changes photon beam mean energy along the cross-section resulted in decreased beam flatness and increased scattering. This may lead to overestimation of dose along off-axis within radiation field if change in flatness is not taken into account and more exposure to healthy tissues in penumbral region due to large-angle scattering.

The effect of sodium and angiotensin-converting enzyme inhibition on the classic circulating renin-angiotensin system in autosomal-dominant polycystic kidney disease patients.

BACKGROUND: It has been suggested that inappropriate stimulation of the renin-angiotensin system (RAS) is responsible for the increase in blood pressure that occurs in autosomal-dominant polycystic kidney disease (ADPKD) before the development of renal failure. However, the interpretation of previous studies in ADPKD patients is confounded by inadequate matching with control populations for blood pressure and renal function, or failure to control the sodium intake of participants. METHODS: A double-blind, placebo-controlled study of two different sodium intakes (350 and 50 mmol/day for 5 days) in a group of 11 hypertensive ADPKD patients and eight matched control subjects with essential hypertension. In addition, blood pressure and hormonal responses were measured after the administration of the angiotensin-converting enzyme inhibitor enalapril for 3 days. RESULTS: Blood pressure and hormonal responses of the RAS after a reduction in sodium intake and after the administration of enalapril were identical in ADPKD patients and controls. CONCLUSIONS: Activation of the classic circulating RAS is no greater in hypertensive ADPKD patients than in individuals with essential hypertension.

Association of mutation position in polycystic kidney disease 1 (PKD1) gene and development of a vascular phenotype.

BACKGROUND: Patients with autosomal dominant polycystic kidney disease (ADPKD) are at risk of developing intracranial aneurysms, and subarachnoid haemorrhage is a major cause of death and disability. Familial clustering of intracranial aneurysms suggests that genetic factors are important in the aetiology. We tested whether the germline mutation predisposes to this vascular phenotype. METHODS: DNA samples from patients with ADPKD and vascular complications were screened for mutations throughout the PKD1 and PKD2 genes. Comparisons were made between the PKD1 and PKD2 populations and with a control PKD1 cohort (without the vascular phenotype). FINDINGS: Mutations were characterised in 58 ADPKD families with vascular complications; 51 were PKD1 (88%) and seven PKD2 (12%). The median position of the PKD1 mutation was significantly further 59 in the vascular population than in the 87 control pedigrees (aminoacid position 2163 vs 2773, p=0.0034). Subsets of the vascular population with aneurysmal rupture, early rupture, or families with more than one vascular case had median mutation locations further 59 (aminoacid position 1811, p=0.0018; 1671, p=0.0052; and 1587, p=0.0003). INTERPRETATION: Patients with PKD2, as well as those with PKD1, are at risk of intracranial aneurysm. The position of the mutation in PKD1 is predictive for development of intracranial aneurysms (59 mutations are more commonly associated with vascular disease) and is therefore of prognostic importance. Since the PKD1 phenotype is associated with mutation position, the disease is not simply due to loss of all disease allele products.

A complete mutation screen of the ADPKD genes by DHPLC.

BACKGROUND: Genetic analysis is a useful diagnostic tool in autosomal dominant polycystic kidney disease (ADPKD), especially when imaging results are equivocal. However, molecular diagnostics by direct mutation screening has proved difficult in this disorder due to genetic and allelic heterogeneity and complexity of the major locus, PKD1. METHODS: A protocol was developed to specifically amplify the exons of PKD1 and PKD2 from genomic DNA as 150 to 450 bp amplicons. These fragments were analyzed by the technique of denaturing high-performance liquid chromatography (DHPLC) using a Wave Fragment Analysis System (Transgenomics) to detect base-pair changes throughout both genes. DHPLC-detected changes were characterized by sequencing. RESULTS: Cost effective and sensitive mutation screening of the entire coding regions of PKD1 and PKD2 by DHPLC was optimized. All base-pair mutations to these genes that we previously characterized were detected as an altered DHPLC profile. To assess this method for routine diagnostic use, samples from a cohort of 45 genetically uncharacterized ADPKD patients were analyzed. Twenty-nine definite mutations were detected, 26 PKD1, 3 PKD2 and a further five possible missense mutations were characterized leading to a maximal detection rate of 76%. A high level of polymorphism of PKD1 also was detected, with 71 different changes defined. The reproducibility of the DHPLC profile enabled the recognition of many common polymorphisms without the necessity for re-sequencing. CONCLUSIONS: DHPLC has been demonstrated to be an efficient and effective means for gene-based molecular diagnosis of ADPKD. Differentiating missense mutations and polymorphisms remains a challenge, but family-based segregation analysis is helpful.