Large-body radiation doses following radioiodine therapy

In accordance with the recommendations of the International Radiological Protection Commission, the current maximum acceptable radiation dose limits for members of the public have been reduced to 1 mSv in the United States, Canada, and European Union countries including the United Kingdom. This has had a significant impact on radiation protection guidelines for contacts of patients treated with 131I. Many previous recommendations have relied upon models which may overestimate dose rates at short distances. We therefore undertook measurements of 131I dose rates using adult and infant phantoms that more accurately reflected true geometry. Effective dose calculations and patient contact restrictions were then derived from these direct dose measurements. Doses received by the adult phantom were measured at three distances (contact, 1.0 m, 2.0 m) and doses received by the infant phantom were measured at contact in two orientations (adult cradling infant over shoulder and at waist). The doses measured were significantly lower than previously predicted for the adult and infant phantom. Our measurements suggest that patient contact restrictions could be made less stringent than those currently in widespread use.     

Comparison of two superparamagnetic viral-sized iron oxide particles ferumoxides and ferumoxtran-10 with a gadolinium chelate in imaging intracranial tumors

BACKGROUND AND PURPOSE: Ultrasmall superparamagnetic iron oxide particles result in shortening of T1 and T2 relaxation time constants and can be used as MR contrast agents. We tested four hypotheses by evaluating MR images of intracranial tumors after infusion of two iron oxide agents in comparison with a gadolinium chelate: 1) Ferumoxtran in contrast to ferumoxides can be used as an intravenous MR contrast agent in intracranial tumors; 2) ferumoxtran enhancement, albeit delayed, is similar to gadolinium enhancement; 3) ferumoxtran-enhanced MR images in contrast to gadolinium-enhanced MR images may be compared with histologic specimens showing the cellular location of iron oxide particles; 4) ferumoxtran can serve as a model for viral vector delivery. METHODS: In 20 patients, ferumoxides and ferumoxtran were intravenously administered at recommended clinical doses. MR imaging was performed 30 minutes and 4 hours after ferumoxides infusion (n = 3), whereas ferumoxtran-enhanced MR imaging (n = 17) was performed 6 and 24 hours after infusion in the first five patients and 24 hours after infusion in the remaining 12. MR sequences were spin-echo (SE) T1-weighted, fast SE T2- and proton density-weighted, gradient-recalled-echo T2*-weighted, and, in four cases, echo-planar T2-weighted sequences. Representative regions of interest were chosen on pre- and postcontrast images to compare each sequence and signal intensity. RESULTS: Despite some degree of gadolinium enhancement in all tumors, no significant T1 or T2 signal intensity changes were seen after ferumoxides administration at either examination time. Fifteen of 17 patients given ferumoxtrans had T1 and/or T2 shortening consistent with iron penetration into tumor. Histologic examination revealed minimal iron staining of the tumor with strong staining at the periphery of the tumors. CONCLUSION: 1) Ferumoxtran can be used as an intravenous MR contrast agent in intracranial tumors, mostly malignant tumors. 2) Enhancement with ferumoxtran is comparable to but more variable than that with the gadolinium chelate. 3) Histologic examination showed a distribution of ferumoxtran particles similar to that on MR images, but at histology the cellular uptake was primarily by parenchymal cells at the tumor margin. 4) Ferumoxtran may be used as a model for viral vector delivery in malignant brain tumors.     

Identifying patients at risk for intracranial and extracranial blunt carotid injuries

BACKGROUND: Blunt carotid injuries are rare, often occult, and potentially devastating. Angiographic screening programs have detected this injury in up to 1% of blunt trauma patients. Implementing a liberal angiographic screening program at our hospital is impractical and we want to identify a high-risk group to target for screening. We hypothesize that intracranial and extracranial carotid injuries have different risks, presentations, and outcomes. METHODS: Patients with intracranial and extracranial carotid injuries were identified from the British Columbia trauma registry. Presentation and outcome were reviewed. To facilitate statistical modeling the analysis was done by matching cases to 5 randomly selected controls. Risk factors for injury were evaluated by univariate and multiple logistic regression. RESULTS: A total of 35 carotid injuries were identified. Thirteen intracranial injuries were identified in 10 patients. Twenty-two extracranial injuries were identified in 18 patients. Sixty-seven percent of patients with intracranial injuries and 31% of those with extracranial injuries died (P = 0.11). Eleven percent of intracranial injuries and 56% of extracranial injuries were occult (P = 0.04). Glasgow outcome scores were 2.04 intracranial and 3.12 extracranial (P = 0.18). For intracranial injuries the multiple variable predictive model had two predictors: Glasgow Coma Score or =3). CONCLUSIONS: Intracranial injuries were frequently detected on initial investigations and have very poor outcomes. Extracranial injuries were more frequently occult and stand to benefit from early detection by screening programs. As independent risk factors for these two injuries differ, limited screening resources should focus on risk factors for occult extracranial injury: namely, low GCS and significant thoracic injury.     

Renal abnormalities in beckwith-wiedemann syndrome are associated with 11p15.5 uniparental disomy

Beckwith-Wiedemann syndrome (BWS) is a somatic overgrowth syndrome characterized by a variable incidence of congenital anomalies, including hemihyperplasia and renal malformations. BWS is associated with disruption of genomic imprinting and/or mutations in one or more genes encoded on 11p15.5, including CDKN1C (p57(KIP2)). It was hypothesized that genotypic and epigenotypic abnormalities of the 11p15.5 region affecting CDKN1C were associated with renal abnormalities. Medical records for 159 individuals with BWS were reviewed. All underwent at least one abdominal ultrasonographic evaluation. Testing for paternal uniparental disomy (UPD) at 11p15.5, CDKN1C mutations, and imprinting defects at KvDMR1 was performed for 96, 32, and 47 patients, respectively. Of the 159 patients, 67 (42%) exhibited renal abnormalities, mainly nephromegaly (25%), collecting system abnormalities (11%), and renal cysts (10.5%). The frequency of renal lesions among patients who were tested for genetic abnormalities did not differ from that among patients who were not tested. Paternal UPD was demonstrated in 22 of 96 cases (23%), CDKN1C mutations in eight of 32 cases (25%), and KvDMR1 imprinting defects in 21 of 47 cases (45%). The 22 UPD-positive patients exhibited a significantly higher incidence of renal abnormalities (P = 0.0026). Surprisingly, the eight patients with CDKN1C mutations exhibited no significant increase in the incidence of renal lesions (P = 0.29). Imprinting defects at KvDMR1, which might downregulate CDKN1C, were also not associated with a significant difference in the incidence of renal disease. Whereas UPD at 11p15.5 in BWS was associated with a higher incidence of renal abnormalities, mutations at CDKN1C and KvDMR1 imprinting defects were not, suggesting that imprinted genes on 11p15.5 other than CDKN1C are critical for renal development.     

Pedicled vascularized bone grafts for disorders of the carpus: scaphoid nonunion and Kienbock's disease

The use of reverse-flow pedicled vascularized bone grafts from the dorsal distal radius makes it possible to transfer bone with a preserved circulation and viable osteoclasts and osteoblasts. The resultant primary bone healing without creeping substitution within the dead bone is an alternative to conventional bone grafting in aiding or accelerating healing, replacing deficient bone, and/or revascularizing ischemic bone. Recent advances in understanding the anatomy and physiology of vascularized pedicled bone grafts have increased their use in treating a variety of carpal maladies. A basic understanding of the vascular anatomy, as well as the surgical principles and experimental and clinical results of pedicled vascularized bone grafts from the dorsal distal radius, is critical to understanding the use of these grafts in the treatment of scaphoid nonunions and Kienbock's disease.     

Serotonin 2A -1438 G/A and G-protein Beta3 subunit C825T polymorphisms in patients with depression and SSRI-associated sexual side-effects.

The occurrence of sexual side-effects from antidepressants is thought to be mediated through serotonin 2A (5HT2A) receptors. It is currently unknown if functional polymorphisms in the 5HT2A receptor or its G-protein second messenger complex are related to sexual dysfunction in patients taking an selective serotonin reuptake inhibitor (SSRI) for depression. The purpose of this study was to determine the relationship of the 5HT2A -1438 G/A and GNB3 C825T single nucleotide polymorphisms with overall sexual well-being and individual components of sexual health as measured by the Changes in Sexual Functioning Questionnaire (CSFQ). We evaluated 89 outpatients (18-40 years of age) at low risk for other causes of sexual dysfunction who were being treated for depression with an SSRI and did not have sexual difficulties before taking the antidepressant. Outcome measures were stratified by 5HT2A and GNB3 genotypes. After controlling for age, gender, anxiety scale scores, and depression scale scores, persons with a GG genotype of the 5HT2A -1438 single nucleotide polymorphisms (SNP) were significantly more likely to be categorized as having sexual dysfunction than persons with a GA or AA genotype (OR=3.6; 95% CI 1.03, 12.6; p=0.046). Furthermore, the 5HT2A -1438 GG genotype was a significant predictor of lower arousal scores (p=0.022) after accounting for other measures. There was no significant relationship between any outcome measure and GNB3 genotype.     

In vitro and in vivo correlation of hepatic transporter effects on erythromycin metabolism: characterizing the importance of transporter-enzyme interplay.

The effects of hepatic uptake and efflux transporters on erythromycin (ERY) disposition and metabolism were examined by comparing results from rat hepatic microsomes, freshly isolated hepatocytes, and in vivo studies. Uptake studies carried out in freshly isolated rat hepatocytes showed that ERY and its metabolite (N-demethyl-ERY) are substrates of Oatp1a4 and Oatp1b2. Whereas rifampin and GG918 [GF120918: N-{4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)-ethyl]-phenyl}-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamine] exerted minimal effects on metabolism in microsomes, rifampin (2.5 microM) and GG918 (0.5 microM) significantly decreased and increased ERY metabolism in hepatocytes, respectively. Concentration-time course studies further demonstrated that, compared with the intracellular N-demethyl-ERY control area under the curve (AUC) (0.795 +/- 0.057 microM . min), a decreased AUC (0.513 +/- 0.028 microM . min, p < 0.005) was observed when ERY was coincubated with rifampin, and an increased AUC (2.14 +/- 0.21 microM . min, p < 0.05) was found when GG918 was present. The results of the i.v. bolus studies showed that, compared with the ERY clearance of the controls (47.2 +/- 12.5 ml/min/kg for the rifampin group and 42.1 +/- 5.7 for the GG918 group), a decreased blood clearance, 29.8 +/- 6.1 ml/min/kg (p < 0.05) and 21.7 +/- 9.0 ml/min/kg (p < 0.01), was observed when rifampin or GG918, respectively, was coadministered. When either inhibitor was codosed with ERY, volume of distribution at steady state was unchanged, but t1/2 and mean residence time significantly increased compared with the controls. Hepatic uptake and efflux transporters modulate intracellular concentrations of ERY, thereby affecting metabolism. The interplay of transporters and enzymes must be considered in evaluating potential drug-drug interactions.     

Unidentified under-nutrition: dietary intake and anthropometric indices in a residential care home population

BACKGROUND: Research investigating the nutritional status of older people in residential care homes is scant. OBJECTIVE: To determine the anthropometric measures and dietary intakes of older people in this setting as a basis for future intervention studies. METHODS: Dietary intake was assessed using 3-day-weighed food records, nutritional status was evaluated using anthropometric measurements (knee height to predict standing height, and body weight). Catering provision was assessed using a computer-based menu assessment tool (CORA). RESULTS: Mean body mass index (BMI) for the 34 participants was 22.2 kg m(2) (range 14.5-34.4). Six participants (17.6%) had a BMI < or =18.5 kg m(2) with a further seven identified as having a BMI >18.5 but <20 kg m(2). Only two subjects with BMI <18.5 kg m(2) were prescribed oral supplements. In both men and women, recorded mean energy intakes were below current estimated average requirements by 24% and 22% respectively. CONCLUSION: Despite adequate food provision, under-nutrition was prevalent and, in the majority of cases, unidentified and untreated. A larger study is warranted to investigate whether improved nutritional intake is achievable through dietary modification. These data indicate that a sample size of around 60, with 90% power and at the 5% significance level, is required to detect a difference of 1674 kJ between groups of residents in an intervention study following a cluster randomized design.