Renal thorium deposition associated with transitional cell carcinoma: radiologic demonstration in two patients

Abdominal radiography, excretory urography, retrograde pyelography, and computed tomography were performed in two patients who had undergone retrograde pyelography with thorium dioxide (Thorotrast) approximately 40 years ago. Both patients developed a transitional cell carcinoma due to suburothelial thorium deposition. Typical thorium densities were demonstrated at CT in the peripelvicalyceal area as well as in retroperitoneal lymph nodes. Elderly patients in whom radiographic examination reveals retained Thorotrast in the kidney should be followed up because of the high risk of renal carcinoma.     

Klatskin tumors of the bile ducts: sonographic appearance

The authors present 3 cases of surgically proved Klatskin tumor diagnosed by ultrasound alone. Sonographic features of these tumors include (a) dilatation of the intrahepatic biliary ducts but not the extrahepatic duct, (b) non-union of the right and left hepatic ducts, and (c) small, solid masses at the hepatic hilus. Local spread to the liver may also be seen. If the pancreas appears normal and no primary tumor can be found, Klatskin tumor can be diagnosed with a high degree of accuracy.     

Assessment of the steady-state pharmacokinetic interaction between etravirine administered as two different formulations and tenofovir disoproxil fumarate in healthy volunteers

Objective

Two open‐label, randomized, cross‐over trials in healthy volunteers were conducted to investigate the pharmacokinetic interaction between etravirine and tenofovir disoproxil fumarate.

Methods

Etravirine was administered as either 800 mg twice a day (bid) (phase II formulation in Study 1) or 200 mg bid (phase III formulation in Study 2) for 8 days followed by a 12 h pharmacokinetic evaluation. After a minimum of 14 days washout, tenofovir disoproxil fumarate 300 mg once a day was administered for 16 days. Volunteers were randomized to receive co‐administration of etravirine with tenofovir disoproxil fumarate on either days 1–8 or days 9–16 followed by a 12 h pharmacokinetic evaluation for etravirine on day 8 or 16, respectively. Plasma and urine tenofovir concentrations were determined on days 8 and 16 over 24 h.

Results

The least square mean (LSM) ratio [90% confidence interval (CI)] for the area under the plasma concentration–time curve from 0 to 12 h (AUC_{12 h}) for etravirine co‐administered with tenofovir disoproxil fumarate vs. etravirine alone was 0.69 (0.61–0.79) and 0.81 (0.75–0.88) in Studies 1 and 2, respectively. The LSM ratio (90% CI) for the effect of etravirine on tenofovir AUC_{24 h} was 1.16 (1.09–1.23) in Study 1 and 1.15 (1.09–1.21) in Study 2.

Conclusions

These alterations are not considered clinically relevant for either drug and no dose adjustment is necessary when etravirine and tenofovir disoproxil fumarate are co‐administered.     

Phenotype determining alleles in GM1 gangliosidosis patients bearing novel GLB1 mutations

Hofer D, Paul K, Fantur K, Beck M, Roubergue A, Vellodi A, Poorthuis BJ, Michelakakis H, Plecko B, Paschke E. Phenotype determining alleles in GM1 gangliosidosis patients bearing novel GLB1 mutations. GM1 gangliosidosis manifests with progressive psychomotor deterioration and dysostosis of infantile, juvenile, or adult onset, caused by alterations in the structural gene coding for lysosomal acid ß‐galactosidase (GLB1). In addition, allelic variants of this gene can result in Morquio B disease (MBD), a phenotype with dysostosis multiplex and entire lack of neurologic involvement. More than 100 sequence alterations in the GLB1 gene have been identified so far, but only few could be proven to be predictive for one of the GM1 gangliosidosis subtypes or MBD. We performed genotype analyses in 16 GM1 gangliosidosis patients of all phenotypes and detected 28 different genetic lesions. Among these, p.I55FfsX16, p.W65X, p.F107L, p.H112P, p.C127Y, p.W161X, p.I181K, p.C230R, p.W273X, p.R299VfsX5, p.A301V, p.F357L, p.K359KfsX23, p.L389P, p.D448V, p.D448GfsX8, and the intronic mutation IVS6‐8A>G have not been published so far. Due to their occurrence in homozygous patients, four mutations could be correlated to a distinct GM1 gangliosidosis phenotype. Furthermore, the missense mutations from heteroallelic patients and three artificial nonsense mutations were characterized by overexpression in COS‐1 cells, and the subcellular localization of the mutant proteins in fibroblasts was assessed. The phenotype specificity of 10 alleles can be proposed on the basis of our results and previous data.