Epiphyseal involvement of simple bone cysts

Epiphyseal involvement of a simple bone cyst (SBC) is uncommon. Eight patients are reported in whom an SBC was found to cross the growth plate, involving the epiphysis in seven patients and the apophysis in one. All patients had more than two pathologic fractures. In seven patients growth disturbance was found. Functional impairment did not develop in any patient. Radiographically, all lesions presented a characteristic involvement of the epiphysis and metaphysis in various proportions. Only one of four cysts treated with methylprednisolone acetate injections showed incomplete healing; the others failed to respond. After percutaneous grafting of autologous bone marrow, three of seven cysts healed and the others attained incomplete healing. Epiphyseal involvement of SBC should be considered a more aggressive form of an active lesion.     

Nano- and microparticles as adjuvants in vaccine design: success and failure is related to host natural antibodies

Bovine serum albumin (BSA) and the surface A-layer protein (AP) of an atypical strain of fish bacterial pathogen Aeromonas salmonicida were covalently linked with polymeric nano- and microparticles, and antigenicity of the resulted conjugates was compared in mice and goldfish. Distinct albeit different levels of natural BSA and AP antibodies were present in both animal species. Significant stimulation of the anti-AP antibody response in mice strikingly contrasted to unresponsiveness or even suppression in fish. The results negatively correlate with the levels of respective natural antibodies in the host and are discussed in context of problems related to fish vaccination. The work reinforces the instructive role of natural antibodies in adaptive immune response.     

Sunitinib in patients with metastatic renal cell carcinoma

Context  Current treatment options for metastatic renal cell carcinoma (RCC) are limited and there is a need to identify novel and effective therapies. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, which has shown activity in an initial study of cytokine-refractory metastatic RCC patients. Objective  To confirm the antitumor efficacy of sunitinib as second-line treatment in patients with metastatic clear-cell RCC, the predominant cell type of this malignancy. Design, Setting, and Patients  Open-label, single-arm, multicenter clinical trial. Patients were enrolled between February and November 2004, with follow-up continuing until disease progression, unacceptable toxicity, or withdrawal of consent. The reported data apply through August 2005. Patients (N = 106) had metastatic clear-cell RCC, which had progressed despite previous cytokine therapy. Intervention  Repeated 6-week cycles of sunitinib, 50 mg per day given orally for 4 consecutive weeks followed by 2 weeks off per treatment cycle. Main Outcome Measures  Assessment of clinical response, degree of tumor regression on imaging studies using the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Primary end point was overall objective response rate (complete plus partial). Secondary end points were progression-free survival and safety. Response was evaluated by independent third-party core imaging laboratory and by treating physicians (investigator assessment). Results  All 106 patients received sunitinib and were included in the intent-to-treat population for safety analyses. Of these, 105 patients were evaluable for efficacy analyses. The objective response rate according to an independent third-party assessment resulted in 36 patients with partial response (34%; 95% confidence interval, 25%-44%), and a median progression-free survival of 8.3 months (95% confidence interval, 7.8-14.5 months). The most common adverse events experienced by patients were fatigue in 30 (28%) and diarrhea 21 (20%). Neutropenia, elevation of lipase, and anemia were the most common laboratory abnormalities observed in 45 (42%), 30 (28%), and 27 (26%) patients, respectively. Conclusion  The results of this trial demonstrate the efficacy and manageable adverse-event profile of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC. Trial Registration  clinicaltrials.gov Identifier: NCT00077974      

Benzene in blood and phenol in urine in monitoring benzene exposure in industry

Determinations of benzene concentration in blood and of phenol in urine were made by head-space gas chromatography techniques on samples taken near the end of the work day from two groups of workers potentially exposed to low levels of benzene in the work-place atmosphere. Preliminary results suggest that benzene in blood is more reliable than phenol tests for assessing both exposure and uptake of benzene. Normal values of phenol in urine (10 mg/liter or less) were found in nearly all those cases in which benzene was detected in the blood.     

OR2W3 sequence variants are unlikely to cause inherited retinal diseases

Because of its formidable throughput, whole exome sequencing (WES) is significantly increasing the power of investigations in ophthalmic genetics. However, when applied to Mendelian conditions, WES results often contain many false positives, e.g. candidate mutations that are unrelated to the disease. For instance, highly polymorphic genes such as olfactory receptor genes carry a plethora of both common and rare alleles that are part of the normal set of variations of the human genome. Following a WES-based study, the heterozygous missense variant p.R142W in the olfactory receptor gene OR2W3 was recently reported as a pathogenic mutation causing autosomal dominant retinitis pigmentosa (RP). This variant, however, was not scored against data contained in public WES repositories, indicating that p.R142W is present in ~1 in 6500 control individuals. Therefore, if it really was pathogenic, it would be responsible for a percentage of dominant RP cases corresponding to the double of those recorded so far worldwide, or 2/3 of all RP cases (dominant, recessive, and X-linked). We therefore conclude that this sequence variant, and hence the OR2W3 gene, do not cause RP. Prompted by these findings and based on simple principles of population genetics, we suggest that WES studies should consider DNA variants as the possible cause of dominant RP only if they are present in less than 1:100,000 individuals from the general population. In addition, we propose that DNA variants belonging to highly polymorphic genes should be carefully analyzed at the functional level before inferring their pathogenicity, in RP or other genetic diseases.