Cyclic changes in blood serum cholesterol and protein concentrations in the course of hypercholesterolemia

Laboratory of Biochemistry, Research Institute of Neurology and Psychiatry, Khar'kov. (Presented by Academician of the Academy of Medical Sciences of the USSR A. A. Korzh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 3, pp. 259–261, March, 1992.     

Pulmonary resection of arteriovenous fistula

Arteriovenous fistula (AVF) is rare congenital pathology of the bronchopulmonary system vessels. The results of treatment of 12 patients with AVF were analyzed. In 2 (16.6%) patients Randu-Veber-Osler syndrome was diagnosed. In 10 observations the diagnosis was confirmed by the angiography data. All the patients were operated on. One (8.4%) patient died.     

Carcinosarcoma: a rare mixed tumor of the bronchopulmonary system

Six patients with carcinosarcoma were observed in the clinic. In 4 patients with roentgenological signs of tumor were determined and in 2--the signs of pleuritis. The diagnosis was established after pulmonary resection performance or after thoracoscopy with pleural biopsy conduction.     

Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells

Background

Tumor Treating Fields (TTFields) are an anti-neoplastic treatment modality delivered via application of alternating electric fields using insulated transducer arrays placed directly on the skin in the region surrounding the tumor. A Phase 3 clinical trial has demonstrated the effectiveness of continuous TTFields application in patients with glioblastoma during maintenance treatment with Temozolomide. The goal of this study was to evaluate the efficacy of combining TTFields with radiation treatment (RT) in glioma cells. We also examined the effect of TTFields transducer arrays on RT distribution in a phantom model and the impact on rat skin toxicity.

Methods

The efficacy of TTFields application after induction of DNA damage by RT or bleomycin was tested in U-118 MG and LN-18 glioma cells. The alkaline comet assay was used to measure repair of DNA lesions. Repair of DNA double strand breaks (DSBs) were assessed by analyzing γH2AX or Rad51 foci. DNA damage and repair signaled by the activation pattern of phospho-ATM (pS1981) and phospho-DNA-PKcs (pS2056) was evaluated by immunoblotting. The absorption of the RT energy by transducer arrays was measured by applying RT through arrays placed on a solid-state phantom. Skin toxicities were tested in rats irradiated daily through the arrays with 2Gy (total dose of 20Gy).

Results

TTFields synergistically enhanced the efficacy of RT in glioma cells. Application of TTFields to irradiated cells impaired repair of irradiation- or chemically-induced DNA damage, possibly by blocking homologous recombination repair. Transducer arrays presence caused a minor reduction in RT intensity at 20 mm and 60 mm below the arrays, but led to a significant increase in RT dosage at the phantom surface jeopardizing the “skin sparing effect”. Nevertheless, transducer arrays placed on the rat skin during RT did not lead to additional skin reactions.

Conclusions

Administration of TTFields after RT increases glioma cells treatment efficacy possibly by inhibition of DNA damage repair. These preclinical results support the application of TTFields therapy immediately after RT as a viable regimen to enhance RT outcome. Phantom measurements and animal models imply that it may be possible to leave the transducer arrays in place during RT without increasing skin toxicities.

     

Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study

OBJECTIVE: The objective of this Phase 3 study was to confirm the efficacy and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome), a rare, fatal lysosomal storage disease with no effective treatment. STUDY DESIGN: Thirty-nine patients with MPS VI were evaluated in a randomized, double-blind, placebo-controlled, multicenter, multinational study for 24 weeks. The primary efficacy variable was the distance walked in a 12-minute walk test (12MWT), whereas the secondary efficacy variables were the number of stairs climbed in a 3-minute stair climb (3MSC) and the level of urinary glycosaminoglycan (GAG) excretion. All patients received drug in an open-label extension period for an additional 24 weeks. RESULTS: After 24 weeks, patients receiving rhASB walked on average 92 meters (m) more in the 12MWT (p=.025) and 5.7 stairs per minute more 3MSC (p=.053) than patients receiving placebo. Continued improvement was observed during the extension study. Urinary GAG declined by -227+/-18 microg/mg more with rhASB than placebo (p<.001). Infusions were generally safe and well tolerated. Patients exposed to drug experienced positive clinical benefit despite the presence of antibody to the protein. CONCLUSION: rhASB significantly improves endurance, reduces GAG, and has an acceptable safety profile.     

Surgical treatment of chronic purulent diseases of extremities' bones and great joints

Results of treatment of chronic purulent diseases of extremities' bones (n=414) and great joints (n=136) were analyzed. Combined treatment included surgical sanation of the inflammatory focus, autospongioplasty of residual cavities and defects after sequesterectomy (87 cases), extrafocal osteosynthesis, aspiration- flushing drainage. In 46 cases of severe suppuration in the zone of hip joint's endoprosthesis the resection arthroplasty was performed, in 43 cases of severe consequences of ankle-joint's fracture-dislocations -- compression talo-tibial and calcaneo-tibial arthrodesis. The follow-up was 15 years. Positive results were seen in 93.6% patients.