No abstract

Herpes simplex virus thymidine kinase (HSV tk) gene therapy combined with ganciclovir (GCV) medication is a potential new method for the treatment of malignant glioma. We have used both retrovirus-packaging cells (PA317/tk) and adenoviruses (Adv/tk) for gene therapy for malignant glioma. Retrovirus-packaging cells were used for eight tumors in seven patients and adenoviruses were used for seven tumors in seven patients. As a control group, seven tumors in seven patients were transduced with lacZ marker gene 4-5 days before tumor resection. Safety and efficacy of the gene therapy were studied with clinical evaluation, blood and urine samples, MRI follow-up, and survival of the patients. Four patients with adenovirus injections had a significant increase in anti-adenovirus antibodies and two of them had a short-term fever reaction. Frequency of epileptic seizures increased in two patients. No other adverse events possibly related to gene therapy were detected. In the retrovirus group, all treated gliomas showed progression by MRI at the 3-month time point, whereas three of the seven patients treated with Adv/tk remained stable (p < 0.05). Mean survival times for retrovirus, adenovirus, and control groups were 7.4, 15.0, and 8. 3 months, respectively. The difference in the survival times between the adenovirus and retrovirus groups was significant (p < 0.012). It is concluded that HSV tk gene therapy is safe and well tolerated. On the basis of these results further trials are justified, especially with adenovirus vectors.

Renal osteodystrophy alters metabolic activity and remodeling rate of bone and also may lead to different bone composition. The objective of this study was to characterize the composition of bone in high-turnover renal osteodystrophy patients by means of Fourier transform infrared spectroscopic imaging (FTIRI). Iliac crest biopsies from healthy bone (n ¼ 11) and patients with renal osteodystrophy (ROD, n ¼ 11) were used in this study. The ROD samples were from patients with hyperparathyroid disease. By using FTIRI, phosphate-toamide I ratio (mineral-to-matrix ratio), carbonate-to-phosphate ratio, and carbonate-to-amide I ratio (turnover rate/remodeling activity), as well as the collagen cross-link ratio (collagen maturity), were quantified. Histomorphometric analyses were conducted for comparison. The ROD samples showed significantly lower carbonate-to-phosphate ( p < .01) and carbonate-to-amide I ( p < .001) ratios. The spatial variation across the trabeculae highlighted a significantly lower degree of mineralization ( p < .05) at the edges of the trabeculae in the ROD samples than in normal bone. Statistically significant linear correlations were found between histomorphometric parameters related to bone-remodeling activity and number of bone cells and FTIRI-calculated parameters based on carbonate-to-phosphate and carbonate-to-amide I ratios. Hence the results suggested that FTIRI parameters related to carbonate may be indicative of turnover and remodeling rate of bone. ß 2010 American Society for Bone and Mineral Research.KEY WORDS: BONE COMPOSITION; HISTOMORPHOMETRY; FOURIER TRANSFORM; INFRARED; RENAL OSTEODYSTROPHY; CARBONATE B one is a composite material consisting of a mineral phase (hydroxyapatite), an organic phase (collagen), noncollagenous proteins, lipids, and water. (1,2) Metabolic bone disease is a common term referring to a number of abnormalities caused by a broad spectrum of disorders. Most disorders lead to weakening of the bone or impaired bone function and are followed most often by altered bone mechanical properties. Renal osteodystrophy (ROD) is a chronic kidney disease that can be accompanied by different types of bone pathologies. ROD can lead to defective mineralization, altered bone morphology, and/or bone turnover. (3,4) Commonly, it is accompanied by hyperparathyroid disease, which is characterized by increased bone turnover. Patients with renal osteodystrophy may exhibit bone and joint pain, bone deformation, and spontaneous bone fractures. Bone biopsies followed by quantitative histomorphometry prevail as the ''gold standard'' for the diagnosis of renal osteodystrophy. (5)(6)(7) Histomorphometric analysis emphasizes increased amounts of osteoid and erosion surface and a larger amount of bone cells than what is present in normal bone. (8) However, the invasive nature of obtaining the biopsies, the required experience of the pathologists to identify the abnormalities, as well as the lack of standardized normal limits remain problematic.ROD also commonly results in lower bone ...

No abstract