TP-03. THE PREDICTIVE VALUE OF TUMOR MARKERS IN NEWLY DIAGNOSED PATIENTS WITH PRIMARY CENTRAL NERVOUS SYSTEM CNS ; GERM CELL TUMORS GCT ; AeRang Kim, Casilda Balmaceda, Blanca Diez, Stuart Kellie, Judith Villablanca, and Jonathan Finlay, for the International CNS Germ Cell Tumor Study Group; New York University School of Medicine, New York, NY; Columbia University, New York, NY, USA; Gutierrez Children's Hospital, Buenos Aires, Argentina; Children's Hospital at Westmead, Sydney, Australia; Children's Hospital of Los Angeles, Los Angeles, CA, USA; and Participating Institutions Objectives: This study was undertaken to determine the impact upon event-free and overall survivals of the presence or absence of elevated serum and or CSF alpha-fetoprotein AFP ; and or beta-human chorionic gonadotropin b-HCG ; in patients newly diagnosed with CNS GCT treated uniformly with chemotherapy. Methods: Between November 1989 and May 1997, 122 patients, newly diagnosed with primary CNS GCT, were enrolled upon two sequential internationally conducted clinical trials, employing initial chemotherapy with the intent of avoiding irradiation. Patients were treated for 4 to 6 months of chemotherapy, and have since been followed up with serial standard imaging and tumor marker evaluations. Ninety-five patients had both serum and CSF tumor markers for AFP and beta-HCG determined at initiation of treatment, while 12 patients had determination of levels in the serum but not the CSF, 3 only in the CSF, and 12 without any marker determinations at diagnosis. Tumor markers were reported to be normal in 44 patients, 39 of whom had biopsy proven germinomas. Serum and CSF AFP levels of 10 ng and b-HCG levels of 5 mIU mL were considered to be normal. Results: Of patients without tumor marker positivity at diagnosis n 44 ; , the 5-year event-free survival EFS ; and overall survival OS ; are 35 7% and 72 7%. Of patients with any tumor marker positivity at diagnosis n 66 ; , the 5-year EFS and OS are 43 6% and 70 6%. Patients with elevations of AFP only, in either serum or CSF n 33 ; , had 5-year EFS and OS of 52 10% and 63 9%. Patients with elevations of b-HCG alone in either serum or CSF n 49 ; had 5-year EFS and OS of 40 8% and 72 7%. Patients with both markers elevated in either serum or CSF n 16 ; had 5-year EFS and OS of 50 15% and 62 12%. Of patients in whom both serum and CSF marker values at diagnosis were available n 66 ; , a ratio of CSF: serum of 0.5 for any tumor marker was associated with a poorer overall survival at 5 years 57 10% ; compared with CSF: serum ratio 2.0 77 10% ; . Conclusions: A chemotherapy only treatment strategy for marker negative patients with CNS GCT results in inferior EFS and OS compared with radiation therapy containing treatments. However, patients with tumor marker positivity achieve at least as good EFS and OS with chemotherapy as the marker negative patients. A trend is observed for AFP positive patients to have a poorer OS. Surprisingly, an increased ratio of serum to CSF tumor markers appears to be associated with a more unfavorable prognosis. The impact of CSF versus serum markers on sites of recurrence will be presented, as well as the predictive value of the rate of decline of tumor markers with chemotherapy.
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A number of studies suggest a benefit of omega-3 fatty acids FAs ; in mood disorders, but it should be noted that this was generally in conjunction with existing treatments and high doses can cause a worsening of symptoms in some patients. Omega-3 FAs are polyunsaturated FAs found in cold-water oily fish and in the seeds of chia, perilla, flax, purslane, hemp and canola though fish-derived sources are better ; . While the U.S. National Institute of Health recommends 650 mg of eicosapentaenoic EPA ; and docosahexaenoic DHA ; acids day, 2.22 g day of -linolenic acid, and 4.44 g day of linoleic acid an omega-6 FA ; . Unclear are the optimal dosing and ratios of EPA: DHA and omega-6 FA: omega-3 FA. D x and calciferol.
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TABLE 99 Trichlormethiazide: comparisons with active treatment Study Comparator Type of fracture Number of subjects suffering fracture Trichlormethiazide + alfacalcidol Yamada, 198928 Aalfacalcidol alone No treatment Vertebral Vertebral 0 11 0 Comparator 3 14 2 fracture 95% CI ; : trichlormethiazide + alfacalcidol vs comparator 0.18 0.01 to 3.13 ; 0.23 0.01 to 4.40 and alpha-lipoic.
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Group 1A: 15 mg fluoride + 450 mg calcium Group 1B: 15 mg fluoride + 450 mg calcium + 0.5 g alfacalcidol Cumulative prednisone intake g ; : Year 1: Alfacalcidol: 5.3 1.8 Etidronate: 4.9 1.8 Year 2: Alfacalcidol: 1.5 0.4 Etidronate: 1.6 0.5 Calcium carbonate 1.25 g day plus an incremental dose of alfacalcidol starting dose 0.25 g day, to a maximum of 1 g day ; Calcium carbonate 1.25 g day for 11 weeks followed by etidronate 400 mg day for 2 weeks and amantadine.
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47. Moe SM, Kraus MA, Gassensmith CM, Fineberg NS, Gannon FH, Peacock M: Safety and efficacy of pulse and daily calcitriol in patients on CAPD: A randomized trial. Nephrol Dial Transplant 1998; 13: 1234-1241 Maung HM, Elangovan L, Frazao JM, Bower JD, Kelley BJ, Acchiardo SR, Rodriguez HJ, Norris KC, Sigala JF, Rutkowski M, Robertson JA, Goodman WG, Levine BS, Chesney RW, Mazess RB, Kyllo DM, Douglass LL, Bishop CW, Coburn JW: Efficacy and side effects of intermittent intravenous and oral doxercalciferol 1alphahydroxyvitamin D 2 ; in dialysis patients with secondary hyperparathyrodisim: A Sequential comparison. J Kidney Dis 2001; 37: 532-543 Brown AJ, Slatopolsky E: Vtamin D analogs: Perspectives for treatment. Miner Electrolyte Metab 1991; 25: 337-341 Slatopolsky E, Dusso A, Brown A: New analogs of vitamin D3. Kidney Int Suppl 1999; 73: S46-S51 51. Kurokawa K, Akizawa T, Suzuki M, Akiba T, Ogata E, Slatopolsky E: Effect of 22-oxacalcitriol on hyperparathyroidism of dialysis patients: Results of a preliminary study. Nephrol Dial Transplant 1996; 11: 121124, suppl 3 ; 52. Akiba T, Marumo F, Owada A, Kurihara S, Inoue A, Chida Y, Ando R, Shinoda T, Ishida Y, Ohashi Y: Controlled trial of falecalcitriol versus alfacalcidol in suppression of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism. J Kidney Dis 1998; 32: 238-246 and amiloride.
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This case illustrates a marked sustained improvement of hyperparathyroidism, with substantial decrements in PTH levels, paralleled with regression of the size and increased sclerosis of the expansile bony lesions carefully documented by serial CT scans after treatment with both oral cholecalciferol and alfacalcidol. Reports of patients with primary hyperparathyroidism and osteitis fibrosa cystica revealed substantial increments in BMD at the spine, hip, and forearm by 100 550% after parathyroidectomy 5, 7 ; . Kulak et al. showed normalization of T scores in two young patients with severe primary hyperparathyroidism 5 ; . Our patient had substantial increment in BMD at the spine and the hip at 1 and 2 yr of therapy, but there was no response at the forearm. The absence of response at the forearm in this case as opposed to the increment observed in the two other studies may be in part explained by the substantially higher PTH levels in the reported cases.
Division of Nuclear Medicine, Department of Radiology and Department of Pathology, Campinas State University, Campinas, Brazil. Correspondence to: Elba Cristina S de Camargo Etchebehere, Servio de Medicina Nuclear do Hospital das Clnicas da UNICAMP, Caixa postal 6142, 13081-970 Campinas, SP, Brazil. Phone : + 55-19-2895973. Fax : + 55-19-2511041. e-mail: elba mn-d.
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Confirmed the cell type-specific differences of receptor expression by Western blot analysis. Figure 4A lower panel ; shows that the 77-kDa YFP-RXR immunoreactivity is much stronger in CYR cells than in RYRXR cells. Next, we compared the expression level of GFP-VDR in RGVDR cells with the expression level 0.1% of the of GFP-VDR in GL48 cells. Only 0.7 RGVDR cells contained detectable levels of GFP-VDR fluorescence, even after three subsequent cycles of and calciferol.
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The incidence of purulent infections has not increased in the herd since the last health monitoring report. However, at the semi-annual health monitoring in spring 2004, nasal swabs of the Gttingen minipigs turned out positive for haemolytic streptococci. Species identification of the positive sample verified the diagnosis of one animal from Barrier 2. The haemolytic streptococcus was identified as a Str. dysgalactiae subsp. equisimilis. Skin scrapings examined for bacterial pathogens from the pigs tested at EGM did not test positive for haemolytic streptococci. No other changes in health status were discovered. Streptococci are Gram-positive cocci, which are seen as commensals in warm-blooded animals. Streptococci can be classified into different groups according to which kind of haemolysis is seen on blood agar. Str. dysgalactiae belongs to the pyogenic b-haemolytic streptococci and contains Lancefield group A, C, G and L antigens. Infection with pyogenic streptococci can cause arthritis, metritis, endocarditis or septicaemia. Str. dysgalactiae is divided into two subspecies; Str. dysgalactiae subsp. dysgalactiae and Str. dysgalactiae subsp. equisimilis based on protein profile and biochemical properties Vandamme, P. et al, 1996 ; Str. dysgalactiae subsp. equisimilis is part of the normal commensal flora of the skin and mucosa in the nose and pharynx of humans and many animal species such as cattle, dogs, cats, pigs and poultry, and is not a frequent cause of the above-mentioned purulent infections. Streptococci of many serological groups are frequently isolated from nasal and pharyngeal secretions of swine. These infections are not known to be associated with disease of the upper respiratory tract Sanford, S.E. & Higgins, R. ; . Since Str. dysgalactiae subsp. equisimilis is part of the normal mucosal and skin flora of humans, the most likely source of contamination is from one of the staff members. Staff members shower in when entering the barriers.A second washing and disinfection of the hands is performed before entry. This can minimize the risk of transferring commensals from the skin of humans to the minipigs, but not remove it completely. References: Larsen, H.E., 1996, "Streptokokker og beslgtede kokker", in Larsen, H.E & Aalbk, B., "Veterinr mikrobiologi" ; , Jordbrugsforlaget, Frederiksberg C, Denmark, pp. 1.18-1.34 Sanford, S.E. & Higgins, R., 1992, "Streptococcal Diseases", in "Diseases of Swine 7th edition", eds. Leman, A.D., Straw, N.E., Mengeling, W.L., D'Allaire, S., Taylor, D ; , Iowa State University Press, Ames, Iowa, USA Vandamme, P., Pot, B., Falsen, E., Kersters, K., Devriese, L.A., 1996, "Taxonomic study of Lancefield groups C, G, and L!
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