Database: EMBASE <: international biomedical and pharmaceutical literature, 1988 - Jun 2000. [Trial access until 3/2001. Feedback welcome to medical.library@umich.edu] Search Strategy (You Saved Citations 1-122 From Set 64): ----------------------------------------------------------------------------- 1 Dental enamel/ 975 2 Dental enamel solubility/ 975 3 exp Tooth permeability/ 3 4 ((dentin or tooth or teeth or enamel) adj3 (solubility or 31 soluble or permeability or permeable)).mp. 5 exp Dentin/ 782 6 Dentin solubility/ 782 7 or/1-6 1574 8 exp Tooth demineralization/ 7624 9 demineralization.mp. 889 10 caries.mp. 1810 11 caires.mp. 0 12 craies.mp. 0 13 careis.mp. 1 14 carise.mp. 0 15 (teeth adj3 cavit:).mp. 32 16 (tooth adj3 cavit:).mp. 31 17 (dental adj3 cavit:).mp. 54 18 (dentin adj3 cavit:).mp. 14 19 (enamel adj3 cavit:).mp. 6 20 (teeth adj3 decay:).mp. 59 21 (tooth adj3 decay:).mp. 58 22 (dental adj3 decay:).mp. 47 23 (dentin adj3 decay:).mp. 0 24 (enamel adj3 decay:).mp. 1 25 (active adj decay).mp. 5 26 (rampant adj3 decay:).mp. 4 27 (recurrent adj3 decay:).mp. 3 28 (white adj spot:).mp. 226 29 carious.mp. 110 30 cariology.ti,ab. 2 31 (non-cavitated adj3 lesion:).mp. 0 32 (noncavitated adj3 lesion:).mp. 1 33 Tooth remineralization/ 800 34 (dental adj3 fissure:).mp. 7 35 (tooth adj3 fissure:).mp. 3 36 (teeth adj3 fissure:).mp. 1 37 caries-free.mp. 28 38 cariesfree.mp. 0 39 Cariogenic agents/ 3 40 precavit:.mp. 2 41 (filled adj3 teeth).mp. 46 42 (filled adj3 tooth).mp. 9 43 (oral adj fissure:).mp. 4 44 (tooth adj3 remineraliz:).mp. 1 45 (teeth adj3 remineraliz:).mp. 4 46 dft.mp. 560 47 dfs.mp. 992 48 dmf:.mp. 1254 49 cariogeni:.mp. 166 50 or/8-49 12451 51 7 or 50 13596 52 Bone morphogenetic proteins/ 1315 53 BMP$1.mp. 1728 54 Transforming growth factor beta/ 8607 55 (osteogen: adj (protein$1 or (growth adj factor))).mp. 241 56 (bone adj morphogen: adj3 (protein$1 or (growth adj 1916 factor))).mp. 57 Regeneration/ 1586 58 exp Bone remodeling/ 3196 59 ((reparat: or reaction:) adj (dentin or enamel)).mp. 16 60 exp Recombinant proteins/ 53767 61 or/52-60 68460 62 51 and 61 228 63 limit 62 to english language 221 64 limit 63 to human 122 65 from 64 keep 1-122 122 *************************** <1> UI - 2000172261 AU - Touati G AU - Ruiz J-C AU - Porquet D AU - Kindermans C AU - Prieur A-M AU - Czernichow P IN - Prof. P. Czernichow, Service Endocrinologie Pediatrique, Hopital Robert Debre, 48 Boulevard Serurier, 75019 Paris; France. TI - Effects on bone metabolism of one year recombinant human growth hormone administration to children with juvenile chronic arthritis undergoing chronic steroid therapy. SO - Journal of Rheumatology Vol 27(5) (pp 1287-1293), 2000. AB - Objective. To study the effects on bone metabolism of treatment with recombinant human growth hormone (rhGH) in children with juvenile chronic' arthritis (JCA) who are undergoing treatment with glucocorticoids (GC) and have severe bone lesions. Methods. We assessed the effects of rhGH treatment (1.4 U/kg/week) on bone metabolism markers and bone density measured during a one year treatment course in 14 patients with systemic forms of JCA undergoing long-term GC treatment. Results. All patients, at inclusion showed severe bone demineralization (mean bone density: -3.7 standard deviation score for chronological age). Compared to pretreatment values, bone formation markers (blood levels of osteocalcin and C-terminal propeptide of type 1 procollagen) and bone resorption markers (urinary hydroxyproline, pyridinoline, and deoxypyridinoline levels) increased significantly during treatment and returned to pretreatment values after discontinuation of rhGH. We observed that plasma level of osteocalcin was the best predictive variable of growth response to rhGH treatment in, these patients. Conclusion. The results reflect an increase in bone turnover in these patients. Despite these biochemical changes no improvement of bone density was observed during the one year treatment. Treatment of longer duration is necessary to evaluate the curative effects of GH. [References: 35] <2> UI - 2000164378 AU - Srivastava R AU - Srivastava BS IN - R. Srivastava, Division of Microbiology, Central Drug Research Institute, Lucknow 226 001; India. E-Mail: root@cscdri.ren.nic.in. TI - Tuberculosis vaccines: A critical role for T-cells. SO - Current Opinion in Anti-Inflammatory & Immunomodulatory Investigational Drugs Vol 2(2) (pp 100-107), 2000. <3> UI - 2000126307 AU - Fountzilas G AU - Zisiadis A AU - Dafni U AU - Konstantaras C AU - Hatzitheoharis G AU - Papavramidis S AU - Bousoulegas A AU - Basdanis G AU - Giannoulis E AU - Dokmetzioglou J AU - Katsohis C AU - Nenopoulou E AU - Karvounis N AU - Briassoulis E AU - Aravantinos G AU - Kosmidis P AU - Skarlos D AU - Pavlidis N IN - Dr. G. Fountzilas, Hellenic Cooperative Oncology Group, 1 Laskaridou Street, GR-Athens 11524; Greece. E-Mail: fountzil@med.auth.gr. TI - Fluorouracil and leucovorin with or without interferon alfa-2a as adjuvant treatment, in patients with high-risk colon cancer. A randomized phase III study conducted by the Hellenic Cooperative Oncology Group. SO - Oncology Vol 58(3) (pp 227-236), 2000. AB - Background: It has been shown in randomized studies that adjuvant treatment with the combination of fluorouracil (FU) and levamisole reduced the risk of recurrence and deaths of patients with stage III colon cancer. Pharmacological studies of FU led to its use in combination with a number of modulating agents including interferon-alpha and leucovorin (LV) that appear to enhance its activity in vitro. Furthermore, a meta-analysis suggested that the combination of FU with LV increased the response rate as compared to FU monotherapy in patients with advanced colorectal cancer. Purpose: To evaluate the impact of adjuvant treatment with the combination of FU and LV with or without interferon alfa-2a (IFN) on disease-free survival (DFS) and overall survival (OS) for patients with stage II or III colon cancer. Patients and Methods: From August 1989 to July 1997, 280 patients with stage II and III colon cancer entered the study and were randomly assigned to receive either the combination of FU (600 mg/m2/week x 6, followed by a 2-week rest) and LV (500 mg/m2/week x 6 as a 2-hour infusion, followed by a 2-week rest) for 4 cycles (group A, 139 patients), or the same chemotherapy plus recombinant IFN (3 MU subcutaneously 3 times a week) for 1 year (group B, 141 patients). Results: A total of 109 patients (78.9%) of group A and 119 (84.4%) of group B completed four cycles of chemotherapy. Also, 51.4% of patients of group A and 53.9% of group B received >= 80% of the planned dose of FU. One patient (group A) was found to be ineligible and was not included in the analysis. The median relative dose intensity of FU in the two groups was 0.90 and 0.85, respectively. As of August 1998, after a median follow up of 4 years, there was no significant difference in either 3-year DFS (group A, 83.1%; group B, 75.9%, p = 0.14) or OS (group A, 84.5%; group B, 80.0%, p = 0.27). In the Cox model, stage of disease, number of infiltrated nodes, tumor grade and presence of regional implants were identified as significant prognostic factors for OS. Grade 3-4 toxicities, mainly diarrhea, were observed in 26.1% of patients of group A and in 24.8% of group B. There were no treatment-related deaths. Conclusions: The addition of IFN to the combination of FU with LV postoperatively does not improve DFS and OS of patients with stage II or III colon cancer. Copyright (C) 2000 S. Karger AG, Basel. [References: 43] <4> UI - 2000066892 AU - Liu B AU - Rayment SA AU - Gyurko C AU - Oppenheim FG AU - Offner GD AU - Troxler RF IN - R.F. Troxler, Department of Biochemistry, Boston University School of Medicine, Boston University Medical Center, Boston, MA 02118; United States. E-Mail: btrox@bu.edu. TI - The recombinant N-terminal region of human salivary mucin MG2 (MUC7) contains a binding domain for oral Streptococci and exhibits candidacidal activity. SO - Biochemical Journal 01 FEB 2000Vol 345(3) (pp 557-564), 2000. AB - MG2 (the MUC7 gene product) is a low-molecular-mass mucin found in human submandibular/sublingual secretions. This mucin is believed to agglutinate a variety of microbes and thus is considered an important component of the non-immune host defence system in the oral cavity. We have shown that MUC7 can bind to cariogenic strains of Streptococcus mutans and that this binding requires a structural determinant in the N-terminal region. In the present study an expression construct, pNMuc7, encoding the N-terminal 144 amino acids of MUC7 was generated, and the recombinant protein rNMUC7 was expressed in Escherichia coli. Purified rNMUC7 was characterized and the binding of this protein to oral bacteria was investigated in an established assay. The results showed that the recombinant protein bound to S. mutans ATCC 25175 and ATCC 33402, and that alkylation of the two cysteine residues (Cys45 and Cys50) resulted in the complete loss of bacterial binding. This suggests that binding of MUC7 to S. mutans occurs between the N-terminal region of the mucin molecule and the bacterial surface, and that this interaction is dependent on a cysteine-containing domain within this region of MUC7. In addition, the killing activity of rNMUC7 was compared with that of the candidacidal salivary protein histatin 5 in an established Candida albicans (ATCC 44505) blastoconidia killing assay. It was found that the LD50 values of rNMUC7 and histatin 5 were comparable, and that the recombinant protein displayed significant killing activity at the physiological concentration range of MUC7 in whole saliva. This study is the first to show that the N-terminal region of MUC7 contains a structural determinant for bacterial binding and that this region exhibits candidacidal activity. [References: 38] <5> UI - 2000049818 AU - Aoyagi T AU - Yamazaki K AU - Kabasawa-Katoh Y AU - Nakajima T AU - Yamashita N AU - Yoshie H AU - Hara K IN - K. Yamazaki, Department of Periodontology, Niigata University, Faculty of Dentistry, 5274 Gakko-cho-Dori 2-ban-cho, Niigata 951-8514; Japan. E-Mail: kaz@dent.niigata-u.ac.jp. TI - Elevated CTLA-4 expression on CD4 T cells from periodontitis patients stimulated with Porphyromonas gingivalis outer membrane antigen. SO - Clinical & Experimental Immunology Vol 119(2) (pp 280-286), 2000. AB - To characterize the T cell response to Porphyromonas gingivalis, we examined the expression of costimulatory molecules on T cells derived from adult periodontitis patients with high serum antibody titre to P. gingivalis. The expression of CD28, CTLA-4, CD40 ligand (CD40L) on CD4+ T cells was analysed by flow cytometry. IL-10 and transforming growth factor-beta (TGF- beta) mRNA expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and subsequent image analysis. Peripheral blood mononuclear cells (PBMC) derived from periodontitis patients showed higher proliferative responses to P. gingivalis outer membrane (OM) than those from healthy controls (P < 0.05). The percentage of CTLA-4+ cells within CD4+ T cells of patients was significantly higher than that of healthy controls after P. gingivalis OM stimulation (33.0% versus 11.9%, P < 0.01). There was no significant difference in the percentages of CD28+ cells and CD40L+ cells, and the percentage of CD40L+ cells was low in both groups even after stimulation. Stimulation of PBMC with P. gingivalis OM induced significantly higher IL-10 mRNA expression in periodontitis patients than in healthy controls (P < 0.05). The level of TGF-beta mRNA expression of patients tended to be higher than that of healthy controls, but there was no significant difference. To elucidate the functional role of CTLA-4, we further investigated the secondary proliferative response to P. gingivalis OM. Interestingly, P. gingivalis OM stimulation did not enhance antigen-specific secondary response. Anti-CTLA-4 MoAb had no effect on proliferation in the presence of P. gingivalis OM. CTLA-4Ig suppressed the proliferative response significantly (P < 0.01). These results suggest that T cell responses to P. gingivalis OM may be regulated by CTLA-4 that is expressed at the late phase of T cell activation, and, in part, immunosuppressive cytokines. Taken together, CTLA-4 may play a crucial role in the pathogenesis of chronic inflammatory periodontal disease. [References: 33] <6> UI - 2000028755 AU - Vijayan A AU - Behrend T AU - Miller SB IN - Dr. S.B. Miller, Renal Division, Box 8126, Washington Univ. School of Medicine, 660 S Euclid Avenue, St. Louis, MO 63110; United States. E-Mail: SBM9080@bjcmail.carenet.org. TI - Clinical use of growth factors in chronic renal failure. SO - Current Opinion in Nephrology & Hypertension Vol 9(1) (pp 5-10), 2000. AB - Erythropoietin has been demonstrated to improve the quality of life in patients with chronic renal failure, and growth hormone has been approved for use in children with chronic renal failure and short stature as a growth promoting agent. Growth factors also have great therapeutic potential to improve glomerular function in the setting of chronic renal failure. Further studies are required to delineate the role of insulin-like growth factor I in the setting of end-stage chronic renal failure. [References: 49] <7> UI - 1999430159 AU - Cassidy JT IN - Dr. J.T. Cassidy, Department of Child Health, University of Missouri, Columbia, MO 65212; United States. E-Mail: cassidyJ@missouri.edu. TI - Medical management of children with juvenile rheumatoid arthritis. SO - Drugs Vol 58(5) (pp 831-850), 1999. AB - One of the most important and changing areas of research in paediatric rheumatology is the optimum approach to the treatment of children with chronic arthritis. Until recently all medications for children with arthritis were nonspecific in terms of our understanding, albeit poor, of the pathogenesis of these diseases. Of current therapies, low dose, once-a-week methotrexate has emerged as the therapeutic agent of choice for children who fail to respond adequately to administration of a nonsteroidal anti-inflammatory drug. Thereby, it has displaced the more traditional slower acting anti-rheumatic drugs, although one or more of them are often combined with methotrexate in the polypharmaceutical approach to childhood arthritis. Better and more specific agents are needed, especially for systemic onset disease, unremitting polyarticular involvement, and certain complications such as resistant chronic uveitis. At this time the introduction of the cyclo-oxygenase 2 inhibitors and etanercept (soluble tumour necrosis factoralpha.p75 fusion protein) may herald an era of more specific and effective therapy. [References: 202] <8> UI - 1999384558 AU - Fisher B AU - Anderson S AU - DeCillis A AU - Dimitrov N AU - Atkins JN AU - Fehrenbacher L AU - Henry PH AU - Romond EH AU - Lanier KS AU - Davila E AU - Kardinal CG AU - Laufman L AU - Pierce HI AU - Abramson N AU - Keller AM AU - Hamm JT AU - Wickerham DL AU - Begovic M AU - Tan-Chiu E AU - Tian W AU - Wolmark N IN - Dr. B. Fisher, Natl. Surg. Adj. Breast/Bowel Proj., Allegheny Univ. of the Hlth. Sci., 4 Allegheny Center, Pittsburgh, PA 15212-5234; United States. E-Mail: bernard.fisher@nsabp.org. TI - Further evaluation of intensified and increased total dose of cyclophosphamide for the treatment of primary breast cancer: Findings from National Surgical Adjuvant Breast and Bowel Project B-25. SO - Journal of Clinical Oncology Vol 17(11) (pp 3374-3388), 1999. AB - Purpose: In 1989, the National Surgical Adjuvant Breast and Bowel Project initiated the B-22 trial to determine whether intensifying or intensifying and increasing the total dose of cyclophosphamide in a doxorubicin-cyclophosphamide combination would benefit women with primary breast cancer and positive axillary nodes. B-25 was initiated to determine whether further intensifying and increasing the cyclophosphamide dose would yield more favorable results. Patients and Methods: Patients (n = 2,548) were randomly assigned to three groups. The dose and intensity of doxorubicin were similar in all groups. Group 1 received four courses, ie, double the dose and intensity of cyclophosphamide given in the B-22 standard therapy group; group 2 received the same dose of cyclophosphamide as in group 1, administered in two courses (intensified); group 3 received double the dose of cyclophosphamide (intensified and increased) given in group 1. All patients received recombinant human granulocyte colony-stimulating factor. Life-table estimates were used to determine disease-free survival (DFS) and overall survival. Results: No significant difference was observed in DFS (P = .20), distant DFS (P = .31), or survival (P = .76) among the three groups. At 5 years, the DFS in groups 1 and 2 (61% v 64%, respectively; P = .29)was similar to but slightly lower than that in group 3 (61% v 66%, respectively; P = 08). Survival in group 1 was concordant with that in groups 2 (78% v 77%, respectively; P = .71) and 3 (78% v 79%, respectively; P = .86). Grade 4 toxicity was 20%, 34%, and 49% in groups 1,2, and 3, respectively. Severe infection and septic episodes increased in group 3. The decrease in the amount and intensity of cyclophosphamide and delays in therapy were greatest in courses 3 and 4 in group 3. The incidence of acute myeloid leukemia increased in all groups. Conclusion: Because intensifying and increasing cyclophosphamide two or four times that given in standard clinical practice did not substantively improve outcome, such therapy should be reserved for the clinical trial setting. [References: 36] <9> UI - 1999360751 AU - Soory M AU - Virdi H IN - Dr. M. Soory, Department of Periodontology, GKT Dental Institute, King's College, Caldecot Road, London SE5 9RW; United Kingdom. TI - Implications of minocycline, platelet-derived growth factor, and transforming growth factor-beta on inflammatory repair potential in the periodontium. SO - Journal of Periodontology Vol 70(10) (pp 1136-1143), 1999. AB - Background: Semisynthetic tetracyclines used in the adjunctive treatment of inflammatory periodontal disease enhance collagen expression in induced periodontal lesions of rats. Polypeptide growth factors regulate key cellular events in tissue repair. The physiologically active androgen 5alpha- dihydrotestosterone (DHT) stimulates bone and connective tissue turnover. It was relevant to study the effects of transforming growth factor beta (TGF- beta)/platelet-derived growth factor (PDGF) and minocycline alone and in combination on the formation of biologically effective androgens which can influence repair. Methods: Confluent monolayer cultures of human gingival fibroblasts of the fifth through the ninth passage were incubated in Eagle's minimum essential medium, with 14C-testosterone/14C-4-androstenedione in the presence of optimal concentrations of TGF-beta/PDGF/minocycline (M), alone and in combination. At the end of a 24-hour incubation period, the medium was analyzed for steroid metabolites and quantified using a radioisotope scanner. Results: The androgen substrates 14C-testosterone (14C-T) and 14C-4- androstenedione (14C-4-A) were metabolized to DHT and 4- androstenedione/testosterone respectively. There were significant increases in the formation of DHT from 14C-T in response to M, TGF-beta, and PDGF, alone and in combination (13 to 48%), compared with controls (n = 4; P <0.01). The yields of 4-androstenedione were also greater in response to these agents (31%; 3-fold). When 14C-4-A was used as substrate, there were 21 to 80% increases in the formation of DHT in response to these agents alone and in combination (n = 4; P <0.01). Conclusions: The biologically effective androgen metabolites formed in response to minocycline. TGF-beta, and PDGF can contribute to reparatory events in the flamed periodontium. Judicious, adjunctive usage of the chemically-modified tetracyclines in the treatment of periodontal diseases can obviate the risk of microbial resistance, with potential applications of their anti-inflammatory and proanabolic effects in regenerative technology. [References: 37] <10> UI - 1999356066 AU - De La Rubia J AU - Sanz GF AU - Martin G AU - Martinez J AU - Cervera J AU - Solves P AU - Jimenez C AU - Arnao M AU - Vicente A AU - Jarque I AU - Sempere A AU - Sanz MA IN - Dr. M.A. Sanz, Servicio de Hematologia, Hospital Universitario La Fe, Avenida Campar 21, 46009 Valencia; Spain. E-Mail: msanz@uv.es. TI - Autologous blood stem cell transplantation for acute myeloblastic leukemia in first complete remission. Intensification therapy before transplantation does not prolong disease-free survival. SO - Haematologica Vol 84(2) (pp 125-132), 1999. AB - Background and Objective. To compare the clinical results of two consecutive therapeutic protocols including autologous blood stem cell transplantation (ABSCT) for patients with de novo acute myeloblastic leukemia (AML) in first complete remission (CR1). Design and Methods. Between November 1989 and January 1997, 50 patients with AML in CR1 underwent ABSCT using two consecutive protocols. In the first one (Group A, 25 patients) peripheral blood stem cells (PBSC) were collected after induction and consolidation chemotherapy courses, and ABSCT was performed immediately thereafter. In the subsequent 25 patients (Group B), PBSC were collected after consolidation alone, and a further chemotherapy course with intermediate dose cytarabine (Ara-C 1g/m2/12h x 3 days) and mitoxantrone (12 mg/m2/d x 3 days) was administered as early intensification. The conditioning regimen consisted of busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) in every case. Results. Hematopoietic engraftment was slightly quicker in Group B, with median times to reach 0.5x109 neutrophils/L and 20x109 platelets/L being 13 and 12 days in Group A and 12 and 11 days in Group B, respectively. There were three graft failures (8%) (2 in Group A and I in Group B) and three transplant- related deaths (8%) (2 in Group A and I in Group B). No significant differences were observed between the groups in terms of relapse (64% at 4- years in Group A and 81% in Group B). Likewise, the actuarial 4-year disease- free survival (DFS) was not significantly different between the two groups (32% v 18%). Interpretation and Conclusions. Our study confirms that AML patients in CR1 receiving ABSCT have rapid engraftment with low mortality. However, autologous transplants with PBSC collected after consolidation chemotherapy were still associated with a high rate of relapse (RR). This RR was not apparently reduced by the administration of intermediate dose Ara-C before transplantation. [References: 40] <11> UI - 1999349946 AU - Sandhu HS AU - Grewal HS AU - Parvataneni H IN - Dr. H.S. Sandhu, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021; United States. TI - Bone grafting for spinal fusion. SO - Orthopedic Clinics of North America Vol 30(4) (pp 685-698), 1999. AB - At least 250,000 spinal fusions are performed in the United States each year, nearly all requiring implantation of bone graff material. The preferred technique for most of these operations is the transplantation of structured or morcellized autologous corticocancellous bone from the iliac crest. Further, because of the increasing frequency of spinal fusion surgery during the 1990s, arthrodesis of the spine has become the most common reason for autologous bone graft harvest. This article reviews the current clinical status of autogenous bone grafts and alternative materials in spinal fusion surgery. [References: 94] <12> UI - 1999286675 AU - Tarumi T AU - Sawada K-I AU - Koizumi K AU - Takano H AU - Fukada Y AU - Nishio M AU - Fujie T AU - Ohnishi K AU - Kohno M AU - Sato N AU - Sekiguchi S AU - Koike T IN - Dr. K.-I. Sawada, Department of Internal Medicine II, Hokkaido University, School of Medicine, N-15, N-7, Kita-ku, Sapporo 060; Japan. E-Mail: ksawada@med.hokudai.ac.jp. TI - A pilot study of a response oriented chemotherapeutic regimen combined with autologous peripheral blood progenitor cell transplantation in aggressive non-Hodgkin's lymphoma. SO - Leukemia & Lymphoma Vol 34(3-4) (pp 361-371), 1999. AB - Fourteen consecutive patients with poor-risk aggressive NHL who at presentation had any one of four risk factors underwent response oriented induction chemotherapy and successive high-dose chemotherapy followed by autologous PBPC transplantation. After treatment with three cycles of conventional CHOP with G-CSF support (CHOP-G), the response was evaluated. For patients who achieved a complete remission (CR), an additional three cycles of CHOP-G were administered, while for partial response patients, another induction regimen including some non-cross-resistant agents was given; three cycles of VIPDexa-G (etoposide, ifosfamide, cisplatinum and dexamethasone) +/- two cycles of ENAP-G (mitoxantrone, etoposide, cytosine arabinoside and prednisone), were given. The scheduled induction chemotherapy, was followed by treatment with a high-dose cytoreductive regimen followed by autologous PBPC transplantation. After three cycles of CHOP-G, four patients (29%) achieved a CR, and 10 (71%) achieved a partial response (PR). When all scheduled induction therapy was completed, 10 patients (71%) had a CR. All 14 patients received high-dose therapy and obtained a complete hematologic recovery, except for one with a bone marrow relapse two months after transplantation. Evaluation of response after high-dose therapy showed 12 CRs (86%) which included three additional CRs, one PR, and one toxicity-related death. With a median follow-up of 12 months (range, 4 to 40), 12 are alive, with 11 in continuous first CR, and one relapse. The 2-year overall survival (OS) rate and event-free survival (EFS) rate are 77% and 79%, respectively, while the disease-free survival (DFS) rate is 92%. In conclusion, this pilot study suggests that response oriented induction chemotherapy and successive high-dose chemotherapy followed by autologous PBPC transplantation is commendable and can be associated with a high rate of remission and DFS for poor risk subjects with aggressive NHL. [References: 24] <13> UI - 1999267456 AU - Laroche M AU - Ludot I AU - Brousset P AU - Mazieres B IN - Dr. M. Laroche, Service de Rhumatologie, Centre Hospitalier, Universitaire Rangueil, 1 avenue Jean Poulhes, F-31403 Toulouse Cedex 4; France. TI - Osteoporosis with lymphoid nodules and hematopoietic marrow hyperplasia. SO - Clinical & Experimental Rheumatology Vol 17(4) (pp 457-460), 1999. AB - Objective: In 1983 Vigorita reported 3 cases of osteoporosis associated with intramedullary lymphoid nodules. We present 8 patients with osteoporosis and lymphoid nodules (LN) in whom we studied the clinical, biological and histological features and the course of the disease. Methods: Three men (mean age 52 yrs., range 43-68 yrs.) and 5 women (mean age 60 yrs., 49-66 yrs.), 6 of them with osteoporosis with fracture and 2 with osteoporosis on bone densitometry (T score < -2.5 SD) were enrolled in this study. The following parameters were studied: immunobinding with IG determination, phosphorus and calcium levels, PTH, 25 and 1-25 OH D3, osteocalcin, urinary deoxypyridinoline, histomorphometry, tests for autoantibodies, HIV, HTLV, EBV and CMV serology. The results were compared with those of 20 patients with osteoporosis but without LN. Five patients underwent a second BMB a mean of 2 years after the first. Results: Five patients had asthenia, 4 had joint pain and 3 had hyperlymphocytosis. Immunologic and virologic investigations were negative in all cases. Bone marrow was hypercellular (59.9 +/- 5.3 vs 40.1 +/- 13%, p : 0.001). At the second BMB, LN were absent but bone marrow was still hypercellular. In all cases, no cause of demineralization was found and osteoporosis progressed rapidly (an average of 3 vertebral compression fractures in three months, with increased resorption (ES 6.5 +/- 1.6 vs 3 +/- 1.2, p : 0.05) with decreased calcification rate (CR 0.62 +/- 0.07 vs 0.79 +/- 0.1, p : 0.04). Conclusion: Some interesting questions are raised by this study. Did an undiscovered viral infection cause the asthenia and joint pain via cytokines or PTHrp in our patients, and can activated lymphocytes perhaps modify bone remodeling?. [References: 15] <14> UI - 1999220303 AU - Bouabdallah R AU - Stoppa A-M AU - Rossi J-F AU - Lepeu G AU - Coso D AU - Xerri L AU - Ladaique P AU - Chabannon C AU - Blaise D AU - Bardou V-J AU - Alzieu C AU - Gastaut J-A AU - Maraninchi D IN - R. Bouabdallah, Department of Hematology, Institut Paoli-I Calmettes, 232 Boulevard Sainte-Marguerite, 13273 Marseille Cedex 09; France. TI - Intensive sequential chemotherapy (ISC 95) with growth factors and blood stem cell support in high-intermediate and high-risk (IPI 2 and IPI 3) aggressive non-Hodgkin's lymphoma: An oligocentric report on 42 patients. SO - Leukemia Vol 13(6) (pp 950-956), 1999. AB - We previously reported feasibility and efficacy of a monocentric pilot study of intensive sequential chemotherapy (ISC) in poor-risk aggressive non-Hodgkin's lymphoma (NHL) in patients < 60 years. To validate these results on a large cohort of patients, we designed a new and oligocentric study. After a COP (cyclophosphamide (Cy), vincristine (Ver), prednisone (Pred) debulking, patients received four courses of high-dose CHOP (Cy, doxorubicin (Doxo), Ver, Pred), with the addition of etoposide and cisplatin during the two last courses. G-CSF was delivered after each cycle, and peripheral blood stem cells (PBSC) were used to support the two last cycles. Total duration of chemotherapy was 13 weeks, with a planned dose-intensity (DI) of 1420 mg/m2/week and 23 mg/m2/week for Cy and Doxo, respectively. Radiotherapy (involved fields) was then delivered for patients with node site >= 5 cm at diagnosis. Forty-two patients were enrolled in this study; 36 completed the treatment and received 75% or more of the planned DI for both Cy and Doxo. Median duration of grade 4 neutropenia was 14 days (range, 2 to 28) for the regimen as a whole, and median duration of rehospitalization for febrile neutropenia was 18 days (range, 4 to 41). Overall response rate was 83%, with 29 patients (69%) in complete response (CR). Six patients failed to respond and one died of toxicity. With a median follow-up of 22.5 months (range, 10 to 42), the 3-year event-free survival (EFS) is 55% (95% CI, 39-71), while disease-free survival (DFS) is 79% (95% CI, 63-95). Ambulatory ISC is accessible and feasible in an oligocentric study. PBSC allow repeated delivery of high-dose chemotherapy cycles, and result in encouraging CR, EFS, and DFS rates for poor-risk aggressive NHL's patients. [References: 29] <15> UI - 1999183802 AU - Hsu C-L AU - Shih L-Y AU - Leu H-S AU - Wu C-L AU - Funke G IN - Dr. L.-Y. Shih, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, 199 Tung-Hwa North Road, Taipei; Taiwan. TI - Septicemia due to Arthtrobacter species in a neutropenic patient with acute lymphoblastic leukemia. SO - Clinical Infectious Diseases Vol 27(5) (pp 1334-1335), 1998. <16> UI - 1999176673 AU - Russell JL AU - Block JE IN - Dr. J.L. Russell, Osteotech Inc, 51 James Way, Eatontown, NJ 07724; United States. TI - Clinical utility of demineralized bone matrix for osseous defects, arthrodesis, and reconstruction: Impact of processing techniques and study methodology. SO - Orthopedics Vol 22(5) (pp 524-531), 1999. AB - The findings of studies on DBM in the surgical management of osseous defects, arthrodeses, and reconstructive procedures have been promising. In general, DBM grafts have supported healing in a timely fashion without complication and with a diminished need to harvest bone from a secondary operative site. Nonetheless, controlled prospective trials are needed to confirm the comparative effectiveness of DBM and to quantitate the benefits of avoiding secondary site autologous bone harvesting. Notwithstanding the known deleterious effects of certain processing steps, current commercial demineralization processes vary widely and use ancillary procedures aimed at attenuating potential residual antigens and pathogens. While some of these procedures may improve or facilitate graft performance (eg, lipid and lipoprotein removal with detergents), others may be deleterious (eg, sterilization with radiation or ethylene oxide) (Table 1). Therefore, it is important that DBM be processed using methods that consistently establish conditions known to preserve DBM's documented osteoinductive potential and that authors appropriately identify processing methods known to have effects on graft performance. [References: 79] <17> UI - 1999104279 AU - Bergstrom SK AU - Gillan E AU - Quinn JJ AU - Altman AJ IN - Dr. S.K. Bergstrom, Connecticut Children's Medical Ctr., Div. of Pediat. Hematology Oncology, 282 Washington Street, Hartford, CT 06106; United States. TI - Arsenic trioxide in the treatment of a patient with multiply recurrent, ATRA-resistant promyelocytic leukemia: A case report. SO - Journal of Pediatric Hematology Oncology Vol 20(6) (pp 545-547), 1998. AB - Purpose: Little experience exists with the use of arsenic trioxide in the treatment of recurrent, all-trans retinoic acid (ATRA)-resistant, acute promyelocytic leukemia (APL). The authors report a patient with multiply recurrent APL treated with arsenic trioxide (As2O3), which was administered as recommended in the protocol from the People's Republic of China. The results of this treatment and its toxicity are discussed. The available literature on arsenic therapy is reviewed. Patients and Methods: The patient was a 15-year-old African-American girl with APL that had resisted conventional chemotherapy, ATRA therapy followed by autologous peripheral stem cell transplant, and a second course of ATRA induction therapy administered for relapse after transplant. The patient was treated with 10 mg As2O3 intravenously for 28 days. After a 4-week break, she received a second 28-day course of As2O3 therapy. Results: After completion of the first 28-day course of As2O3 treatment, morphologic and cytogenetic remission occurred. Reverse-transcription polymerase chain reaction demonstrated persistence of the PML-RARalpha fusion transcript. After the second course of As2O3, the patient had a complete remission by morphologic, cytogenetic, and molecular criteria. Approximately 6 months after the end of two courses of As2O3 therapy, the patient again underwent relapse. An additional course of As2O3 achieved a morphologic, although not a cytogenetic or molecular, remission. Conclusions: As2O3 therapy produced remission in a patient with multiply relapsed, ATRA-resistant APL. Toxic side effects were minimal. The patient underwent relapse 6 months after this therapy. Further investigation will be necessary to determine the proper role of As2O3 therapy in patients with APL. [References: 15] <18> UI - 1999063175 AU - Okada H AU - Murakami S IN - H. Okada, Dept. Periodontology/Endodontology, Osaka Univ. Faculty of Dentistry, 1-8 Yamadaoka, Osaka 565; Japan. TI - Cytokine expression in periodontal health and disease. SO - Critical Reviews in Oral Biology & Medicine Vol 9(3) (pp 248-266), 1998. AB - Soluble proteins that serve as mediators of cell function and are produced by various cell types, such as structural and inflammatory cells, are collectively called cytokines. Several lines of evidence have revealed that cytokines play important roles not only in tissue homeostasis but also in the pathogenesis of many infectious diseases. Recent research on biological activities in normal periodontium and the pathogenesis of periodontal diseases has clarified the involvement of various cytokines in the biological activities observed in the sites. Cytokines play crucial roles in the maintenance of tissue homeostasis a process which requires a delicate balance between anabolic and catabolic activities. In particular, growth factors - such as fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF), transforming growth factor- beta (TGF-beta)-are thought to play important roles in modulating the proliferation and/or migration of structural cells in the periodontium and the production of various extracellular matrices by these cells. On the other hand, there is little doubt that excessive and/or continuous production of cytokines in inflamed periodontal tissues is responsible for the progress of periodontitis and periodontal tissue destruction. Particularly, inflammatory cytokines-such as IL-1alpha, IL-1beta, IL-6, and IL-8-are present in the diseased periodontal tissues, and their unrestricted production seems to play a role in chronic leukocyte recruitment and tissue destruction. It is possible that monitoring cytokine production or its profile may allow us to diagnose an individual's periodontal disease status and/or susceptibility to the disease. In addition although the hypothesis is still controversial, it has been suggested that discrete T-cell subsets (Th1 and Th2) with different cytokine profiles play specific roles in the immunopathogenesis of periodontal diseases. [References: 171] <19> UI - 1999039442 AU - Frias AE Jr AU - Li H AU - Keeney GL AU - Podratz KC AU - Woodruff TK IN - Dr. T.K. Woodruff, Northwestern University, Dept. of Neurobiology and Physiology, 2153 N. Campus Drive, Evanston, IL 60208; United States. TI - Preoperative serum level of inhibin a is an independent prognostic factor for the survival of postmenopausal women with epithelial ovarian carcinoma. SO - Cancer Vol 85(2) (pp 465-471), 1999. AB - BACKGROUND. The aim of this study was to determine the prognostic significance of preoperative serum inhibin and activin levels in postmenopausal women with epithelial ovarian carcinoma (EOC) by correlating serum levels with disease parameters, including tumor stage and grade and patient age. METHODS. Serum levels of inhibin A, inhibin B, pro-alpha C, activin A, and activin B were quantitated with sensitive and specific two- site enzyme-linked immunosorbent assays (ELISAs) in samples collected from 44 postmenopausal women diagnosed with EOC. Serum was obtained within 14 days prior to primary tumor reductive surgery and stored at -55 [degree] C. All patients underwent definitive surgical staging and cytoreduction at Mayo Clinic and were followed for at least 5 years or until death. Postoperative adjuvant therapy was selected based on stage of disease. Demographics included 5 Stage I, 2 Stage II, 33 Stage III, and 4 Stage IV tumors, and the predominant histology was serous subtype and poorly differentiated grade. RESULTS. Inhibin A was detected in 98% of the serum samples (range, 0-12.18 pg/mL). Univariate analysis was used to demonstrate an association between patients with serum inhibin A levels exceeding the median (1.21 pg/mL) and compromised disease free (P = 0.025) and overall (P = 0.006) survival. While the 5 year disease free survival (DFS) for the entire population was 32%, the corresponding DFS rates for patients with inhibin A levels above and below the median were 100% and 43%, respectively. Similarly, the 5-year overall survival (OS) for the entire population was 35%, compared with 16% for patients above and 47% for patients below the median inhibin A level. Stepwise regression analysis that incorporated age, stage, grade, and inhibin A levels identified serum inhibin A levels above the median to be the most cogent predictor of DFS and OS. CONCLUSIONS. Preoperative serum inhibin A levels provided valuable prognostic information independent of age, stage, and grade in a postmenopausal cohort given standardized treatment for EOC. [References: 33] <20> UI - 1999016187 AU - Blaise D AU - Jourdan E AU - Michallet M AU - Jouet JP AU - Boiron JM AU - Michel G AU - Faucher C AU - Fegueux N AU - Schuller MP AU - Badri N AU - Chabannon C AU - Maraninchi D IN - Dr. D. Blaise, Transplant and Cellular Therapy Unit, Institut Paoli Calmettes, 232 Boulevard Sainte Marguerite, 13273, Marseille; France. TI - Mobilisation of healthy donors with lenograstim and transplantation of HLA-genoidentical blood progenitors in 54 patients with hematological malignancies: A pilot study. SO - Bone Marrow Transplantation Vol 22(12) (pp 1153-1158), 1998. AB - Blood cell transplantation (BCT) is now common practice in the autologous setting. We performed a pilot study of allogeneic BCT, collected after the priming of an HLA-identical sibling with a glycosylated rhu-G-CSF (lenograstim) (10 mug/kg). Fifty-four patients were included (38 +/- 11; M/F = 33/21; CML (n = 17), AML (n = 14), ALL (n = 15); MDS (n = 8)). Transplant procedures were standard (TBI regimen = 47 (87%); MTX-CsA; n = 37; CsA-PDN: n = 17). No serious adverse events were reported in donors. A median of 11 (3.5-29.1) x 106/kg CD34+ cells, 332 (33-820) x 106/kg CD3+ cells were collected. Four patients did not engraft (early death: n = 2; graft failure: n = 2). Fifty-one patients initially recovered 0.5 x 109/l ANC and 25 x 109/l platelets at 15 (10-30) and 13 (9-188) days. 29/51 and 29/38 experienced grade >= 2 acute and chronic GVHD. With a median follow-up of 25 months (18-36), relapse rate is 16% +/- 8, survival and DFS probabilities are similar (50% +/- 13). A better outcome is documented for patients under 45 years and in the early phase of the disease (n = 28), with an identical survival and DFS of 71% +/- 13. In conclusion, lenograstim is a potent rhu-G-CSF for mobilisation of allogeneic hematopoietic progenitors. Two-year follow-up indicates good haematological recovery but some concerns about graft failure and chronic GVHD have arisen deserving prospective evaluation. [References: 34] <21> UI - 1999016186 AU - Vigorito AC AU - Azevedo WM AU - Marques JFC AU - Azevedo AM AU - Eid KAB AU - Aranha FJP AU - Lorand-Metze I AU - Oliveira GB AU - Correa MEP AU - Reis ARC AU - Miranda ECM AU - De Souza CA IN - C.A. De Souza, Hemocentro-Unicamp, PO Box 6198, Barao Geraldo 13081-970 Campinas, SP; Brazil. TI - A randomised, prospective comparison of allogeneic bone marrow and peripheral blood progenitor cell transplantation in the treatment of haematological malignancies. SO - Bone Marrow Transplantation Vol 22(12) (pp 1145-1151), 1998. AB - We present the results of a prospective, randomised study comparing PBPC and BM focusing on engraftment, acute and chronic GVKD and survival. Forty patients with haematological malignancies received HLA-identical sibling BM (group A) or PBPC (group B). Evaluable patients were 19 (A) and 18 (B). Median age was 35 (17-56) in A and 29.5 (9-51) in B. Conditioning was mainly Bu-Cy2; GVHD prophylaxis was CSA-MTX. PBPC were harvested after 5 days of G-CSF 10 mug/kg/day. Median days for an ANC > 0.5 x 109/l was 18 (13-30) in A and 16 (11-25) in B (P = 0.10). Platelets > 20 x 109/l occurred at +17 (10-40) in A and +12 (9-36) in B (P = 0.01). The probability of >= 2 grade a-GVHD was 19% (A) and 27% (B) (P = 0.53). The probability of all grade c-GVHD was 70% with BM. In spite of the small number of patients in group B (PBPC), our data suggest the great majority of them will have c-GVHD (P = 0.08); extensive disease was present in 50 and 100%, respectively (P = 0.05). The estimates of overall survival for A and B at 1000 days are 51 and 47%, respectively (P = 0.67); DFS at 1000 days are 52 and 58%, respectively (P = 0.50). PBPC resulted in faster platelet engraftment. The incidence of acute and chronic GVHD was similar in both groups, but the severity of c-GVHD was higher with PBPC. No differences in survival and DFS have been observed to date. [References: 33] <22> UI - 1998379367 AU - Li H AU - Bartold PM AU - Zhang CZ AU - Clarkson RW AU - Young WG AU - Waters MJ IN - Prof. M.J. Waters, Dept. of Physiology and Pharmacology, University of Queensland, St. Lucia, QLD 4072; Australia. E-Mail: m.waters@mailbox.uq.edu.au. TI - Growth hormone and insulin-like growth factor I induce bone morphogenetic proteins 2 and 4: A mediator role in bone and tooth formation?. SO - Endocrinology Vol 139(9) (pp 3855-3862), 1998. AB - GH is known to increase the formation of bone and hard tissues of the tooth (dentine, cementum, and enamel), as do bone morphogenetic proteins. GH receptors are expressed in these tissues and could mediate local growth responses. Here we report that both GH and insulin-like growth factor I (IGF- I) are able to increase expression of bone morphogenetic protein-2 and -4 messenger RNAs 4- to 5-fold in human dental pulp fibroblasts in vitro. Induction was seen at physiological concentrations of hormone (25-100 ng/ml GH; 50-200 ng/ml IGF-I) and reached a maximum at 4-8 h. Immunoblot analysis demonstrated that the increase in messenger RNAs resulted in an increase in expressed protein. Anti-IGF-I inhibition experiments indicate that GH is able to induce the response without a requirement for local IGF-I production. These results raise the possibility that bone morphogenetic proteins mediate the local osteogenic actions of GH and IGF-I, and lend support to the view that GH can act through the mediation of factors other than IGF-I. These factors may combine with IGF-I in different tissues to enhance GH action and specificity. [References: 52] <23> UI - 1998414010 AU - Gaiger A AU - Schmid D AU - Heinze C AU - Linnerth B AU - Greinix H AU - Kalhs P AU - Tisljar K AU - Priglinger S AU - Laczika K AU - Mitterbauer M AU - Novak M AU - Mitterbauer G AU - Mannhalter C AU - Haas OA AU - Lechner K AU - Jager U IN - A. Gaiger, First Dept of Medicine, Division of Hematology, University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna; Austria. TI - Detection of the WT1 transcript by RT-PCR in complete remission has no prognostic relevance in de novo acute myeloid leukemia. SO - Leukemia Vol 12(12) (pp 1886-1894), 1998. AB - The WT1 gene is expressed in 73-100% of patients with acute myelogenous leukemia (AML) and is thought to play a role in maintaining the viability of leukemic cells. WT1 has been proposed as a marker for minimal residual disease in leukemia. We obtained serial blood or bone marrow samples from patients with de novo AML at diagnosis, during therapy, and up to 95 months after diagnosis and analyzed for WT1 gene expression by RT-PCR to determine whether gene expression was predictive of relapse. Forty-four patients had WT1-positive AML and achieved a complete remission (CR) following chemotherapy and 24 patients underwent unrelated donor (n = 4), sibling donor (n = 13) or autologous (n = 7) marrow transplantation. After achieving CR 62% of the patients became WT1-negative, while 38% remained WT1-positive. There was no difference in the disease-free survival (DFS) and survival from remission between WT1-positive and -negative patients (P > 0.1). Following BMT, 32% of the patients analyzed in CR within the first 100 days after transplantation were WT1 PCR positive. Detection of WT1 transcripts within 100 days following BMT did not affect DFS and overall survival (OS) after transplantation (P > 0.1). Ten of 11 patients who are in continuous CR following chemotherapy or BMT for more than 3 years were transiently WT1-positive during the observation period. Four of these patients displayed the WT1 transcript at the last examination. Thirteen of 39 patients were WT1 PCR negative within 4 months before clinical onset of relapse and eight patients were WT1 PCR negative at time of relapse. These data indicate that: (1) achievement of WT1 negativity is not associated with longer DFS, survival from remission, or OS after transplantation; (2) not all patients who relapse become WT1 positive again; (3) long-term remitters frequently display the WT1 transcript. Thus, we conclude that the monitoring of WT1 gene expression by qualitative RT-PCR during treatment and CR is of very limited value. [References: 44] <24> UI - 1998405180 AU - Plenk H Jr IN - Dr. H. Plenk Jr., Dept. for Bone and Biomaterials Res., Histological-Embryological Institute, University of Vienna, Vienna; Austria. E-Mail: Hanns.Plenk@univie.2c.2t. TI - Prosthesis-bone interface. SO - Journal of Biomedical Materials Research Vol 43(4) (pp 350-355), 1998. AB - In this overview, which is based on selected books and reviews, the microscopic appearances of prosthesis-bone interfaces resulting from clinically relevant implantation techniques are highlighted. The following techniques are distinguished to insert and attach prostheses in the recipient bone: impaction into bone, primary mechanical interlocking, cement fixation, bone ongrowth and secondary mechanical interlocking with bioinert materials, and enhanced bone ongrowth and bone bonding to bioactive materials. The resulting typical histomorphologies of orthopedic and dental prostheses-bone interfaces are described and illustrated from the author's studies employing light, fluorescence, and backscattered electron microscopy, and corresponding microradiographs of undecalcified ground sections of bone and implants. Special emphasis is given to the mineralization-demineralization kinetics of the interfacial bone matrix interacting with specific surface reactions of some implant materials. Consequently, the distinction between bioinert and bioactive prosthetic materials is critically analyzed. [References: 38] <25> UI - 1998381597 AU - Del Pozo MA AU - Anton F AU - Arias JR AU - Carro JA AU - Pinilla J AU - Perez MR AU - Labarga P AU - Echevarria S AU - Alcoba M AU - Garrote E AU - De la Cruz FJM AU - Moreno-Otero R IN - Dr. M.A. Del Pozo, Unidad de Enfermedades Infecciosas, Hospital Clinico Universitario, C- Ramon y Cajal s-n, 47011 Valladolid; Spain. TI - Interferon alpha treatment of chronic hepatitis C in HIV-infected patients receiving zidovudine: Efficacy, tolerance and response related factors. SO - Hepato-Gastroenterology Vol 45(23) (pp 1695-1701), 1998. AB - BACKGROUND/AIMS: In our area most of the human immunodeficiency virus (HIV) infected patients are intravenous drug users; HIV and hepatitis C virus infections often coexist in these patients. Due to the repercussions of both infections, we designed atrial to evaluate the efficacy, response-related factors and tolerance during an eight-month regime of recombinant interferon alpha-2b on hepatitis C virus infection. METHODOLOGY: We included 79 patients in an open, prospective and multicentric trial with zidovudine and interferon alpha-2b. Response to interferon treatment was evaluated by biochemical and histopathological criteria. RESULTS: A complete response (alanine aminotransferase normalization) was obtained in 57.4% of patients. The significant response-related factors were: degree of histopathological activity, CD4+ cell number and initial leukocyte number. CONCLUSIONS: Recombinant interferon therapy seems to be effective for chronic hepatitis C in HIV infected patients; the best response was in those with active chronic hepatitis and CD4+ cell counts >= 200/mm3. General tolerance was variable, although side effects were not different from those seen in non-HIV patients. The most common side effect was flu-like syndrome (constitutional manifestations), with no interference on treatment continuity; however, hematological toxicity prevents the indiscriminate use of interferon. [References: 25] <26> UI - 1998303525 AU - Jensen B AU - Schroder U IN - B. Jensen, Department of Pedodontics, Faculty of Odontology, Lund University, Carl Gustavs vag 34, S-214 21 Malmo; Sweden. TI - Acceptance of dental care following early extractions under rectal sedation with diazepam in preschool children. SO - Acta Odontologica Scandinavica Vol 56(4) (pp 229-232), 1998. AB - The aim of the study was to evaluate the effect of amnesia in preschool children on their later acceptance of dental care. Forty-six 4-6-year-old children, who between 2 and 4 years previously had had primary incisors extracted because of trauma, were reexamined for dental health and acceptance of dental care. The extractions had been performed under rectal sedation with diazepam (0.7 mg/kg body weight). Information about dental treatment and degree of cooperation during the intervening period was obtained from records at the referring clinic. The parents were interviewed about their child's experience of amnesia concerning the extractions, background variables, and experiences of dental care before the follow-up examination. Amnesia concerning the extractions was reported in 85% of the children. Twenty-nine percent had on some occasion exhibited behavior management problems (BMP) during the intervening period. Lack of amnesia was significantly associated with BMP (P < 0.002). Children without amnesia concerning the extractions tended to accept dental are less well at the reexamination. Parents were able to predict their child's acceptance of dental care at the follow-up with a significant degree of success (P = 0.02). In conclusion, amnesia in preschool children concerning extractions seems to be essential to facilitate positive acceptance of future dental care. [References: 21] <27> UI - 1998300660 AU - Southard GL AU - Dunn RL AU - Garrett S IN - G.L. Southard, Atrix Laboratories, Inc., Fort Collins, CO; United States. TI - The drug delivery and biomaterial attributes of the ATRIGEL(TM) technology in the treatment of periodontal disease. SO - Expert Opinion on Investigational Drugs Vol 7(9) (pp 1483-1491), 1998. AB - Two new products, ATRIDOX(TM) Periodontal Treatment and ATRISORB(TM) Guided Tissue Regeneration (GTR) Barrier have been evaluated as therapies for periodontal disease. Both products are based on the unique ATRIGEL(TM) technology. The system consists of a solution of a resorbable polymer in a biocompatible carrier. On in vivo administration, the polymer undergoes a phase change from a liquid to an in situ formed implant. Being in liquid form, it initially provides the advantage of in vivo placement by simple means, such as syringes to form implants at the site of use. The system is biocompatible and has the capability of serving as a biomaterial and a drug delivery system. The bioabsorption rates of various, polymers and the release rates for a wide variety of drugs ranging from simple organics to proteins and peptides are tailored to the desired indication. Release periods ranging from one week to four months have been achieved with one month being the most often desired. For these reasons the ATRIGEL(TM) system is being applied to a number of medical applications ranging from site and systemic oncology to post-operative pain control and bone regeneration using growth factors. However, its most visible application to date has been in the development of a pipeline of products for the treatment of periodontal disease, which is the focus of this paper. [References: 37] <28> UI - 1998296769 AU - Fowler MJ Jr AU - Neff MS AU - Borghaei RC AU - Pease EA AU - Mochan E AU - Thornton RD IN - R.D. Thornton, Dept. Biochemistry-Molecular Biology, Philadelphia Col. Osteopathic Med., Evans Hall, 4170 City Ave, Philadelphia, PA 19131; United States. TI - Induction of bone morphogenetic protein-2 by interleukin-1 in human fibroblasts. SO - Biochemical & Biophysical Research Communications 30 JUL 1998Vol 248(3) (pp 450-453), 1998. AB - Rheumatoid arthritis and periodontitis are chronic inflammatory diseases associated with tissue destruction that is mediated in part by elevated levels of cytokines (e.g. interleukin-1 and tumor necrosis factor). Differential screening of a human synovial fibroblast cDNA library for interleukin-1 induced genes revealed a clone identical to the gene encoding human bone morphogenetic protein-2. Northern blot analysis of human synovial fibroblast mRNA confirmed up-regulation of bone morphogenetic protein-2 in the presence of interleukin-1. Utilizing a specific antibody, levels of bone morphogenetic protein-2 protein in conditioned medium from synovial fibroblasts were also up-regulated in the presence of interleukin-1. This is the first report of the production of bone morphogenetic protein-2 by synovial fibroblasts, and the first report of its up-regulation in response to interleukin-1. However, interleukin-1 did not induce bone morphogenetic protein-2 mRNA in human gingival fibroblasts. [References: 22] <29> UI - 1998292926 AU - Vanrenterghem Y IN - Dr. Y. Vanrenterghem, Department of Nephrology, University Hospital Gasthuisberg, Herestraat 49, B3000 Leuven; Belgium. TI - Tacrolimus (FK 506) in kidney transplantation. SO - Transplantation Proceedings Vol 30(5) (pp 2171-2173), 1998. <30> UI - 1998239661 AU - Tomas JF AU - Lopez-Lorenzo JL AU - Requena MJ AU - Aguilar R AU - Steegmann JL AU - Camara R AU - Alegre A AU - Arranz R AU - Figuera A AU - Fernandez-Ranada JM IN - Dr. J.F. Tomas, Servicio de Hematologia, Hospital Universitario La Princesa, Diego de Leon 62, 28006-Madrid; Spain. TI - Absence of influence of prior treatment with interferon on the outcome of allogeneic bone marrow transplantation for chronic myeloid leukemia. SO - Bone Marrow Transplantation Vol 22(1) (pp 47-51), 1998. AB - Timing of transplantation in the chronic phase of chronic myeloid leukemia (CML) and previous treatment with interferon remains controversial. We have tried to discover what influence pretreatment with interferon alpha (IFN-A) has on the results of allogeneic bone marrow transplantation for CML patients treated in a single institution. Fifty-one consecutive patients with chronic phase Ph-positive CML who received an allogeneic bone marrow transplantation from a HLA-identical familial donor were evaluated. Thirty had been treated with IFN-A (IFN+ group) prior to BMT and twenty-one had not (IFN- group). Both groups were homogeneous for clinical characteristics such as age, sex, previous chemotherapy, disease status, and time from diagnosis to transplant. No difference was found in neutrophil and platelet count recovery between the IFN+ and IFN- group. The incidence of acute and chronic GVHD, VOD and severe mucositis was not significantly different. Relapse and both overall survival and DFS were similar for both groups. No adverse effects of prior IFN exposure on the outcome of HLA-identical sibling donor BMT for chronic phase CML patients were found in this study. [References: 27] <31> UI - 1998173045 AU - Ma JK-C AU - Hikmat BY AU - Wycoff K AU - Vine ND AU - Chargelegue D AU - Yu L AU - Hein MB AU - Lehner T IN - J.K.-C. Ma, Department of Immunology, United Medical and Dental Schools, Guy's Hospital, London Bridge, London SE1 9RT; United Kingdom. E-Mail: j.ma@umds.ac.uk. TI - Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans. SO - Nature Medicine Vol 4(5) (pp 601-606), 1998. AB - A functional comparison was made between a monoclonal secretory antibody generated in transgenic plants and its parent murine IgG antibody. The affinity constants of both antibodies for a Streptococcus mutans adhesion protein were similar. However the secretory antibody had a higher functional affinity due to its dimeric structure. In the human oral cavity, the secretory antibody survived for up to three days, compared with one day for the IgG antibody. The plant secretory antibody afforded specific protection in humans against oral streptococcal colonization for at least four months. We demonstrate that transgenic plants can be used to produce high affinity, monoclonal secretory antibodies that can prevent specific microbial colonization in humans. These findings could be extended to the immunotherapeutic prevention of other mucosal infections in humans and animals. [References: 20] <32> UI - 1998166415 AU - Witz F AU - Sadoun A AU - Perrin M-C AU - Berthou C AU - Briere J AU - Cahn J-Y AU - Lioure B AU - Witz B AU - Francois S AU - Desablens B AU - Pignon B AU - Le Prise P-Y AU - Audhuy B AU - Caillot D AU - Casassus P AU - Delain M AU - Christian B AU - Tellier Z AU - Polin V AU - Hurteloup P AU - Harousseau J-L IN - Dr. F. Witz, Service de Medecine A, Hopital de Brabois, CHU de Nancy, Rue du Morvan, 54511 Vandoeuvre Cedex; France. TI - A placebo-controlled study of recombinant human granulocyte-macrophage colony-stimulating factor administered during and after induction treatment for de novo acute myelogenous leukemia in elderly patients. SO - Blood 15 APR 1998Vol 91(8) (pp 2722-2730), 1998. AB - The complete remission (CR) rate after intensive chemotherapy for acute myelogenous leukemia (AML) remains low in elderly patients, mainly because of a higher infectious mortality rate related to neutropenia and an increased incidence of adverse prognostic factors. Granulocyte-macrophage colony- stimulating factor (GM-CSF) has been shown to potentially recruit leukemic blasts into cell cycle and improve cytotoxic effects when given during chemotherapy, and to shorten the duration of neutropenia when administered after chemotherapy. Two hundred forty patients aged 55 to 75 years who had newly diagnosed AML were randomly assigned to receive placebo or Escherichia coli-derived GM-CSF (5 mug/kg/d by 6-hour intravenous infusion) starting during induction chemotherapy on day 1 and continued through and after chemotherapy until recovery of neutrophils, or evidence of regrowth of leukemia or up to day 28. Induction chemotherapy consisted of idarubicin (8 mg/m2/d on days 1 to 5) and cytarabine (100 mg/m2/d on days 1 to 7). The study drug was not administered subsequent to the induction course. Patients who achieved a CR received continuous maintenance therapy for 1 year with four quarterly reinduction courses; in the 55- to 64-year age subgroup, patients were randomly assigned to receive or not a consolidation course before maintenance therapy. The CR rate was similar in the GM-CSF and placebo groups (63% and 60.5%, respectively; P = .79). The mortality, rate of resistant disease, and rate of regrowth of leukemia were also similar in both groups. The time to neutrophil recovery was shorter in patients who received GM-CSF (24 v 29 days; P = .0001), but the incidence and characteristics of infectious events were not different. The 2-year disease-free survival (DFS) rate was significantly improved in the GM-CSF group (48% v 21% in the placebo group, P = .003). This effect was highly significant in the cohort of patients aged 55 to 64, but only marginal in patients <= 65 years of age. There was a trend toward a longer overall survival (OS) in the GM-CSF group (P = .082). In summary, the administration of GM-CSF, concomitantly with chemotherapy and thereafter during induction course in AML, shortened the time to neutrophil recovery, but did not improve the CR rate in patients aged 55 to 75. Nonetheless, DFS and OS were significantly prolonged in patients aged 55 to 64 treated with GM-CSF. These results are promising and further evaluation of myeloid growth factors in AML is warranted. [References: 45] <33> UI - 1998144000 AU - Wright LE AU - Schwarcz HP IN - L.E. Wright, Department of Anthropology, Texas A and M University, College Station, TX 77843-4352; United States. E-Mail: lwright@tamu.edu. TI - Stable carbon and oxygen isotopes in human tooth enamel: Identifying breastfeeding and weaning in prehistory. SO - American Journal of Physical Anthropology Vol 106(1) (pp 1-18), 1998. AB - This paper investigates the utility of stable carbon and oxygen isotopes in human dental enamel to reveal patterns of breastfeeding and weaning in prehistory. Enamel preserves a record of childhood diet that can be studied in adult skeletons. Comparing different teeth, we used delta13C to document the introduction of solid foods to infant diets and delta18O to monitor the decline of breastfeeding. We report enamel carbonate delta13C and delta18O of 33 first molars, 35 premolars, and 25 third molars from 35 burials from Kaminaljuyu, an early state in the valley of Guatemala. The skeletons span from Middle Preclassic through Late Postclassic occupations, ca. 700 B.C. to 1500 A.D. Sections of enamel were removed from each tooth spanning from the cusp to the cemento-enamel junction. Stable isotope ratios were measured on CO2 liberated by reaction of enamel with H3PO4 in an automated carbonate system attached to a VG Optima mass spectrometer. Within a skeleton, teeth developing at older ages are more enriched in 13C and more depleted in 18O than teeth developing at younger ages. Premolars average 0.5% higher in delta13C than first molars from the same skeleton (P = 0.0001), but third molars are not significantly enriched over premolars. The shift from first molars to premolars may be due to the shift to solid foods from lipid-rich milk. After 2 years, when premolars begin to mineralize, the delta13C in childhood diets did not change systematically. First molars and premolars are similar in delta18O, but third molars average 0.7% lower than first molars (P = 0.0001) and 0.5% lower than premolars (P = 0.0003). First molar and premolar delta18O is heavier, because breast milk is more enriched in 18O than is drinking water. Hence, many children continued to nurse during the period of premolar formation. Together, these results indicate that Kaminaljuyu children had begun to eat solid maize foods before the age of 2 years but continued to drink breast milk until much later. [References: 84] <34> UI - 1998114996 AU - Lukash FN AU - Schwartz M AU - Grauer S AU - Tuminelli F AU - Brown AS AU - Millard DR AU - Hall CD IN - Dr. F.N. Lukash, 1129 Northern Boulevard, Manhasset, NY 11030; United States. TI - Dynamic cleft maxillary orthopedics and periosteoplasty: Benefit or detriment?. SO - Annals of Plastic Surgery Vol 40(4) (pp 321-327), 1998. AB - In 1990, Drs Millard and Latham published their initial experience with dynamic maxillary appliances (DMAs) and periosteoplasty for children with cleft lip and palate. The technique provided for alveolar alignment and consolidation, with elimination of oronasal fistulas. Opponents to this approach speculated about impairments to facial growth. To date no longitudinal studies have been published. Over the last 10 years, 35 unilateral and 10 bilateral complete clefts have been treated with this technique. All patients have been followed and documented clinically, orthodontically, an radiographically. Cephalometric analyses were performed on children after the age of 6 years. The children have excellent facial aesthetics with well-balanced lips and noses. Radiographs demonstrate bone within the repaired alveolar clefts. Articulated impressions show anterior and lateral crossbites in the unilateral patients that improve over time and appear to be correctable orthodontically. The bilateral patients have satisfactory occlusions and arch forms. Cephalometric analyses confirmed no evidence of skeletal crossbites or midfacial growth retardation. This is a work in progress that will continue as the children grow. Although definite and final conclusions would be premature, it can be stated that to date all patients are following consistent and favorable growth patterns. Our team is confident in proceeding with this technique. [References: 9] <35> UI - 1998085904 AU - Reddi AH IN - A.H. Reddi, Ctr. for Tissue Regeneration/Repair, Department of Orthopedic Surgery, University of California, Sacramento, CA 95817; United States. E-Mail: ahreddi@ucdavis.edu. TI - Role of morphogenetic proteins in skeletal tissue engineering and regeneration. SO - Nature Biotechnology Vol 16(3) (pp 247-252), 1998. AB - Morphogenesis is the developmental cascade of pattern formation and body plan establishment, culminating in the adult form. It has formed the basis for the emerging discipline of tissue engineering, which uses principles of molecular developmental biology and morphogenesis gleamed through studies on inductive signals, responding stem cells, and the extracellular matrix to design end construct spare parts that restore function to the human body. Among the many organs in the body, bone has considerable powers for regeneration and is prototype model for tissue engineering. Implantation of demineralized bone matrix into subcutaneous sites results in local bone induction. This model mimics sequential limb morphogenesis and has permitted the isolation of bone morphogens, such as bone morphogenetic proteins (BMPs), from demineralized adult bone matrix. BMPs initiate, promote, and maintain chondrogenesis and osteogenesis, but are also involved in the morphogenesis of organs other than bone. The symbiosis of the mechanisms underlying bone induction and differentiation is critical for tissue engineering and is governed by both biomechanics (physical forces) and context (microenvironment/extracellular matrix), which can be duplicated by biomimetic biomaterials such as collagens, hydroxyapatite, proteoglycans, and cell adhesion glycoproteins, including fibronectins and laminin. Rules of tissue architecture elucidated in bone morphogenesis may provide insights into tissue engineering and be universally applicable for all organs/tissues, including bones and joints. [References: 66] <36> UI - 1998043186 AU - Block JE AU - Russell JL AU - Helm GA AU - Sheehan J TI - Spine fusion with demineralized bone [3]. SO - Journal of Neurosurgery Vol 88(2) (pp 354-355), 1998. <37> UI - 1998028275 AU - Howell TH AU - Fiorellini JP AU - Paquette DW AU - Offenbacher S AU - Giannobile WV AU - Lynch SE IN - Dr. T.H. Howell, Department of Periodontology, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115-5888; United States. TI - A phase I/II clinical trial to evaluate a combination of recombinant human platelet-derived growth factor-BB and recombinant human insulin-like growth factor-I in patients with periodontal disease. SO - Journal of Periodontology Vol 68(12) (pp 1186-1193), 1997. AB - THE PRIMARY OBJECTIVE OF THIS STUDY was to assess the safety of recombinant human (rh) platelet-derived growth factor-BB (PDGF-BB) and (rh) insulin-like growth factor-I (IGF-I) when applied to periodontal osseous defects in humans; a secondary objective was to begin to accrue data on the therapeutic dose of these growth factors (GFs) required to stimulate periodontal regeneration. Thirty-eight human subjects possessing bilateral osseous periodontal lesions were assigned to one of two treatment groups in a split-mouth design. Following full-thickness flap reflection, test sites received local application of the therapeutic drug delivered in coded syringes by a 'masked' investigator. Two dose levels were tested, 50 mug/ml each of rhPDGF-BB and rhIGF-I in a gel vehicle (LD-PDGF/IGF-I) and 150 mug/ml each of rhPDGF-BB and rhIGF-I plus vehicle (HD-PDGF/IGF-I). Control treatment consisted of either conventional periodontal flap surgery or surgery plus vehicle. Safety analyses included physical examination, hematology, serum chemistry, urinalysis, antibody titers, and radiographic evaluation of bony changes. The primary therapeutic assessment was bone fill measured at re- entry 6 to 9 months after treatment. No local or systemic safety issues were found as a result of GF administration. No patients developed antibodies to the rhGF proteins. In subjects treated with LD-PDGF/IGF-I, there were no enhancements in periodontal regeneration compared to controls. However, in patients treated with HD-PDGF/IGF-I, statistically significant increases in alveolar bone formation were noted as measured by surgical re-entry 9 months following drag delivery (P < 0.05). This corresponded to an increase of 2.08 mm of new vertical bone height and 42.3% osseous defect fill in the HD- PDGF/IGF-I subjects versus only 0.75 mm and 18.5% gains in new bone height and osseous fill, respectively, in the controls. Furcation lesions, although limited in number, responded most favorably to treatment, with 2.8 mm horizontal osseous fill. The results from this study suggest that the local application of rhPDGF-BB and rhIGF-I to periodontal lesions is safe at the dose levels studied. LD-PDGF/IGF-I did not elicit increased defect fill compared to the control; however, HD-PDGF/IGF-I resulted in a significant promotion in bone regeneration. Additional studies are warranted to more fully characterize the effects of PDGF/IGF-I on periodontal regeneration in humans. [References: 18] <38> UI - 1998010563 AU - Gagnon L AU - Boulet LP AU - Brown J AU - Desrosiers T IN - Dr. T. Desrosiers, Dept. des Sci. des Aliments/Nutri., FSAA, Pavillon Paul-Comtois, Sainte-Foy, Que. G1K 7P4; Canada. TI - Influence of inhaled corticosteroids and dietary intake on bone density and metabolism in patients with moderate to severe asthma. SO - Journal of the American Dietetic Association Vol 97(12) (pp 1401-1406), 1997. AB - Objectives: Compare the effect of high doses of inhaled corticosteroids on bone loss in subjects with moderate to severe asthma or mild asthma, and examine the influence of dietary intake on bone metabolism. Design: A survey on the effects of corticotherapy and nutrition on bone density was conducted in 74 subjects currently being treated for asthma in the asthma clinic of Hopital Laval (Sainte-Foy, Quebec, Canada). Fifty-eight subjects completed the study (attrition rate=15%). Main outcome measures: In all subjects expiratory volumes were determined and urinary analysis was conducted for hydroxyproline, calcium, phosphorus, and cortisol levels. Osteocalcin, calcium, phosphorus, cortisol, alkaline phosphatase, and gamma- glutamyltransferase levels were measured in blood samples. Bone density of the lumbar spine was determined by means of dual-energy x-ray absorptiometry. Nutrition evaluation was based on a 3-day food diary analyzed using progiciel Nutri 91. The nutritional parameters examined were calcium; phosphorus; magnesium; zinc; vitamins A, C, and D; protein; total fiber; oxalates; energy; caffeine; and alcohol in relation to bone density. Subjects: Thirty- one patients with moderate to severe asthma who had been taking more than 1,000 mug beclomethasone per day or the equivalent for more than 2 years and 27 patients with mild asthma who were taking less than 500 mug beclomethasone per day or the equivalent. Statistical analyses performed: Four-factor analysis of variance with hierarchized interactions of four levels, Duncan's test, Pearson correlation coefficients. Results: Blood levels of osteocalcin and protein intake were lower in patients with moderate to severe asthma than in those with mild asthma (P<.05). Significant correlations (P<.02) were observed between bone density and calcium intake (r=.40), phosphorus intake (r=.35), protein intake (r=.30), and serum alkaline phosphatase level (r=- .30). Bone density was not significantly different between the two groups of patients with asthma. Applications: A follow-up of patients with asthma who are taking inhaled corticosteroids is needed to assess bone density, osteocalcin levels, and dietary intakes of calcium. Verify if osteocalcin level decreases over time in patients with moderate to severe asthma, monitor possible modifications in bone density, and verify if the correlation between dietary calcium and bone density is maintained. [References: 35] <39> UI - 1998002189 AU - Yakisan E AU - Schirg E AU - Zeidler C AU - Bishop NJ AU - Reiter A AU - Hirt A AU - Riehm H AU - Welte K IN - Dr. K. Welte, Padiatrische Hamatologie/Onkologie, Kinderklin. Med. Hochschule Hannover, D-30625 Hannover; Germany. TI - High incidence of significant bone loss in patients with severe congenital neutropenia (Kostmann's syndrome). SO - Journal of Pediatrics Vol 131(4) (pp 592-597), 1997. AB - Objective: Clinical observation of bone pain, unusual fractures in two patients, and diffuse osteopenia/osteoporosis led us to assess bone mineral content and density in 30 patients with severe congenital neutropenia who were treated with recombinant-methionyl-human granulocyte colony-stimulating factor (r-metHuG-CSF). Study design: We reviewed roentgenograms in 29 of these 30 patients to evaluate bone loss before and during treatment. In addition, in 17 of the 30 patients, bone mineral status could be assessed by both quantitative computed tomography (Q-CT; n = 16) and dual energy x-ray absorptiometry (DXA; n = 1). In one patient, Q-CT was not possible because of severe vertebral fractures. Results: Of the 30 patients investigated, 15 had evidence of osteopenia/osteoporosis observed on spine radiographs (n = 5), on Q-CT/DXA (n = 1/n = 1), or on radiographs and Q-CT (n = 8). In 13 of the 30 patients, only a lateral radiograph of the lumbar spine was available, 5 of 13 showing either increased kyphosis and wedging of the vertebrae or compression fractures of the vertebral bodies, indicating severe established osteoporosis. In eight patients, the findings of the spinal radiographs were normal. In nine patients, spinal radiographs were taken before r-metHuG-CSF treatment. Osteoporotic vertebral deformation (n = 3) or reduced bone mass (n = 3) was seen in six of these nine patients. The levels of serum biochemical markers of bone metabolism were all within normal ranges except for mild elevation of the serum alkaline phosphatase level. The degree of spinal bone mineral loss did not correlate with dose and duration of r-metHuG-CSF treatment or with the age or sex of the patients. Conclusions: These data indicate a high incidence of bone mineral loss in children with severe congenital neutropenia. The underlying pathogenesis of bone demineralization is not clear. It is more likely that the bone loss was caused by the pathophysiologic features of the underlying disease, but it is possible that r-metHuG-CSF accelerates bone mineral loss. [References: 27] <40> UI - 1997383782 AU - Lowenberg B AU - Boogaerts MA AU - Daenen SMGJ AU - Verhoel GEG AU - Hogenbeek A AU - Vellenga E AU - Ossenkoppele GJ AU - Huijgens PC AU - Verdonck LF AU - Van der Lelie J AU - Wielenga JJ AU - Schouten HC AU - Gmur J AU - Gratwohl A AU - Hess U AU - Fey MF AU - Van Putten WLJ IN - Dr. B. Lowenberg, University Hospital Rotterdam, Daniel den Hoed Cancer Center', PO Box 5201, 3008 AE Rotterdam; Netherlands. E-Mail: lowenberg@haed.azr.nl. TI - Value of different modalities of granulocyte-macrophage colony- stimulating factor applied during or after induction therapy of acute myeloid leukemia. SO - Journal of Clinical Oncology Vol 15(12) (pp 3496-3506), 1997. AB - Purpose: The hematopoietic growth factors (HGFs) introduced into induction chemotherapy (CT) of acute myeloid leukemia (AML) might be of benefit to treatment outcome by at least two mechanisms. HGFs given on days simultaneously with CT might sensitize the leukemic cells and enhance their susceptibility to CT. HGFs applied after CT might hasten hematopoietic recovery and reduce morbidity or mortality. Materials and Methods: We set out to evaluate the use of granulocyte-macrophage colony-stimulating factor (GM- CSF; 5 mug/kg) in a prospective randomized study of factorial design (yes or no GM-CSF during CT, and yes or no GM-CSF after CT) in patients aged 15 to 60 years (mean, 42) with newly diagnosed AML. GM-CSF was applied as follows: during CT only (+/-, n = 64 assessable patients), GM-CSF during and following CT (+/+, n = 66), no GM-CSF (-/-, n = 63), or GM-CSF after CT only (-/+, n = 60). Results: The complete response (CR) rate was 77%. At a median follow-up time of 42 months, probabilities of overall survival (OS) and disease-free survival (DFS) at 3 years were 38% and 37% in all patients. CR rates, OS, and DFS did not differ between the treatment groups (intention-to-treat analysis). Neutrophil recovery (1.0 x 109/L) and monocyte recovery were significantly faster in patients who received GM-CSF after CT (26 days v 30 days; neutrophils, P < .001; monocytes, P < .005). Platelet regeneration, transfusion requirements, use of antibiotics, frequency of infections, and duration of hospitalization did not vary as a function of any of the therapeutic GM-CSF modalities. More frequent side effects (eg, fever and fluid retention) were noted in GM-CSF-treated patients predominantly related to the use of GM-CSF during CT. Conclusion: Priming of AML cells to the cytotoxic effects of CT by the use of GM-CSF during CT or accelerating myeloid recovery by the use of GM-CSF after CT does not significantly improve treatment outcome of young and middle-aged adults with newly diagnosed AML. [References: 35] <41> UI - 1997383782 AU - Lowenberg B AU - Boogaerts MA AU - Daenen SMGJ AU - Verhoel GEG AU - Hogenbeek A AU - Vellenga E AU - Ossenkoppele GJ AU - Huijgens PC AU - Verdonck LF AU - Van der Lelie J AU - Wielenga JJ AU - Schouten HC AU - Gmur J AU - Gratwohl A AU - Hess U AU - Fey MF AU - Van Putten WLJ IN - Dr. B. Lowenberg, University Hospital Rotterdam, Daniel den Hoed Cancer Center', PO Box 5201, 3008 AE Rotterdam; Netherlands. E-Mail: lowenberg@haed.azr.nl. TI - Value of different modalities of granulocyte-macrophage colony- stimulating factor applied during or after induction therapy of acute myeloid leukemia. SO - Journal of Clinical Oncology Vol 15(12) (pp 3496-3506), 1997. AB - Purpose: The hematopoietic growth factors (HGFs) introduced into induction chemotherapy (CT) of acute myeloid leukemia (AML) might be of benefit to treatment outcome by at least two mechanisms. HGFs given on days simultaneously with CT might sensitize the leukemic cells and enhance their susceptibility to CT. HGFs applied after CT might hasten hematopoietic recovery and reduce morbidity or mortality. Materials and Methods: We set out to evaluate the use of granulocyte-macrophage colony-stimulating factor (GM- CSF; 5 mug/kg) in a prospective randomized study of factorial design (yes or no GM-CSF during CT, and yes or no GM-CSF after CT) in patients aged 15 to 60 years (mean, 42) with newly diagnosed AML. GM-CSF was applied as follows: during CT only (+/-, n = 64 assessable patients), GM-CSF during and following CT (+/+, n = 66), no GM-CSF (-/-, n = 63), or GM-CSF after CT only (-/+, n = 60). Results: The complete response (CR) rate was 77%. At a median follow-up time of 42 months, probabilities of overall survival (OS) and disease-free survival (DFS) at 3 years were 38% and 37% in all patients. CR rates, OS, and DFS did not differ between the treatment groups (intention-to-treat analysis). Neutrophil recovery (1.0 x 109/L) and monocyte recovery were significantly faster in patients who received GM-CSF after CT (26 days v 30 days; neutrophils, P < .001; monocytes, P < .005). Platelet regeneration, transfusion requirements, use of antibiotics, frequency of infections, and duration of hospitalization did not vary as a function of any of the therapeutic GM-CSF modalities. More frequent side effects (eg, fever and fluid retention) were noted in GM-CSF-treated patients predominantly related to the use of GM-CSF during CT. Conclusion: Priming of AML cells to the cytotoxic effects of CT by the use of GM-CSF during CT or accelerating myeloid recovery by the use of GM-CSF after CT does not significantly improve treatment outcome of young and middle-aged adults with newly diagnosed AML. [References: 35] <42> UI - 1997311266 AU - Ochiai T AU - Isono K IN - T. Ochiai, Department of Surgery, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260; Japan. TI - Advances in the development of immunosuppressive agents in organ transplantation. SO - Surgery Today Vol 27(10) (pp 883-891), 1997. <43> UI - 1997286540 AU - Takahashi M AU - Koike T AU - Aizawa Y AU - Kashimura M AU - Hayatsu K AU - Nagai K-I AU - Abe A AU - Urushiyama M AU - Yagisawa K IN - Dr. M. Takahashi, Department of Medical Technology, School of Biomedical Technology, Niigata University, Asahimachi 2-746, Niigata 951; Japan. E-Mail: matak@clg.niigata-u.ac.jp. TI - Complete remission in three patients with acute myeloblastic leukemia by administration of G-CSF without antileukemic agents. SO - American Journal of Hematology Vol 56(1) (pp 42-44), 1997. AB - We describe 3 patients with acute myeloblastic leukemia (AML), who received rhG-CSF for infections such as pneumonia or for prophylaxis of infection, and who achieved complete remission. They had not received any antileukemic therapy before or during the administration of rhG-CSF. These findings suggest the possibility that complete remission can be brought about by G-CSF itself in some patients with AML. [References: 6] <44> UI - 1997272549 AU - Wismeijer D AU - Van Waas MAJ AU - Vermeeren JIJ AU - Kalk W IN - D. Wismeijer, Zutphensestraatweg 26, 6995 AH Ellecom; Netherlands. TI - Patients' perception of sensory disturbances of the mental nerve before and after implant surgery: A prospective study of 110 patients. SO - British Journal of Oral & Maxillofacial Surgery Vol 35(4) (pp 254-259), 1997. AB - In a randomized controlled clinical trial 110 edentulous patients with severe mandibular bone loss have been treated with ITI-dental implants using three different treatment strategies: (1) a mandibular overdenture supported by two implants with ball attachments, (2) two implants with an interconnecting bar or (3) by four interconnected implants. As implant surgery involves elevation of the mucoperiosteum, bone remodeling at the implant site and insertion of implants close to the mental foramen, altered sensations of the mental nerve caused by the surgery are to be expected. An altered sensation of the lower lip can also be caused by pressure of an ill-fitting lower denture on the mental foramen, or in the case of severe bone loss of the alveolar ridge, on the alveolar nerve itself. This article presents the results of the patients' perception of the sensation of their lower lip before, 10 days after and 16 months after implant surgery in the mandible. It shows that 25% of the patients describe a sensory disturbance before treatment. This 25% also showed high scores on the Hopkins Symptoms Check List indicating a tendency to somatize complaints. Eleven percent of the patients report a sensory disturbance in the lower lip 10 days after surgery. Ten percent report a sensory disturbance 16 months after surgery of which one third also reported a disturbance before the treatment. This implies the risk of a sensory disturbance of the lower lip to be a possible complication after implant surgery. Therefore patients must be informed about this phenomenon before treatment. [References: 18] <45> UI - 1997248307 AU - Kivitie-Kallio S AU - Rajantie J AU - Juvonen E AU - Norio R IN - Dr. S. Kivitie-Kallio, Children's Hospital, University of Helsinki, Stenbackinkatu 11, FIN-00290, Helsinki; Finland. TI - Granulocytopenia in Cohen syndrome. SO - British Journal of Haematology Vol 98(2) (pp 308-311), 1997. AB - Cohen syndrome is an autosomal recessive disorder characterized by mental retardation, microcephalia and typical craniofacial features, myopia and chorioretinal dystrophy. As some patients were reported to have leucopenia, we collected the haematological data of 26 Finnish Cohen patients. They all had experienced periods of isolated granulocytopenia from an early age. Granulocytopenia was mild to moderate, non-cyclic and never fatal. Most patients suffered from prolonged or repeated gingival or skin infections. We restudied 16 patients. Bone marrow examination revealed in all patients a normo- or hypercellular marrow, with a left-shifted granulopoiesis in 8/16 patients. The response to adrenaline stimulation was subnormal in 12/14 and hydrocortisone in 8/16 patients, but administration of rhG-CSF caused granulocytosis in the three patients studied. No bone marrow malignancies were seen. [References: 10] <46> UI - 1997193335 AU - Bonifazi E TI - What's new in pediatric dermatology. SO - European Journal of Pediatric Dermatology Vol 6(3) (pp 169-174), 1996. <47> UI - 1997171116 AU - Schmid D AU - Heinze G AU - Linnerth B AU - Tisljar K AU - Kusec R AU - Geissler K AU - Sillaber C AU - Laczika K AU - Mitterbauer M AU - Zochbauer S AU - Mannhalter C AU - Haas OA AU - Lechner K AU - Jager U AU - Gaiger A IN - A. Gaiger, First Dept. of Medicine, Division of Hematology, University of Vienna, Wahringer Gurtel 18-20, A-1090 Vienna; Austria. TI - Prognostic significance of WT1 gene expression at diagnosis in adult de novo acute myeloid leukemia. SO - Leukemia Vol 11(5) (pp 639-643), 1997. AB - We examined the presence of WT1-specific mRNA in bone marrow samples of 125 patients with de novo acute myeloid leukemia at diagnosis by two-step RT-PCR. The sensitivity of the assay was 1:100 (first step) and 1:10,000 (second step), respectively. WT1-specific mRNA was detected in 73% of patients. No correlation was found between WT1 gene expression and age, FAB type, LDH and karyotype at diagnosis. All patients were treated with standard induction chemotherapy. There was no difference in the CR rate between WT1-positive and -negative patients. Using Kaplan and Meier plot analysis we found no difference in disease-free survival (DFS) and overall survival (OS) between patients displaying the WT1 transcript and WT1-negative patients. Furthermore, no significant interactions between WT1 PCR results and age, FAB type, LDH and karyotype on DFS and OS were demonstrable using Cox regression analysis. Eight patients who were WT1 PCR positive at diagnosis and achieved complete hematological remission following chemotherapy were monitored during the course of the disease. Based on our limited data demonstrating a heterogenity of WT1 PCR results in CR we cannot draw any conclusions regarding the usefulness of WT1 PCR analysis for the early detection of relapse. We conclude that WT1 gene expression at diagnosis is not associated with specific characteristics of AML blast cells and is not a prognostic factor for CR, remission duration and overall survival in acute myeloid leukemia. [References: 29] <48> UI - 1997157567 AU - Nagler A AU - Ackerstein A AU - Or R AU - Naparstek E AU - Slavin S IN - Dr. A. Nagler, Bone Marrow Transplantation Dept., Hadassah University Hospital, POB 12000, Jerusalem 91120; Israel. TI - Immunotherapy with recombinant human interleukin-2 and recombinant interferon-alpha in lymphoma patients postautologous marrow or stem cell transplantation. SO - Blood Vol 89(11) (pp 3951-3959), 1997. AB - Immune-mediated effects appear to play a major role in controlling minimal residual disease (MRD). We, therefore, investigated the role of recombinant human interleukin-2 (rIL-2) given concomitantly with interferon- alpha (IFN-alpha) in malignant lymphoma (ML) patients with responding disease following autologous bone marrow or blood stem cell transplantation (ABSCT). Fifty-six patients were included in this investigation. Thirty-two patients had non-Hodgkin's lymphoma (NHL) and 24 patients had Hodgkin's disease (HD). Sixty-one patients (NHL 36, HD 25) served as historical controls. Patients from both groups had similar demographic characteristics, the same stage of disease at presentation, status of disease at transplantation, conditioning regimens, and type of transplant. rIL-2 and IFN-alpha were self-administered in two cycles beginning 2.5 to 10.5 months (median, 4 months) posttransplant and separated by a 4-week interval. Each cycle consisted of IFN-alpha subcutaneously (SC) 3 x 106 U/d x 5 d/wk combined with rIL-2 SC 3 to 6 IU/m2/d x 5 d/wk for 4 weeks. The incidence of survival and disease-free survival (DFS) was significantly higher in the group under investigation than in the historical controls (P < .01). Of 56 patients with ML treated with IFN-alpha + rIL-2, 45 patients are DFS (80.4%) after a follow-up of 7 to 78 months (median, 34 months), whereas in the historical controls, 32 of 61 (52.5%) patients are disease free, in a follow-up of 4 to 84 months (median, 23 months) posttransplant (P < .01). Our preliminary results are encouraging and suggest that home administered immunotherapy with IFN-alpha and rIL-2 is relatively well tolerated and may intensify remission in ML patients with MRD following ABSCT. [References: 78] <49> UI - 1997117502 AU - Haas R AU - Schmid H AU - Hahn U AU - Hohaus S AU - Goldschmidt H AU - Murea S AU - Kaufmann M AU - Wannenmacher M AU - Wallwiener D AU - Bastert G AU - Hunstein W IN - R. Haas, Department of Internal Medicine V, University of Heidelberg, Hospitalstr. 3, 69115 Heidelberg; Germany. TI - Tandem high-dose therapy with ifosfamide, epirubicin, carboplatin and peripheral blood stem cell support is an effective, adjuvant treatment for high-risk primary breast cancer. SO - European Journal of Cancer Part A Vol 33(3) (pp 372-378), 1997. AB - We evaluated the therapeutic efficacy and toxicity of a tandem high-dose therapy with peripheral blood stem cell (PBSC) support in 40 patients with high-risk, primary breast cancer (stage II-III) and involvement of ten or more positive axillary lymph nodes. Their median age was 44 years (range 23-56). Two cycles of cytotoxic chemotherapy with ifosfamide (10000 mg/m2) and epirubicin (100 mg/m2) were administered. Granulocyte colony-stimulating factor (G-CSF) was given to hasten neutrophil reconstitution and to mobilise PBSC during marrow recovery. Leukaphereses were performed following the first and/or second cycle. Tandem high-dose therapy consisted of two cycles with ifosfamide (15 or 12 g/m2) and epirubicin (150 mg/m2), while carboplatin (900 mg/m2) was added for the last 24 patients included. Using an immunocytochemical method, two of 11 patients had cytokeratin-positive tumour cells in three leukapheresis products that were collected following the first G-CSF-supported cycle with ifosfamide and epirubicin, whereas only two harvests obtained following the second cycle in 26 patients contained cytokeratin-positive tumour cells. The number of CD34+ cells/kg re-infused following both high-dose cycles was similar (4.20 + 0.29 x 106, first cycle and 5.25 + 0.63 x 106, second cycle), and no notable difference was noted in the speed of haematological reconstitution. An absolute neutrophil count (ANC) of 0.5 x 109/l was reached after a median time of 13 days, while an unsupported platelet count of 20.0 x 109/l was achieved after a median time of 8 (first cycle) and 9 (second cycle) days post-transplantation. Patients autografted with more than 7.5 x 106 CD34+ cells/kg had platelet counts above 20 x 109/l within less than 10 days. 6 patients relapsed between 7 and 11 months (median 8 months) post-transplantation. 37 patients are alive and in remission with a median follow-up time of 11 months (range 1-38). This translates into a probability of disease-free survival (DFS) of 77% (95% CI 32-95%) at 38 months. The probability of overall survival is 85%, since 3 patients with local relapse achieved a second complete remission following surgery and involved-field radiotherapy. In conclusion, a sequential high-dose therapy including ifosfamide, epirubicin, carboplatin and PBSC support is well tolerated and effective in patients with high-risk primary breast cancer. Involved-field irradiation should be performed posttransplantation to reduce the risk of local relapse. [References: 24] <50> UI - 1997117124 AU - Legros M AU - Dauplat J AU - Fleury J AU - Cure H AU - Suzanne F AU - Chassagne J AU - Bay JO AU - Sol C AU - Canis M AU - Condat P AU - Choufi B AU - Tavernier F AU - Glenat C AU - Chollet P AU - Plagne R IN - Dr. M. Legros, Centre Jean Perrin, 58, rue Montalembert-BP 392, 63011 Clermont-Ferrand, Cedex 1; France. E-Mail: rplagne@cjp.u-clermontl.fr. TI - High-dose chemotherapy with hematopoietic rescue in patients with stage III to IV ovarian cancer: Long-term results. SO - Journal of Clinical Oncology Vol 15(4) (pp 1302-1308), 1997. AB - Purpose: A series of 53 patients with poor-prognosis epithelial ovarian cancer treated with high-dose chemotherapy (HDC) followed by hematopoietic rescue was retrospectively studied from the day of diagnosis far toxicity and long-term survival analysis. Patients and Methods: Patients were treated with surgery followed by cisplatin combination chemotherapy. After second-look operation (SLO), HDC was administered: 23 patients received melphalan (140 mg/m2 on day 1) and 30 patients received a combination of carboplatin (400 mg/m2 on days 1 to 4) and cyclophosphamide (1.6 g/m2 on days 1 to 4). After HDC, autologous stem-cell transplantation was performed for hematologic support. Results: One patient died of cardiac failure after HDC, but the acute toxicity was acceptable for the other patients. With a median follow- up of 81.5 months, the 5-year overall survival rate for the 53 patients was 59.9% and the disease-free survival (DFS) rate at 5 years was 23.6%. Twenty- four patients (45.3%) were alive, 12 with no evidence of disease and 12 with recurrent disease. The best results were achieved in 19 patients with pathologic complete response at SLO (74.2% 5-year overall survival; 32.8% 5- year DFS). Conclusion: HDC followed by autologous stem-cell support is a well-tolerated therapeutic approach for patients with poor-prognosis ovarian carcinoma. In this report, the 59.9% survival of 53 patients at 5 years must be compared to the 20% to 30% 5-year survival observed after conventional therapy. These results should be confirmed by an ongoing prospective randomized trial. [References: 37] <51> UI - 1997109938 AU - Cahill MR AU - Colvin BT IN - M.R. Cahill, Haemophilia Comprehensive Care Ctr., Royal London Hospital, London E1 1BB; United Kingdom. TI - Haemophilia. SO - Postgraduate Medical Journal Vol 73(858) (pp 201-206), 1997. AB - Although the nature of haemophilia has been understood for thousands of years, knowledge of its molecular genetics is recent. These X-linked bleeding disorders have diverse underlying DNA defects and, in 1992, DNA inversion within the X chromosome was found to explain half of the most serious cases of haemophilia A. The life-span and quality-of-life for patients with haemophilia had improved steadily throughout the early 1980s but the principal cause of death remained intracranial haemorrhage until the epidemic of HIV infection due to contaminated factor concentrates. Infection with hepatitis C virus is almost universal for patients treated with clotting factors before 1985. No curative treatment is available for hepatitis C at present. Knowledge of the transmission of viruses in concentrates has led to important developments in processing techniques to eliminate them. Recombinant technology has produced factor VIII and, more recently, factor M concentrate which is likely to be very safe. Development of inhibitors to factor concentrates (especially factor VII) remains one of the most serious complications of haemophilia. The variety of treatments available testifies to the lack of a single universally efficacious one. The use of prophylactic treatment has been conclusively demonstrated to result in a preservation of joint function in severely affected patients who might otherwise develop significant joint problems. The many facets of the care of patients with severe haemophilia, ranging from dental care to genetic counselling, can be advantageously co-ordinated in a haemophilia comprehensive care centre. [References: 43] <52> UI - 1997108545 AU - Sieving DL IN - D.L. Sieving, Computation and Neural Systems Group, California Institute of Technology, M.C. 136-93, 1200 East California Street, Pasadena, CA 91125; United States. TI - An engineering approach to miogravity syndrome. SO - Aviation Space & Environmental Medicine Vol 68(4) (pp 346-348), 1997. AB - The human species is rapidly expanding. Barring global catastrophe and unnatural constraints, it will, in a brief time on the scale of natural history, fill the uttermost reaches of the solar system. The beachhead established by President Kennedy's lunar program will lead to lunar, Martian and free space settlements in the next century. In a single generation of those who call them home, the constant 9.81 m . s-2 pull of Earth's gravity, which has influenced the evolution and development of terrestrial life forms for billions of years, will fade from common experience. Miogravity syndrome, a prognosticated complex arising in reduced gravity environments such as the surfaces of the Moon and Mars and principally encompassing muscle atrophy, cardiovascular deconditioning and bone demineralization, stands to replace physics and rocketry as the fundamental challenge of interplanetary astronautics. Mirroring our past few million years of changing climate and resources, the mobility of humans between diverse gravitational environments on the high frontier will critically depend on our ability to adapt. Tomorrow, as ever, a mushrooming penchant for toolmaking will spearhead the human career. [References: 25] <53> UI - 1997105110 AU - Daculsi G AU - Bouler J-M AU - LeGeros RZ IN - G. Daculsi, Centre Recherche Interdisciplinaire, Tissus Calcifies et les Biomateriaux, Faculte de Chirurgie Dentaire, 44042 Nantes Cedex 01; France. TI - Adaptive crystal formation in normal and pathological calcifications in synthetic calcium phosphate and related biomaterials. SO - International Review of Cytology Vol 172 (pp 129-191), 1997. AB - Mineralization and crystal deposition are natural phenomena widely distributed in biological systems from protozoa to mammals. In mammals, normal and pathological calcifications are observed in bones, teeth, and soft tissues or cartilage. We review studies on the adaptive apatite crystal formation in enamel compared with those in other calcified tissues (e.g., dentin, bone, and fish enameloids) and in pathological calcifications, demonstrating the adaptation of these crystals (in terms of crystallinity and orientation) to specific tissues that vary in functions or vary in normal or diseased conditions. The roles of minor elements, such as carbonate, magnesium, fluoride, hydrogen phosphate, pyrophosphate, and strontium ions, on the formation and transformation of biologically relevant calcium phosphates are summarized. Another adaptative process of crystals in biology concerns the recent development of calcium phosphate ceramics and other related biomaterials for bone graft. Bone graft materials are available as alternatives to autogeneous bone for repair, substitution, or augmentation. This paper discusses the adaptive crystal formation in mineralized tissues induced by calcium phosphate and related bone graft biomaterials during bone repair. [References: 324] <54> UI - 1997019175 AU - De la Rubia J AU - Sanz GF AU - Martin G AU - Sempere A AU - Picon I AU - Carral A AU - Larrea L AU - Martinez J AU - Soler MA AU - Bonanad S AU - Lopez F AU - Jarque I AU - Sanz MA IN - Dr. M.A. Sanz, Servicio de Hematologia, Hospital Universitario La Fe, Av Campanar 21, 46009 Valencia; Spain. TI - Autologous bone marrow transplantation for patients with acute myeloblastic leukemia in relapse after autologous blood stem cell transplantation. SO - Bone Marrow Transplantation Vol 18(6) (pp 1167-1173), 1996. AB - Leukemic relapse remains the most frequent reason for treatment failure in patients with acute myeloblastic leukemia (AML) treated with autologous blood stem cell transplantation (ABSCT). The aim of this study was to evaluate the possible role of autologous bone marrow transplant (ABMT) in patients with AML who relapse after ABSCT. Eighteen consecutive patients were enrolled in the study. At ABMT, 17 patients were in untreated relapse and one was in third complete remission (CR). The preparative regimen was BAVC, and consisted of BCNU 800 mg/m2 on day -6, M-AMSA 150 mg/m2/day on days -5 to -3, VP-16 150 mg/m2/day on days -5 to -3 and Ara-C 300 mg/m2/day on days -5 to -3. There were two regimen-related deaths (11%). Thirteen out of 17 patients in untreated relapse before ABMT achieved CR (76%). The cumulative risk of relapse was 58 +/- 13% at 3 years. Seven patients are in CR between 7+ and 53+ months, with a disease-free survival (DFS) probability of 36 +/- 12% at 3 years. The probability of DFS after ABMT was clearly higher in those patients relapsing later than 7 months after the first autograft (52%) than in patients relapsing earlier (20%) (P = 0.02). In a significant proportion of patients, remission duration was clearly longer after ABMT than ABSCT. We conclude that BAVC conditioning followed by ABMT is associated with a low treatment-related toxicity and results in prolonged DFS in a substantial number of AML patients who relapse after ABSCT. Until better therapeutic options become available, ABMT in untreated relapse is a useful alternative in this group of very poor-risk patients. [References: 37] <55> UI - 1997008125 AU - Rueda F AU - Marti F AU - Pardo N AU - Badell I AU - Peiro M AU - Bertran E AU - Villen E AU - Garcia J AU - Cubells J IN - F. Rueda, Cryobiology/Cell Therapy Department, Cancer Research Institute, Hospital Duran i Reynals, Autovia de Castelldefels, Km 2.7, 08907 L'Hosp. Llobregat (Barcelona); Spain. TI - Interleukin-2 in neuroblastoma: Clinical perspectives based on biological studies. SO - Cancer Biotherapy & Radiopharmaceuticals Vol 11(5) (pp 303-308), 1996. AB - Stage IV neuroblastoma (NB) is a disease with a poor prognosis. Chemotherapeutical intensification and hematological rescue with autologous bone marrow transplantation (ABMT) achieve some complete remissions (CR), but most patients relapse during the first year. Immunotherapy could be an alternative in this situation of high risk of relapse due to residual disease and ABMT-related immunodepression. Ten stage IV NB patients in CR or very good partial remission have been treated with recurrent 5-day cycles of high doses of Interleukin-2 (IL2) after ABMT throughout one year (usually 5-6 cycles). Natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic activities, as well as phenotype and number of circulating NK cells were determined, before and after each course of IL2 treatment. The effects promoted by IL2 varied during treatment: early cycles of IL2 reduced a great extent of cell expansion, mainly on CD3-/CD16-/CD56(+bright) and CD8(+dim) cell phenotypes; conversely, late courses of IL2 promoted higher NK cytotoxic activity but a lesser increase on circulating NK cells. The induction of LAK activity did not significantly differ from early and late IL2 treatments. Clinical results are still inconclusive due to the small number of patients. The median follow-up of patients treated with IL2 is 24 months and the disease free survival (DFS) probability is 0.80 +/- 0.12 vs 0.16 +/- 0.15 from a historical control with identical treatment, but in the absence of IL2 treatment (p<0.005). IL2 treatment-related toxicity was mild and no interruption of the treatment was required. Extremely accurate hydric control was carried out to avoid, as much as possible, the consequences of vascular leak syndrome, one of the most important toxic effects of IL2 treatment. The results presented here suggest an evolution of NK activity during IL2 treatment after ABMT, which should be taken into account for the designing of new immunotherapeutical protocols and opens a promising perspective in treatment of stage IV neuroblastoma. <56> UI - 1996331868 AU - Esho Sawa T AU - Safar SB IN - Department of Surgery A, Hillerod Hospital,DK-3400 Hillerod; Denmark. TI - Pathological fracture: A common presentation of primary hyperparathyroidism in Iraq. SO - European Journal of Surgery Vol 162(10) (pp 777-781), 1996. AB - Objective: To describe our experience with severe primary hyperparathyroidism. Design: Prospective open study. Setting: City hospital, Iraq. Subjects: 15 patients with confirmed severe hyperparathyroidism operated on during the period 1985-92. Intervention: Neck exploration was performed for all patients. Main outcome measures: Morbidity, mortality, and outcome. Results: The peak incidences were in the age groups 20-29. 10 patients presented with pathological fractures. Plasma parathyroid hormone concentrations were raised in all 15 patients. 14 patients had solitary adenomas, and the remaining one had three adenomas. One patient developed persistent hypocalcaemia that required permanent vitamin D supplementation, and 12 patients developed transient postoperative hypocalcaemia and were treated with calcium and vitamin D supplements either orally or intravenously until they were free of symptoms. Two patients died postoperatively, one of respiratory failure and one of haemorrhage from a bleeding duodenal ulcer. Conclusion: Primary hyperparathyroidism is an underdiagnosed disorder in Iraq, and most patients present with advanced disease. Surgical treatment is indicated and the results are good. <57> UI - 1996273921 AU - Pashley DH IN - Department of Oral Biology, School of Dentistry, Medical College of Georgia,Augusta, GA 30912-1129; United States. TI - Dynamics of the pulpo-dentin complex. SO - Critical Reviews in Oral Biology & Medicine Vol 7(2) (pp 104-133), 1996. AB - Dentin has a relatively high water content due to its tubular structure. Once dentin is exposed, this intratubular water is free to move in response to thermal osmotic, evaporative or tactile stimuli. Fluid shifts across dentin are thought to cause sufficient shear forces on odontoblasts, nerve endings, nearby fibroblasts, and blood vessels to cause significant mechanical irritation, disruption, or damage, depending on the magnitude of the fluid shift. Even in the absence of fluid shifts, the water-filled tubules provide diffusion channels for noxious (i.e., bacterial products) substances which diffuse inward toward the pulp, where they can activate the immune system, provide chemotactic stimuli, cytokine production, and produce pain and pulpal inflammation. Viewed from this perspective, dentin is a poor barrier to external irritants. However pulpal tissues react to these challenges by increasing the activity of nerves, blood vessels the immune system and interstitial fluid turnover, to make the exposed dentin less permeable either physiologically, via increased outward fluid flow, or microscopically by lining tubules with proteins, mineral deposits, or tertiary dentin, thereby enhancing the barrier properties of dentin and providing additional protection to pulpal tissues. These reactions involve dentin and pulp, both in the initiation of the processes and in their resolution. These responses of the dental pulp to irritation of dentin demonstrate the dynamic nature of the pulpo-dentin complex. <58> UI - 1996189972 AU - Ferrari AM AU - Byers MR IN - Department of Anesthesiology, University of Washington, Box 356540,Seattle, WA 98195-6540; United States. TI - Chronic dexamethasone treatment and its effects on sensory neuropeptides, pulpal injury reactions and reparative dentin. SO - Brain Research Vol 723(1-2) (pp 125-134), 1996. AB - Initial sensory nerve reactions to dental injuries include terminal sprouting and intensified immunoreactivity for calcitonin gene-related peptide (CGRP) and substance P (SP); those reactions are reduced at 4 days after injury when rats are treated daily with dexamethasone (DEX). Here we have analyzed long-term effects of DEX (daily, 0.2 mg/kg) on wound healing, sensory nerve sprouting, and CGRP/SP intensity at 7-14 days after cavity preparation. All DEX treated rats had loss of appetite and stopped growing during the postoperative periods while controls had normal postoperative growth. After 7-14 days, CGRP immunoreactivity (IR) was decreased to one-third of normal (P < 0.05) compared to vehicle in both the intact and injured molar pulp, and SP also decreased, but the neuropeptide intensity in adjacent periodontal innervation was not changed. Pulpal injury and inflammation were reduced by DEX treatment, but reparative dentin was formed just as well in the DEX rats as in the vehicle group. When the injured teeth formed fibrous dentin, there was sprouting of nerves towards that matrix, and DEX did not inhibit that reaction. The sprouts could contain intense neuropeptide immunoreactivity in DEX rats even though the CGRP/SP intensity in uninjured pulp was reduced. We conclude that (1) chronic DEX treatment causes a generalized decrease in CGRP and SP neuropeptides in pulpal nerves but not in periodontal ligament; (2) it reduces abscess formation in injured teeth; (3) it does not block reparative dentin formation; and (4) it does not block sprouting of pulpal nerves towards fibrous dentin. The selective loss of pulpal neuropeptides CGRP and SP during dexamethasone treatment may be caused by reduced dental function since there was substantial loss of appetite and chronic weight loss during the 1-2 week treatment periods. <59> UI - 1996186505 AU - DiMichele D IN - RCHTC, Cornell Medical Center, New York Hospital, 525 East 68th Street,New York, NY 10021; United States. TI - Hemophilia 1996: New approach to an old disease. SO - Pediatric Clinics of North America Vol 43(3) (pp 709-736), 1996. AB - The history of hemophilia diagnosis and therapy has been a turbulent one. We are coming full circle, back to the use of genetics as the main diagnostic tool for this disease. Therapeutically, the retroviruses that ravaged one generation of hemophiliac patients now may participate in the cure for the next generation. The hemophilia community hopes that the future of hemophilia care will follow a course guided by this modified quote from James Russell Lowell: 'New times demand new measures, and men [and women]. As the world advances and in time outgrows the laws that in our fathers' [and mothers'] days were the best, doubtless after us some purer scheme will be shaped out by wiser men [and women] than we, made wiser by the steady growth of truth.' <60> UI - 1996143157 AU - Kobayashi S AU - Eftekhar NS AU - Terayama K IN - Department of Orthopaedic Surgery, Shinshu Univ. School of Medicine, Asahi 3-1-1,Matsumoto 390; Japan. TI - Long term bone remodeling around the Charnley femoral prostheses. SO - Clinical Orthopaedics & Related Research Issue 326 (pp 162-173), 1996. AB - Femoral bone remodeling after total hip replacement was studied by following patients who received 326 Charnley femoral prostheses for 10 to 20 years (mean, 13.3 years). The radiographic state of bone remodeling was visually assessed and measured with a digitizer. Demineralization that started proximally and then progressed distally caused cortical thinning, which correlated with widening of the intramedullary canal, not with changes that developed in the periosteal width, and occurred in the medial femoral neck, around the proximal half of the stem, and around the distal half in 87%, 33%, and 10%, respectively. Cortical thinning around the distal half of the stem was always accompanied by proximal thinning, and extensive cortical thinning (both proximal and distal) correlated with both lower clinical scores and radiologic loosening of the femoral prosthesis. A low canal flare index of Noble, a large canal width, and a patient age of 60 years or more were risk factors for extensive cortical thinning. Accelerated polyethylene wear was related to resorption of the medial femoral neck but not to cortical thinning or radiological loosening. Cortical thickening occurred only around the distal half of the stem in 29%. These findings establish a basis for the performance of cemented femoral prostheses, and allow comparison of bone remodeling when evaluating other femoral prostheses. <61> UI - 1996124365 AU - Liu T-Z AU - Yang H-L AU - Chan C-P AU - Pan W-L AU - Wu SK IN - School of Medical Technology, Chang Gung College of Med./Technol., 259 Wen-Hwa 1st Road,Kwei-Shan, Taoyuan 333; Taiwan. TI - Induction of superoxide dismutase isozymes by tumor necrosis factor-alpha and lipopolysaccharide in cultured normal and hyperplastic gingival fibroblasts. SO - Journal of the Formosan Medical Association Vol 95(3) (pp 236-240), 1996. AB - To determine whether lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) are involved in the induction of superoxide dismutase (SOD) in gingival tissue, we examined their effect on induction of SOD isozymes in cultured normal (NGF) and phenytoin-induced hyperplastic (PHF) gingival fibroblasts. Treatment of both NGFs and PHFs with 10 to 50 ng/mL TNF-alpha for 24 hours increased the level of manganese SOD (MnSOD) to as much as four times the level of untreated cultures. PHFs, but not NGFs, were shown to be responsive to TNF-alpha in eliciting a significant increase in copper-zinc SOD (Cu/ZnSOD), albeit in a lesser amount than MnSOD. Additionally, treatment of both types of cells with 5 to 50 mg/mL of LPS for 24 hours also elicited an increase in the level of MnSOD. Again, an LPS-induced increase in Cu/ZnSOD levels could only be demonstrated in PHFs, but not in NGFs. These observations were further confirmed by comparing the achromatic bands associated with SOD isozymes exhibited in the electrophoretogram using a nondenaturing polyacrylamide electrophoresis technique. These results indicate that TNF-alpha and LPS were capable of inducing both MnSOD and Cu/ZnSOD simultaneously in PHF fibroblasts. PHFs may be inherently more capable than NGFs in combating oxidative stress. <62> UI - 1996132024 AU - Welte K AU - Dale D IN - Dept.