Preclinical animal study and clinical trail of modified extraoral craniofacial implants.

We report on our experience using a new endosseous implant designed to provide sufficient retention to various types of facial prostheses. In a preclinical animal experiment implants (N=12, 4 x 3.5 mm) were placed in the frontal calvarial region of nine adult pigs. The animals were sacrificed at 2, 4 and 8 weeks to evaluate the implant incorporation microradiographically. The clinical outcome and patient satisfaction of implant-retained prostheses were evaluated in a group of 10 patients with facial defects by using clinical assessment and standardized questionnaires for patients and relatives. In the prospective clinical study 33 identical modified implants for extraoral anchorage were placed for the fixation of various prostheses in the midfacial (eye, nose) and ear regions in the course of a clinical trial and observed over a follow-up period of 34 months. The bone-implant contact in the animal experiment reached 31% (+/-2) at 2 weeks, 39% (+/-1) after 4 weeks and 51% (+/-5) at 8 weeks. In the clinical trial, no implants were lost and all implants remained osseointegrated as confirmed clinically and radiographically, providing a stable prosthetic restoration. The analysis of the questionnaire indicates an improvement of the quality of life of patients with respect to aesthetic and psychological well-being. The results demonstrate that extraoral implants not only achieve sufficient osseointegration but also show good clinical handling and easy fixation possibilities for prosthetic anchorage.     

Apoptosis of myocytes and proliferation markers as prognostic factors in end-stage dilated cardiomyopathy.

INTRODUCTION: The aim of the study was to evaluate the role of apoptosis, proliferation markers, volume density of interstitium, and myofibril volume fraction for the prognosis in patients with end-stage dilated cardiomyopathy (DCM). METHODS: Endomyocardial biopsy was performed during open-heart surgery in 56 patients with end-stage DCM. Patients were divided into two groups, one group with shorter survival (24+/-9 months, mean+/-S.D.) and another group with survival of more than 7 years after operation. The TUNEL method was used for the detection of apoptosis, and immunohistochemical methods were used for the evaluation of inhibitor of apoptosis (bcl-2) and proliferation markers (PCNA and Ki-67). RESULTS: The increased percentage of apoptotic myocytes, decreased expression of bcl-2, and decreased expression of PCNA and Ki-67 antigen was found in the group with early mortality compared to that with longer survival. Myofibril volume fraction was lower and volume density of interstitium was higher in the group with early mortality compared to that with longer survival. CONCLUSION: Apoptosis, bcl-2 expression, and proliferation activity of myocytes, myofibril volume fraction, and volume density of interstitial tissue might be useful in predicting the prognosis (progressive vs. nonprogressive form) of patients with heart failure due to DCM.     

Kinetics of gene expression in murine cutaneous graft-versus-host disease

The kinetics of gene expression associated with the development of cutaneous graft-versus-host disease (GVHD) were examined in a mouse model of MHC-matched allogeneic hematopoietic stem cell transplantation. Ear skin was obtained from recipient mice with or without GVHD between 7 and 40 days after transplantation for histopathological analysis and gene expression profiling. Gene expression patterns were consistent with early infiltration and activation of CD8(+) T and mast cells, followed by CD4(+) T, natural killer, and myeloid cells. The sequential infiltration and activation of effector cells correlated with the histopathological development of cutaneous GVHD and was accompanied by up-regulated expression of many chemokines and their receptors (CXCL-1, -2, -9, and -10; CCL-2, -5, -6, -7, -8, -9, -11, and -19; CCR-1 and CCR-5), adhesion molecules (ICAM-1, CD18, Ly69, PSGL-1, VCAM-1), molecules involved in antigen processing and presentation (TAP1 and TAP2, MHC class I and II, CD80), regulators of apoptosis (granzyme B, caspase 7, Bak1, Bax, and BclII), interferon-inducible genes (STAT1, IRF-1, IIGP, GTPI, IGTP, Ifi202A), stimulators of fibroblast proliferation and matrix synthesis (interleukin-1beta, transforming growth factor-beta1), and markers of keratinocyte proliferation (keratins 5 and 6), and differentiation (small proline-rich proteins 2E and 1B). Many acute-phase proteins were up-regulated early in murine cutaneous GVHD including serum amyloid A2 (SAA2), SAA3, serpins a3g and a3n, secretory leukocyte protease inhibitor, and metallothioneins 1 and 2. The kinetics of gene expression were consistent with the evolution of cutaneous pathology as well as with current models of disease progression during cutaneous GVHD.     

Complex CGH alterations on chromosome arm 8p at candidate tumor suppressor gene loci in breast cancer cell lines

Loss of genetic material from chromosome arm 8p occurs frequently in human breast carcinomas, consistent with this region of the genome harboring one or more tumor suppressor genes (TSGs). We used the complementary techniques of microsatellite-based LOH, high-density FISH, and conventional CGH on 6 breast cancer cell lines (MCF7, SKBR3, T47D, MDA MB453, BT549, and BT474) to investigate the molecular cytogenetic changes occurring on chromosome 8 during tumorigenesis, with particular emphasis on 6 potential TSGs on 8p. We identified multiple alterations of chromosome 8, including partial or complete deletion of 8p or 8q, duplication of 8q, and isochromosome 8q. The detailed FISH analysis showed several complex rearrangements of 8p with differing breakpoints of varying proximity to the genes of interest. High rates of LOH were observed at markers adjacent to or within PCM1, DUSP4/MKP2, NKX3A, and DLC1, supporting their status as candidate TSGs. Due to the complex ploidy status of these cell lines, relative loss of 8p material detected by CGH did not always correlate with microsatellite-based LOH results. These results extend our understanding of the mechanisms accompanying the dysregulation of candidate tumor suppressor loci on chromosome arm 8p, and identify appropriate cellular systems for further investigation of their biological properties.     

A case of primary cutaneous cryptococcosis

The case of a 77-year-old man in whom a large digital ulcer with undermined edges was due to cutaneous infection byCryptococcus neoformans varietyneoformans serotype D, probably following direct inoculation, is reported. Long-term steroid treatment for chronic obstructive pulmonary disease may have been a risk factor. A 12-day course of intravenous amphotericin B at a cumulative dose of 750 mg, followed by oral fluconazole at a daily dose of 600 mg for six weeks, resulted in healing of the skin lesion. Manifestations of primary cutaneous cryptococcosis in immunocompetent or immunocompromised patients are reviewed     

Effect of BW B70C,a novel inhibitor of arachidonic acid 5-lipoxygenase,on allergen-induced bronchoconstriction and late-phase lung eosinophil accumulation in sensitised guinea-pigs

The actions of BW B70C, an orally available, biologically persistent and selective inhibitor of arachidonic acid 5-lipoxygenase, have been examined in two systems of anaphylaxis in actively sensitised guinea-pigsin vivo.In anaesthetised, artificially ventilated animals pretreated with mepyramine and indomethacin to leave only the “peptidoleukotriene-dependent” component (leukotrienes C4, D4 and E4) of the anaphylactic response, direct inhalation of nebulised, allergen resulted in a slowly developing bronchoconstriction which was prevented in a dose-dependent manner, by BW B70C (2–50 mg/kg p.o.) administered 1 or 6 h before challenge.In conscious animals fasted overnight and then pretreated with mepyramine to prevent death due to acute bronchial anaphylaxis, exposure to nebulised, allergen produced slight respiratory symptoms. When blood and lung samples were analysed 4–48 h after allergen provocation a sustained leukocytosis and pulmonary eosinophil accumulation were observed. In contrast, in food-replete conscious animals, the early respiratory symptoms were still observed upon allergen inhalation, but no significant blood leukocytosis or accumulation of eosinophils in the lungs occurred subsequently.The eosinophil influx induced by allergen in fasted animals was assessed both by histological examination and determination of tissue peroxidase content, two measures which demonstrated reasonable agreement. Administration of a single dose of BW B70C (10 mg/kg p.o.) 1 h prior to allergen challenge did not affect the subsequent eosinophil infiltration 24 h later, but 20 mg/kg given in divided doses (?1 and +12 h) produced 67% inhibition of cell accumulation. A single dose of 50 mg/kg (?1 h) had a similar effect (78% inhibition). The potent glucocorticosteroid betamethasone was used as a reference compound, and 4 mg/kg given as a divided dose (?1 and +7) fully inhibited lung inflammation assessed 24 h after provocation with allergen. BW B70C inhibited both acute and allergic bronchoconstriction and late-phase eosinophil accumulation subsequent to allergen inhalation in guinea-pigs. In view of the apparent requirement for sustained plasma levels of BW B70C in order to prevent late-phase eosinophil recruitment to the lung after a single challenge with allergen, it is unclear whether inhibition of 5-lipoxygenase underlies the observed anti-eosinophil accumulation effects of the compound, but the anti-bronchoconstrictor effects are consistent with the known inhibitory activity of BW B70C against 5-lipoxygenase.     

Allogeneic hematopoietic cell transplantation in chemotherapy‐induced aplasia in children with high‐risk acute myeloid leukemia or myelodysplasia

Relapse remains the most common cause of treatment failure after hematopoietic cell transplantation for acute myeloid leukemia. Inability to achieve hematologic complete remission has been a barrier to transplant for patients with refractory disease. We describe six children with refractory myeloid disease undergoing transplant in chemotherapy‐induced aplasia, as a strategy to facilitate curative therapy in refractory patients. Clofarabine‐ or high‐dose cytarabine‐based chemotherapy regimens were used to achieve marrow aplasia, followed by reduced‐intensity conditioning and allogeneic transplant before hematologic recovery. Long‐term disease control was achieved in five, with one transplant‐related mortality, suggesting the feasibility of this approach.     

Neonatal outcome in discordant eutrophic twins: twin growth.

OBJECTIVE: To compare maternal characteristics and neonatal outcome in discordant twin gestations (DT) and concordant twin gestation (CT). METHOD: Maternal and neonatal data base of live twins >25 weeks' gestation (N=351 pairs) were reviewed for antepartum complications, labor beginning, mode of delivery, neonatal complications, malformations and perinatal mortality. The chi-squared analysis and Student t-tests were used to analyze the differences between discordant and concordant premature and term twin pairs, and appropriate for gestational age (AGA) twins, separately. RESULTS: DT occurred in 15.1% of all twin pregnancies. In preterm and term DT there were significantly more elective cesareans. Growth discordance among preterm and term eutrophic twins was not connected with increased neonatal death or other complications, except higher incidence of early neurological signs in term DT. CONCLUSION: We strongly believed that prematurity and not discordant growth of eutrophic twins has important influence on neonatal outcome.