Modulation of growth factor binding properties of a2-macroglobulin by enzyme therapy

Purpose: To investigate the binding of transforming growth factor-beta (TGF-?) to human a2-macroglobulin upon oral treatment of patients with proteases. Methods: Volunteers were given a cocktail of active proteinases (Phlogenzym) composed of trypsin, bromelain and the additive rutoside orally over a period of 7 days at low dose followed by a bolus application. Before and after medication plasma was immediately withdrawn and binding of ¹²⁵I-TGF-? to the proteinase inhibitor a2-macroglobulin was determined by electrophoresis and ?-counting. Cell culture experiments were performed to study the effect of transformed a2-macroglobulin on TGF-?-stimulated proliferation of skin fibroblasts. Results: Ingestion of proteinases was found to trigger the formation of intermediate forms of a2-macroglobulin displaying high affinity to TGF-?. Maximum binding of TGF-? was observed 1-2 h after bolus ingestion, and steadily levelled off with time. In vitro experiments demonstrated that complex formation of diverse proteinases (trypsin, a-chymotrypsin, bromelain and plasmin) with a2-macroglobulin conferred binding of ¹²⁵I-TGF-?. a2-Macroglobulin transformed by methylamine or proteinases was found to abolish the TGF-? effect on fibroblasts in cell culture. Conclusions: Intestinal absorption of proteinases triggers the formation of TGF-? binding species of a2-macroglobulin in blood. Mediated by this process high concentrations of TGF-? might be reduced via enhanced clearance of a2-macroglobulin-TGF-? complexes. Thus, proteinase therapy may have beneficial effects in treatment of fibrosis and certain cancers accompanied by excessively high TGF-? concentrations.     

Racial differences in the survival of childhood B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group Study.

PURPOSE: We conducted a historic cohort study to test the hypothesis that, after adjustment for biologic factors, African-American (AA) children and Spanish surname (SS) children with newly diagnosed B-precursor acute lymphoblastic leukemia had lower survival than did comparable white children. PATIENTS AND METHODS: From 1981 to 1994, 4,061 white, 518 AA, and 507 SS children aged 1 to 20 years were treated on three successive Pediatric Oncology Group multicenter randomized clinical trials. RESULTS: AA and SS patients were more likely to have adverse prognostic features at diagnosis and lower survival than were white patients. The 5-year cumulative survival rates were (probability +/- SE) 81.9% +/- 0.6%, 68.6% +/- 2.1%, and 74.9% +/- 2.0% for white, AA, and SS children, respectively. Adjusting for age, leukocyte count, sex, era of treatment, and leukemia blast cell ploidy, we found that AA children had a 42% excess mortality rate compared with white children (proportional hazards ratio [PHR] = 1.42; 95% confidence interval [CI], 1.12 to 1. 80), and SS children had a 33% excess mortality rate compared with white children (PHR = 1.33; 95% CI, 1.19 to 1.49). CONCLUSION: Clinical presentation, tumor biology, and deviations from prescribed therapy did not explain the differences in survival and event-free survival that we observed, although differences seem to be diminishing over time with improvements in therapy. The disparity in outcome for AA and SS children is most likely related to variations in chemotherapeutic response to therapy and not to compliance. Further improvements in outcome may require individualized dosing based on specific pharmacogenetic profiles, especially for AA and SS children.     

Resorbable triangular plate for osteosynthesis of fractures of the condylar neck

We describe a new design of resorbable plate for use in the treatment of fractures of the condylar neck, and report the outcome of initial treatment in two patients.     

Surface roughness of zirconia for full-contour crowns after clinically simulated grinding and polishing

The aim of this study was to evaluate the effect of controlled intraoral grinding and polishing on the roughness of full-contour zirconia compared to classical veneered zirconia. Thirty bar-shaped zirconia specimens were fabricated and divided into two groups（n515）. Fifteen specimens（group 1） were glazed and 15 specimens（group 2） were veneered with feldspathic ceramic and then glazed. Prior to grinding,maximum roughness depth（Rmax） values were measured using a profilometer, 5 times per specimen. Simulated clinical grinding and polishing were performed on the specimens under water coolant for 15 s and 2 N pressure. For grinding, NTI diamonds burs with grain sizes of 20 mm, 10 mm, and 7.5 mm were used sequentially. The ground surfaces were polished using NTI kits with coarse, medium and fine polishers. After each step, Rmaxvalues were determined. Differences between groups were examined using one-way analysis of variance（ANOVA）. The roughness of group 1 was significantly lower than that of group 2. The roughness increased significantly after coarse grinding in both groups. The results after glazing were similar to those obtained after fine grinding for non-veneered zirconia. However, fine-ground veneered zirconia had significantly higher roughness than venerred, glazed zirconia. No significant difference was found between fine-polished and glazed zirconia, but after the fine polishing of veneered zirconia, the roughness was significantly higher than after glazing.It can be concluded that for full-contour zirconia, fewer defects and lower roughness values resulted after grinding and polishing compared to veneered zirconia. After polishing zirconia, lower roughness values were achieved compared to glazing; more interesting was that the grinding of glazed zirconia using the NTI three-step system could deliver smooth surfaces comparable to untreated glazed zirconia surfaces.     

USING EXERCISE TESTING TO PROGNOSTICATE PATIENTS WITH HEART FAILURE: Which Parameter Should We Measure?

Peak oxygen consumption, as measured by direct gas exchange analysis during exercise testing, is well established as a powerful and independent predictor of risk for death among patients with chronic, but stable, heart failure. Although there is still some debate about whether peak oxygen consumption should be indexed against a predicted value and what the best cut-off point may be, most authorities agree that peak oxygen consumption is such a powerful predictor of outcome that it routinely should be incorporated into the evaluation of all ambulatory heart transplant candidates. A few recent studies have demonstrated that a hyperventilatory response to exercise, as measured by the VE/VCO2 slope, also may be a powerful and independent predictor of death; however, more large studies, with large numbers of end-points, will be needed before this measure can deservedly take a place alongside peak oxygen consumption as a primary component of the heart failure staging process.     

Long-term follow-up of parental adjustment following a child's death at home or hospital

The adjustment of parents whose children had died from cancer 6 to 8 years earlier was assessed using structured interviews and standardized inventories. Forty parents had participated in a home hospice program during the terminal phase of their child's illness whereas 22 were parents of children who died in the hospital. Home care parents reported significantly stronger relationships with spouse and remaining children, firmer religious convictions, more adequate coping abilities, and less residual guilt than non-home care parents. On the Minnesota Multiphasic Personality Inventory (MMPI), non-home care parents exhibited more frequent indications of maladjustment including somatization, depression, and interpersonal problems. The results confirm that the more optimal adjustment of home care parents which was first reported 5 years earlier has been maintained. Support and expansion of pediatric home hospice programs are strongly encouraged in light of the positive results of our longitudinal studies.