Prognosis versus actual outcome. III. The effectiveness of clinical parameters in accurately predicting tooth survival

Tooth loss for 100 treated periodontal patients (2,509 teeth) under maintenance care was evaluated to determine the effectiveness of commonly taught clinical parameters utilized in the assignment of prognosis in accurately predicting tooth survival. Previous studies in this series evaluated prognosis as a surrogate variable representing the condition of the tooth at a particular point. In this study, survival analysis was used to evaluate the relationship of these common clinical parameters to an actual end point, tooth loss. Robust log rank tests indicated that initial probing depth, initial furcation involvement, initial mobility, initial crown-to-root ratio, and initial root form were all associated with tooth loss. In addition, smoking and increased initial bone loss were both found to be associated with increased risk of tooth loss while fixed abutment status was associated with a decreased risk of tooth loss. A Cox proportional hazards regression model showed that initial probing depth, initial furcation involvement, initial mobility, initial percent bone loss, presence of a parafunctional habit without a biteguard, and smoking were all associated with an increased risk of tooth loss. This model suggests that patients are twice as likely to loose their teeth if there is increasing mobility, if they have a parafunctional habit and do not wear a biteguard, or if they smoke. From these data there does appear to be a relationship between the assigned prognosis and tooth loss. Teeth with worse prognosis have a worse survival rate, but the commonly taught clinical parameters used in the traditional method of assignment of prognosis do not adequately explain that relationship. Furthermore, initial prognosis did not adequately explain the condition of the tooth or accurately predict the tooth's survival. These results seem to indicate that the effect of these clinical parameters on tooth survival is only partially reflected in the assigned prognosis initially, suggesting that perhaps some of the clinical parameters should be weighed more heavily than others when assigning prognosis. Further studies are needed to develop a more accurate method for the assignment of prognosis.     

Incremental value of myocardial perfusion scintigraphy in prognosis and outcomes of patients with coronary artery disease

The concept of incremental value in prognosis and outcome of patients with coronary artery disease is important to the field of noninvasive imaging. Because these tests are expensive, they should be held to the standard of demonstrating a statistical improvement over the information provided by clinical assessment and treadmill testing. Responding to the demand for cost-effective applications of myocardial perfusion scintigraphy, a large amount of research has recently been devoted to defining specific patient subsets in which incremental value exists for scintigraphy. Subsets thus far demonstrated to benefit incrementally include those men and women referred for possible coronary artery disease, with known coronary artery disease, and after percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, unstable angina, or recent infarction. Incremental cost savings also apply to these subsets except for patients with normal ECGs at rest and less than 15% likelihood for significant coronary artery disease.     

Prolongation of the p53 response to DNA strand breaks in cells depleted of PARP by antisense RNA expression

The observation that 3-aminobenzamide, which inhibits a variety of ADP-ribose transferases, prolongs the gamma-irradiation-induced increase in intracellular p53 concentration suggested that one or more of such enzymes may determine the duration of the p53 response during G1 arrest. The role of poly(ADP-ribose) polymerase (PARP), an abundant nuclear enzyme activated by DNA strand breaks, in the p53 response to y-irradiation was investigated in Burkitt's lymphoma AG876 cells stably transfected with an inducible PARP antisense construct. Immunoblot analysis revealed that the cellular content of PARP was reduced to virtually undetectable levels after incubation of transfected cells for 72 h with the inducer dexamethasone. In noninduced antisense cells, the p53 concentration reached a maximum 2 h after exposure to 6.3 Gy of gamma-radiation and returned to control values by 4 h. In contrast, the p53 response in PARP-depleted antisense cells peaked at 4 h, with the levels of p53 remaining elevated for up to 12 h after y-irradiation. The maximal increase in p53 concentration was similar in both induced and noninduced cells. These results thus indicate that PARP activity, in part, determines the duration, but not the magnitude, of the p53 response to DNA damage.     

Pharmacology and intracellular signaling mechanisms of the native human orphan receptor BRS-3 in lung cancer cells

Neither the native ligand nor the cell biology of the bombesin (Bn)-related orphan receptor subtype 3 (BRS-3) is known. In this study, we used RT-PCR to identify two human lung cancer lines that contain sufficient numbers of native hBRS-3 to allow study: NCI-N417 and NCI-H720. In both cell lines, [DPhe6,betaAla11,Phe13, Nle14]Bn(6-14) stimulates [3H]inositol phosphate. In NCI-N417 cells, binding of 125I-[DTyr6,betaAla11,Phe13,Nle14]Bn(6-14) was saturable and high-affinity. [DPhe6,betaAla11,Phe13,Nle14]Bn(6-14) stimulated phospholipase D activity and a concentration-dependent release of [3H]inositol phosphate (EC50 = 25 nM) and intracellular calcium (EC50 = 14 nM); the increases in intracellular calcium were primarily from intracellular stores. hBRS-3 activation was not coupled to changes in adenylate cyclase activity, [3H]-thymidine incorporation or cell proliferation. No naturally occurring Bn-related peptides bound or activated the hBRS-3 with high affinity. Four different bombesin receptor antagonists inhibited increases in [3H]inositol phosphate. Using cytosensor microphysiometry, we found that [DPhe6,betaAla11,Phe13, Nle14]Bn(6-14) caused concentration-dependent acidification. The results show that native hBRS-3 receptors couple to phospholipases C and D but not to adenylate cyclase and that they stimulate mobilization of intracellular calcium and increase metabolism but not growth. The discovery of human cell lines with native, functional BRS-3 receptors, of new leads for a more hBRS-3-specific antagonist and of the validity of microphysiometry as an assay has yielded important tools that can be used for the identification of a native ligand for hBRS-3 and for the characterization of BRS-3-mediated biological responses.     

Epidemiology of osteosarcoma and Ewing's sarcoma in childhood: a study of 305 cases by the Children's Cancer Group

BACKGROUND: The Children's Cancer Group conducted a case-control study to determine the role of a broad range of environmental and familial factors in the etiology of Ewing's sarcoma and osteosarcoma in children. These factors included radiation exposure and, for children with osteosarcoma, parental exposure to beryllium. METHODS: The parents of 152 children with osteosarcoma and 153 children with Ewing's sarcoma were interviewed by telephone. Controls were obtained by random digit dialing and were matched to cases by age and race. RESULTS: Female osteosarcoma patients had earlier onset of breast development (age 11.4 vs. 11.8 years, P=0.03) and menarche (age 12.1 vs. 12.5 years, P=0.002) but no significant differences in growth, whereas male osteosarcoma patients were similar in age at the onset of secondary sexual characteristics but reported significantly less weight gain during their growth spurt (6.6 vs. 11.7 kg, P=0.003). For children with Ewing's sarcoma, the growth spurt began earlier (age 12.1 vs. 12.7 years, P=0.12) and resulted in less weight and height gain (5.2 vs. 9.7 kg, P=0.002, and 10.2 vs. 12.7 cm, P=0.02, respectively) for males, but no differences were observed among females. For factors not related to growth and development (including a wide range of occupational, medical, and household exposures), there was little evidence of an etiologic role with respect to either tumor type. CONCLUSIONS: Differences between cases and controls with respect to growth and development showed no consistent pattern. This study did not identify any important risk factors for either type of childhood bone tumor.     

Assessment of the biodistribution and metabolism of 5-fluorouracil as monitored by 18F PET and 19F MRI: a comparative animal study

The effective clinical use of the anticancer drug 5-fluorouracil (5-FU) requires the non-invasive assessment of its transport and metabolism, particularly in the tumor and the liver, where the drug is catabolized to alpha-fluoro-beta-alanine (FBAL). In this study, the potentials and limitations of dynamic 18F PET and metabolic 19F MRI examinations for noninvasive 5-FU monitoring were investigated in ACI and Buffalo rats with transplanted MH3924A and TC5123 Morris hepatomas, respectively. Selective 5-[19F]FU and [19F]FBAL MR images were acquired 5 and 70 min after 5-FU injection using a CHESS MRI sequence. After administration of 5-[18F]FU, the kinetics of the regional 5-[18F]FU uptake were measured by dynamic PET scanning over 120 min. To allow a comparison between PET and MRI data, standardized uptake values (SUV) were computed at the same points in time. The TC5123 hepatoma showed a significantly (p < 0.002) higher mean SUV at 5 and 70 min post-5-FU injection than the MH3924A cell lines, whereas there were no significant differences between the mean SUV measured in the liver of both animal populations. In contrast to the PET data, no significant differences in the mean 5-[19F]FU and [19F]FBAL MR signal values in the tumor of both models were observed. The MR images, however, yielded the additional information that 5-FU is converted to FBAL only in the liver and not in the hepatomas.