Modified LSA2-L2 treatment in 53 children with E-rosette-positive T- cell leukemia: results and prognostic factors (a Pediatric Oncology Group Study)

In an attempt to improve the poor outlook for children with T-cell leukemia (T-ALL), the Southwest Oncology Group, Pediatric Division, used a modified LSA2-L2 multidrug regimen to treat 53 patients with E- rosette-positive T-ALL. This regimen was chosen because of its demonstrated efficacy in T-cell (mediastinal) non-Hodgkin's lymphoma. Complete remission (CR) rate was 88%. Range of follow-up for those patients remaining in CR is 24-49 mo (median 39 mo). Life table analysis estimates that 40% (SE 8.3%) of all patients who started induction therapy will remain failure-free at 3 yr. For patients achieving CR, 46% (SE 9%) are projected to remain in both marrow and extramedullary CR at 3 yr. Median failure-free duration was 13 mo, but only 1 patient has relapsed beyond 16 mo. Twenty-nine percent of initial relapses were isolated CNS relapses. The following presenting factors did not relate significantly to outcome: hemoglobin, platelet count, uric acid, race, and mediastinal mass. Age greater than 10 yr was a poor prognosis indicator only in the less than 50,000/microliter WBC group. Sex was not a significant factor after adjusting for WBC. WBC was the most important prognostic factor: 19% (SE 8%) of patients with WBC greater than 50,000/microliter are projected to remain failure- free at 3 yr as compared to 67% (SE 11%) of patients with WBC less than 50,000/microliter. Although the overall results are better than those previously reported for pediatric patients with T-ALL, the long-term failure-free rate remains low for patients presenting with greater than 50,000/microliter WBC.     

The effect of cycling deflection on the injection-molded thermoplastic denture base resins

Objective. The aim of this study was to evaluate the effect of cycling deflection on the flexural behavior of injection-molded thermoplastic resins. Materials and methods. Six injection-molded thermoplastic resins (two polyamides, two polyesters, one polycarbonate, one polymethyl methacrylate) and, as a control, a conventional heat-polymerized denture based polymer of polymethyl methacrylate (PMMA) were used in this study. The cyclic constant magnitude (1.0 mm) of 5000 cycles was applied using a universal testing machine to demonstrate plasticization of the polymer. Loading was carried out in water at 23ºC with eight specimens per group (n = 8). Cycling load (N) and deformation (mm) were measured. Results. Force required to deflect the specimens during the first loading cycle and final loading cycle was statistically significantly different (p < 0.05) with one polyamide based polymer (Valplast) and PMMA based polymers (Acrytone and Acron). The other polyamide based polymer (LucitoneFRS), polyester based polymers (EstheShot and EstheShotBright) and polycarbonate based polymer (ReigningN) did not show significant differences (p > 0.05). None of the materials fractured during the loading test. One polyamide based polymer (Valplast) displayed the highest deformation and PMMA based polymers (Acrytone and Acron) exhibited the second highest deformation among the denture base materials. Conclusion. It can be concluded that there were considerable differences in the flexural behavior of denture base polymers. This may contribute to the fatigue resistance of the materials.     

Detection of circulating crosslinked fibrin derivatives by a heat extraction-SDS gradient gel electrophoretic technique

A technique has been developed to identify and quantitate unique plasmic degradation products of crosslinked fibrin in plasma. In this method, fibrin derivatives are extracted by heat precipitation and dissolved with disulfide bond reduction, after which the crosslinked gamma-gamma chain remnants are identified by SDS-polyacrylamide gradient gel electrophoresis and quantitated by densitometric analysis. A heterogenous group of gamma-gamma chains with molecular weights between 100,000 and 76,000 daltons was identified in lysates of crosslinked fibrin during plasmic degradation in vitro. Three stages of crosslinked fibrin degradation have been arbitrarily defined based primarily on the extent of degradation of these gamma-gamma polypeptide chains. As little as 20 microgram of crosslinked fibrin digests added to 1 ml of normal plasma could be detected by the heat-extraction--gel- electrophoresis technique, identifying the gamma-gamma derivatives with molecular weights of 96,000, 86,000, 82,000, and 76,000 daltons. Plasmic derivatives of gamma-gamma chains were not found in normal plasma, but they were identified in the plasma of patients with disseminated intravascular coagulation and deep-vein thrombosis, both before and in increased quantity during successful thrombolytic therapy.     

Behavior-changing methods for improving adherence to medication

Long-term adherence to antihypertensive drug therapy is poor, and new strategies to predict and improve adherence to prescribed drug regimens are needed. The literature on behavior change is reviewed, and a new perspective on medication adherence is presented. Successfully adopting and continuing with a long-term medication regimen requires behavior change, and behavior change principles can be used to accelerate the adoption of adherence to medicationtaking behavior. The efficacy of behavior-changing interventions, which are tailored to each patient’s stage of change, has been demonstrated in several health behavior areas. Rewards, monitoring devices, and reminder techniques are most useful for individuals in later stages of behavior change, but individuals in earlier stages need consciousnessraising interventions that focus upon awareness of the benefits of therapy. Recent research has yielded reliable ways to measure the stage of change for medication adherence, providing the foundation for the application of behavior-changing principles to the pharmacologic management of hypertension     

Battling insulin resistance in elderly obese people with type 2 diabetes: bring on the heavy weights

Exercise improves insulin resistance and has beneficial effects in preventing and treating type 2 diabetes. However, aerobic exercise is hindered in many type 2 diabetic patients because of advancing age, obesity, and other comorbid conditions. Weight lifting or progressive resistance training (PRT) offers a safe and effective exercise alternative for these people. PRT promotes favorable energy balance and reduced visceral fat deposition through enhanced basal metabolism and activity levels while counteracting age- and disease-related muscle wasting. PRT improves insulin sensitivity and glycemic control; increases muscle mass, strength, and endurance; and has positive effects on bone density, osteoarthritic symptoms, mobility impairment, self-efficacy, hypertension, and lipid profiles. PRT also alleviates symptoms of anxiety, depression, and insomnia in individuals with clinical depression and improves exercise tolerance in individuals with cardiac ischemic disease and congestive heart failure; all of these aspects are relevant to the care of diabetic elders. Moreover, PRT is safe and well accepted in many complex patient populations, including very frail elderly individuals and those with cardiovascular disease. The greater feasibility of using PRT over aerobic exercise in elderly obese type 2 diabetic individuals because of concomitant cardiovascular, arthritic, and other disease provides a solid rationale for investigating the global benefits of PRT in the management of diabetes.     

Randomized trial of proactive rapid genetic counseling versus usual care for newly diagnosed breast cancer patients

Purpose

Breast cancer patients who carry BRCA1/BRCA2 gene mutations may consider bilateral mastectomy. Having bilateral mastectomy at the time of diagnosis not only reduces risk of a contralateral breast cancer, but can eliminate the need for radiation therapy and yield improved reconstruction options. However, most patients do not receive genetic counseling or testing at the time of their diagnosis. In this trial, we tested proactive rapid genetic counseling and testing (RGCT) in newly diagnosed breast cancer patients in order to facilitate pre-surgical genetic counseling and testing.

Methods

We recruited newly diagnosed breast cancer patients at increased risk for carrying a BRCA1/2 mutation. Of 379 eligible patients who completed a baseline survey, 330 agreed to randomization in a 2:1 ratio to RGCT (n?=?220) versus UC (n?=?108). Primary outcomes were genetic counseling and testing uptake and breast cancer surgical decisions.

Results

RGCT led to higher overall (83.8% vs. 54.6%; p?<?0.0001) and pre-surgical (57.8% vs. 38.7%; p?=?0.001) genetic counseling uptake compared to UC. Despite higher rates of genetic counseling, RGCT did not differ from UC in overall (54.1% vs. 49.1%, p?>?0.10) or pre-surgical (30.6% vs. 27.4%, p?>?0.10) receipt of genetic test results nor did they differ in uptake of bilateral mastectomy (26.6% vs. 21.8%, p?>?0.10).

Conclusions

Although RGCT yielded increased genetic counseling participation, this did not result in increased rates of pre-surgical genetic testing or impact surgical decisions. These data suggest that those patients most likely to opt for genetic testing at the time of diagnosis are being effectively identified by their surgeons.

     

Pea chloroplast genes encoding a 4kDa polypeptide of photosystem I and a putative enzyme of C1 metabolism

Summary The nucleotide sequence of 3.2 kbp of pea chloroplast DNA located upstream from the petA gene for cytochrome f, and previously reported to contain the gene for a photosystem I polypeptide, has been determined. Three open reading frames of 587, 40 and 157 codons have been identified. Orf40 encodes a highly conserved, hydrophobic, membrane-spanning polypeptide, and is identified as the gene psaI for the 4 kDa subunit of photosystem I. Orf587 is an extended version of the gene zfpA previously identified as encoding a conserved putative zinc-finger protein. The product of orf587 shows extensive homology to an unidentified open reading frame cotranscribed with a gene for folate metabolism in Escherichia coli and local homology to a region of the subunit of rat mitochondrial propionyl-CoA carboxylase. It is suggested that the product of orf587 is an enzyme of C₁ metabolism and is unlikely to be a regulatory DNA-binding protein. Orf157 potentially encodes an unidentified basic protein, but the protein sequence is not conserved in other plants.     

Inhibition of survivin and aurora B kinase sensitizes mesothelioma cells by enhancing mitotic arrests

PURPOSE: Survivin, a member of the inhibitor of apoptosis gene family, has also been shown to regulate mitosis. It binds Aurora B kinase and the inner centromere protein to form the chromosome passenger complex. Both Aurora B and survivin are overexpressed in many tumors. In this study, we examined whether irradiation affected survivin and Aurora B expression in mesothelioma cells, and how inhibition of these molecules affected radiosensitivity. METHODS AND MATERIALS: ZM447439 and survivin antisense oligonucleotides were used to inhibit survivin and Aurora B kinase respectively. Western blot was performed to determine the expression of survivin, Aurora B, phosphorylated-histone H3 (Ser 10), and caspase cleavage. Multinucleated cells were counted using flow cytometry, and cell survival after treatment was determined using clonogenic assay. RESULTS: At 3-Gy irradiation an increase was observed in levels of survivin and Aurora B as well as the kinase activity of Aurora B, with an increase in G2/M phase. The radiation-induced upregulation of these molecules was effectively attenuated by antisense oligonucleotides against survivin and a small-molecule inhibitor of Aurora B, ZM447439. Dual inhibition of survivin and Aurora B synergistically radiosensitized mesothelioma cells with a dose enhancement ratio of 2.55. This treatment resulted in increased formation of multinucleated cells after irradiation but did not increase levels of cleaved caspase 3. CONCLUSION: Inhibition of survivin and Aurora B induces mitotic cell arrest in mesothelioma cells after irradiation. These two proteins may be potential therapeutic targets for the enhancement of radiotherapy in malignant pleural mesothelioma.