In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.     

Radical radiotherapy for squamous cell carcinoma of the larynx, oropharynx and hypopharynx: patterns of recurrence, treatment and survival

The present study investigates 1085 previously untreated patients with squamous cell carcinoma of the head and neck for factors that influence recurrence following treatment with definitive radiotherapy. In the second part of this study, those diagnosed with recurrence were studied with regard to treatment and were further analysed with regard to identification of prognostic factors which may affect outcome in the patient who actually develops a recurrence.     

Pathways and crossroads to institutional leadership.

When upwardly mobile persons are promoted from lower individual contributor roles to higher, managerial roles, they are confronted by the challenge of negotiating a series of 135-degree "crossroads" or shifts in their careers. Those who make the complete journey must traverse five pathways and four crossroads. These critical career crossroads consist of discontinuous and unprecedented changes in the role responsibilities and account abilities to which managers in transition must respond. At each crossroads, people are confronted by a triple challenge: letting go of anachronistic responsibilities and competencies, preserving those that continue to be useful, and adding new discontinuous responsibilities and consequences. Managers in transition can cope with these demands by making adaptive changes in their preferred activities, behavior patterns, and style. A detailed examination of the unprecedented discontinuities that ambitious, upwardly mobile managers must bridge is presented. The adaptation process that is required at each career crossroads is described, followed by a detailed set of recommended shifts in behavior patterns for the future executive at each crossroads. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A new class of tobacco chitinases homologous to bacterial exo-chitinases displays antifungal activity

A novel chitinase gene of tobacco was isolated and characterized by DNA sequence analysis of a genomic clone and a cDNA clone. Comparative sequence analysis of both clones showed an identity of 94%. The proteins encoded by these sequences do not correspond to any of the previously characterized plant chitinases of classes I-IV and are designated as class V chitinases. Comparison of the chitinase class V peptide sequence with sequences in the Swiss Protein databank revealed significant sequence similarity with bacterial exo-chitinases from Bacillus circulans, Serratia marcescens and Streptomyces plicatus. It was demonstrated that class V chitinase gene expression is induced after treatment of tobacco with different forms of stress, like TMV-infection, ethylene treatment, wounding or ultraviolet irradiation. Two related chitinase class V proteins of 41 and 43 kDa were purified from Samsun NN tobacco leaves inoculated with tobacco mosaic virus. The proteins were purified by Chelating Superose chromatography and gel filtration. In vitro assays demonstrated that class V chitinases have endo-chitinase activity and exhibit antifungal activity toward Trichoderma viride and Alternaria radicina. In addition, it was shown that class V chitinase acts synergistically with tobacco class I beta-1,3-glucanase against Fusarium solani germlings.     

Description and evaluation of a new 3-D computerized treatment planning dose compensator system

Evaluation has been performed of compensators generated by means of a computerized three-dimensional treatment planning system that can utilize either digitized slice profiles or CT scans. Two methods of calculating compensator thickness are used: the modified Batho power law (dSAR) method for digitized profiles and the equivalent TAR (eqTAR) method for CT scans. This system not only compensates for patient surface contours but also compensates for internal inhomogeneities. In addition, any required wedging will be incorporated in the compensator generation. This system has been tested for a number of extreme cases with inhomogeneities and sloping contours. Good agreement was obtained between the measured and computer calculated dose profiles especially along the central axis of the beam. A "Profile Uniformity Index" was defined to quantify the goodness of dose compensation in three dimensions. Compensation using this system can achieve good dose uniformity within the target volume in all clinical cases and is definitely an improvement over systems based solely on tissue deficit.     

Using the Nutrition Screening Initiative to survey the nutritional status of clients participating in a home delivered meals program

A large percentage of older Americans are at risk for malnutrition. This puts them at risk for premature institutionalization, creating a financial burden. The objective of this survey was to determine the nutritional health of clients receiving home delivered meals in Lake County, Indiana and the impact that home delivered meals had on them. Nutrition Screening Initiative (NSI) Determine Your Nutritional Health Checklists were mailed to recipients of meals; 58.3% were returned. Twenty-eight percent were found to be at no nutritional risk, 39% at moderate nutritional risk and 33% at high nutritional risk. One-hundred-thirty clients that scored three or more on the "Checklist" were visited by a Registered Dietitian for further screening using the NSI Level I Screen. This screen found many nutritional problems but the fact that the clients did receive home delivered meals decreased the risk. It was determined by the author that 68% of these clients could not function in their own homes without home delivered meals.     

Differentiation of promonocytic U937 subclones into macrophagelike phenotypes regulates a cellular factor(s) which modulates fusion/entry of macrophagetropic human immunodeficiency virus type 1

Monocytes/macrophages (M/M) and CD4+ T cells are two important targets of human immunodeficiency virus (HIV) infection. Different strains of HIV-1 vary markedly in their abilities to infect cells belonging to the M/M lineage. Macrophagetropic (M-tropic) HIV-1 strains replicate well in primary lymphocytes as well as in primary macrophages; however, they generally infect T-cell lines poorly, if at all. Although promonocytic cell lines such as U937 have been used as in vitro models of HIV-1 infection of M/M, these cell lines are susceptible to certain T-cell-tropic (T-tropic) HIV-1 strains but are resistant to M-tropic HIV-1. In this study, we demonstrate that (i) certain U937 clones ("plus" clones), which are susceptible only to T-tropic HIV-1, become highly susceptible to M-tropic HIV-1 upon differentiation with retinoic acid (RA); (ii) other U937 clones ("minus" clones), which are resistant to both T- and M-tropic HIV-1, remain resistant to both viruses; and (iii) RA treatment induces expression of CCR5, a fusion/entry cofactor for M-tropic HIV-1 in both types of U937 clones, and yet enhances the fusogenicity of the plus clones, but not the minus clones, with M-tropic Env's. These results indicate that the major restriction of M-tropic HIV-1 infection in promonocytic cells occurs at the fusion/entry level, that differentiation into macrophage-like phenotypes renders some of these cells highly susceptible to infection with M-tropic HIV-1, and that CD4 and CCR5 may not be the only determinants of fusion/entry of M-tropic HIV-1 in these cells.     

Refining the level for anticipated hepatotoxicity in acetaminophen poisoning

Treatment of an acetaminophen overdose with N-acetyl cysteine usually is based on the position of the 4-h acetaminophen (APAP) level on the Rumack-Matthew nomogram; however, there is disagreement on the level at which clinically relevant hepatotoxicity occurs. A retrospective review of all acute adult formulation APAP exposures reported to our poison center between 1986 and 1993 was performed and cases corresponding to the "possible risk or toxicity" range on the nomogram were identified. Our current poison center protocol for APAP poisoning does not recommend treatment with N-acetylcysteine (NAC) in low-risk patients if the 4-h serum APAP level or the extrapolated equivalent falls within the possible toxicity range on the nomogram. Seventeen cases met the inclusion criteria for the study and received no NAC; six additional patients met inclusion criteria but received one or two doses of NAC before therapy was discontinued. No patients in either group demonstrated clinical evidence of hepatotoxicity. This pilot study suggests that patients with no risk factors and APAP levels in the "possible risk" range may not require NAC therapy.     

Hamstrings and psoas lengths during normal and crouch gait: implications for muscle-tendon surgery

OBJECTIVE: To study the relative contribution of the lung and the chest wall on the total respiratory system mechanics, gas exchange, and work of breathing in sedated-paralyzed normal subjects and morbidly obese patients, in the postoperative period. SETTING: Policlinico Hospital, University of Milan, Italy. METHODS: In ten normal subjects (normal) and ten morbidly obese patients (obese), we partitioned the total respiratory mechanics (rs) into its lung (L) and chest wall (w) components using the esophageal balloon technique together with airway occlusion technique, during constant flow inflation. We measured, after abdominal surgery, static respiratory system compliance (Cst,rs), lung compliance (Cst,L), chest wall compliance (Cst,w), total lung (Rmax,L) and chest wall (Rmax,w) resistance. Rmax,L includes airway (Rmin,L) and "additional" lung resistance (DR,L). DR,L represents the component due to viscoelastic phenomena of the lung tissue and time constant inequalities (pendelluft). Functional residual capacity (FRC) was measured by helium dilution technique. RESULTS: We found that morbidly obese patients compared with normal subjects are characterized by the following: (1) reduced Cst,rs (p < 0.01), due to lower Cst,L (55.3 +/- 15.3 mL x cm H2O-1 vs 106.6 +/- 31.7 mL x cm H2O-1; p < 0.01) and Cst,w (112.4 +/- 47.4 mL x cm H2O-1 vs 190.7 +/- 45.1 mL x cm H2O-1; p < 0.01); (2) increased Rmin,L (4.7 +/- 3.1 mL x cm H2O x L-1 x s; vs 1.0 +/- 0.8 mL x cm H2O x L-1 x s; p < 0.01) and DR,L (4.9 +/- 2.6 mL x cm H2O x L-1 x s; vs 1.5 +/- 0.8 mL x cm H2O x L-1 x s; p < 0.01); (3) reduced FRC (0.665 +/- 0.191 L vs 1.691 +/- 0.325 L; p < 0.01); (4) increased work performed to inflate both the lung (0.91 +/- 0.25 J/L vs 0.34 +/- 0.08 J/L; p < 0.01) and the chest wall (0.39 +/- 0.13 J/L vs 0.18 +/- 0.04 J/L; p < 0.01); and (5) a reduced pulmonary oxygenation index (PaO2/PAO2 ratio). CONCLUSION: Sedated-paralyzed morbidly obese patients, compared with normal subjects, are characterized by marked derangements in lung and chest wall mechanics and reduced lung volume after abdominal surgery. These alterations may account for impaired arterial oxygenation in the postoperative period.