A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111

Recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) shortens the time to neutrophil recovery after intensive chemotherapy, but its role in the treatment of adults with acute lymphoblastic leukemia (ALL) is uncertain. We randomly assigned 198 adults with untreated ALL (median age, 35 years; range, 16 to 83) to receive either placebo or G-CSF (5 microgram/kg/d) subcutaneously, beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was >/=1, 000/microL for 2 days. The study assignment was unblinded as individual patients achieved a complete remission (CR). Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy. Patients assigned to placebo received no further study drug. The median time to recover neutrophils >/=1,000/microL during the remission induction course was 16 days (interquartile range [IQR], 15 to 18 days) for the patients assigned to receive G-CSF and 22 days (IQR, 19 to 29 days) for the patients assigned to placebo (P < .001). Patients in the G-CSF group had significantly shorter durations of neutropenia (<1, 000/microL) and thrombocytopenia (<50,000/microL) and fewer days in the hospital (median, 22 days v 28 days; P = .02) compared with patients receiving placebo. The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo (P = .04 by the chi-square test for trend). During Courses IIA and IIB of consolidation treatment, patients in the G-CSF group had significantly more rapid recovery of neutrophils >/=1,000/microL than did the control group by approximately 6 to 9 days. However, the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group. Overall toxicity was not lessened by the use of G-CSF. After a median follow-up of 4. 7 years, there were no significant differences in either the disease-free survival (P = .53) or the overall survival (P = .25) for the patients assigned to G-CSF (medians, 2.3 years and 2.4 years, respectively) compared with those assigned to placebo (medians, 1.7 and 1.8 years, respectively). Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment, but its use did not markedly affect the ultimate outcome.     

Effects of cold stress on survival and reproduction of Haematobia irritans (Diptera: Muscidae)

1. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) increases the stability of the oxazolidine prodrug toward hydrolysis. 2. The binding constant (Kb) and rate constant (Kc) for the hydrolysis of the prodrug-HP-beta-CD complex were calculated from the kinetic data. 3. Ion-spray mass spectra confirmed prodrug-HP-beta-CD complexation. 4. Mass spectral and kinetic data indicated 1:1 stoichiometry for the complex. 5. A significant elevation of locomotor activity in rats was observed when either (-)-ephedrine or the prodrug was administered by either the intraperitoneal or the oral route. 6. Addition of HP-beta-CD potentiated the central nervous system effect of both (-)-ephedrine and the prodrug when administered intraperitoneally. However, when the drugs were administered orally, HP-beta-CD caused a decrease in activity.     

Hereditary neurocutaneous angiomatosis. Report of four cases

The authors report the coexistence of vascular nevi (hemangiomas and arteriovenous malformations (AVMs) of the skin) with AVMs and venous malformations of the brain in male siblings from two related but nonconsanguineous families of three generations. The proband, his siblings, parents, aunts, uncles, and cousins were examined, underwent magnetic resonance (MR) imaging and MR angiography, and when appropriate, cerebral angiography. A father had vascular nevi and a mother, his sister, had an azygos anterior cerebral artery. No other cutaneous or cerebrovascular malformations were present in the parents. Each of the two families had two boys and one girl, 9 to 18 years of age. All the children had vascular nevi and all of the boys had coexisting cerebrovascular malformations: AVMs in three, and a venous malformation in another. One boy had three cerebral AVMs. Two boys had a cerebral hemorrhage, and one also had focal motor seizures. The skin lesions were not those of the Sturge-Weber-Dimitri, Rendu-Osler-Weber, or Wybum-Mason syndromes. The association of cutaneous and cerebrovascular malformations was seen only in males in these families. but females have also been reported in the literature. The results obtained in these families and three other families reported from Western and Central Europe indicate that the association of cerebral and cutaneous vascular hamartomas constitutes a distinct, hereditary clinicopathological entity with autosomal dominant inheritance and variable penetrance. The clinical manifestations of this syndrome are visible, painful vascular nevi, epilepsy, cerebral hemorrhage, and focal neurological deficits. The preponderance of male patients with the full expression of the syndrome suggests a possible hormonal influence on the expression of the gene.     

X-ray microtomography (microCT) of the progression of sulfate attack of cement paste

High-resolution X-ray computed tomography (i.e., microCT or microtomography) was used to study the sulfate attack of cylinders of Type I cement paste cast with water-cement (w/c) ratios of 0.45, 0.50 and 0.60. Damage levels in samples exposed to a Na₂SO₄ solution with 10,000 ppm sulfate ion concentration were qualitatively rated from 0 (no damage) to 4 (extreme damage) based upon visual examination of the samples' exteriors and microtomography of the samples' interiors. The greater the w/c ratio, the more rapid the onset of sulfate damage. The corners of the cylinders appeared to be particularly susceptible to spalling, and damage may have continued into the cement paste by formation of subsurface cracks.     

The lead dioxide electrode

The recent literature dealing with the redox mechanism of the lead-acid cell positive electrode is reviewed. The basis electrochemistry of lead dioxide in its various polymorphic modifications and states of subdivision is considered in relation to the important aspects of electrode technology of which the major industrial application of the material is the conventional lead-acid cell. The proposed mechanism of the reduction (discharge) of lead dioxide in various acidic solutions are considered in relation to the present state of electrode kinetic theory. The reverse reaction by which lead dioxide is formed and the parasitic intrusion of the self discharge are dealt with as a precursor to the total cyclic process. It is concluded that in a number of respects the mechanisms proposed do not adequately represent the totality of the experimental observations. Such shortcomings are emphasized and extensions to present research are proposed.     

Coupling of dry matter and nitrogen accumulation in ryegrass

The logistic model has proven very useful in relating dry matter production of warm season perennial forage grasses to applied nitrogen. A recent extension of the model coupled dry matter and plant N accumulation through a common response coefficient c. The objective of this analysis was to apply the extended logistic model to cool season Gulf annual ryegrass (Lolium multiflorum Lam.) and to establish a common response coefficient c between accumulation of dry matter and plant N. Analysis of variance established the validity of this hypothesis. The model accurately described response of dry matter, plant N removal, and plant N concentration to applied N, with an overall correlation coefficient of 0.9954. Furthermore, the model closely described the relationship between yield and plant N removal, as well as between plant N concentration and plant N removal. The logistic equation is well-behaved and simple to use on a pocket calculator. It can be used to estimate yields and plant N removal in evaluation of agricultural production and environmental quality.     

Creep and Creep Fracture in Hot-Pressed Alumina

The creep and creep fracture behavior of two hot-pressed aluminas are presented, for both flexural and tensile testing. Steady-state power-law creep is observed with a stress exponent of about 2 for each material. Three distinct fracture regimes are found. At high stress in flexure, fracture occurs by slow crack growth with a high stress dependence of the failure time. At intermediate stresses, in both flexure and tension, creep fracture occurs by multiple microcracking after modest strains. Failure times exhibit a modest stress dependence (stress exponent of 2.5 in tension and 3 in flexure), with a constant failure strain equal to 0.09. The failure times are considerably longer in flexure than in tension, because of the constraint imposed on crack growth by the bending geometry. We conclude that flexure cannot be used for creep lifetime assessment, even in simple, single-phase materials such as Al₂O₃. At low stresses, in tension, failure also exhibits a modest stress dependence but with a much higher failure strain. The material shows the onset of super-plastic behavior.     

Hydrogenation of 3,4-epoxy-1-butene over Cu–Pd/SiO2 catalysts prepared by electroless deposition

Electroless deposition has been used to prepare Cu–Pd/SiO₂ bimetallic catalysts wherein initial Cu coverages are limited only to the pre-existing Pd surface. Cu loading on the Pd surface can be systematically varied by modification of deposition kinetic parameters. In this case deposition time was used as the kinetic variable for the preparation of a series of Cu–Pd catalysts. These materials have been characterized using atomic absorption, CO chemisorption, and FT-IR (adsorption of CO), and then evaluated for the hydrogenation of 3,4-epoxy-1-butene, a functionalized olefin having many potential reaction pathways. Catalyst performance and characterization results suggest that Cu is not distributed in a monodisperse manner on the Pd surface, indicating the existence of autocatalytic deposition of Cu on Cu sites. The FT-IR results suggest that although CO adsorption on all sites is suppressed by Cu addition, initial Cu deposition occurs more readily on certain sites. The bimetallic Cu–Pd sites that are formed exhibit unusually high activity for EpB conversion and formation of unsaturated alcohols and aldehydes. This bimetallic effect on catalyst activity and selectivity is best explained, not by the existence of either ligand or ensemble effects, but rather by the bifunctional nature of the Cu–Pd sites present on the surface of these catalysts.     

A dislocation model for the two critical stress intensities required for threshold fatigue crack propagation

We have examined the variations, with decreasing load ratio, of threshold peak and cyclic stress intensities required for fatigue crack growth in stage I (mainly mode II loading) using a simple model simulating dislocation motion near a crack tip. In this model the crack grows by dislocations running into the crack during loading and unloading phases. Initially we have studied the behaviour of a crack with a dislocation source relatively far away from the crack tip. Crack propagation rates showed a Paris regime at high ΔK, and an abrupt threshold value ΔK_th below which no crack growth occurred. The variation with load ratio of the peak (K_th) and cyclic (ΔK_th) stress intensities at the fatigue threshold showed that two different processes controlled the behaviour. At high load ratios dislocations are generated readily during loading and the threshold is controlled by the need for sufficient unloading to allow dislocations to run back into the crack, so that the criterion ΔK ≥ ΔK∗ results. At negative load ratios it is the generation of dislocations during the loading phase that controls the threshold condition, since once generated, the large unloading and reversed loading easily forces dislocations back to the crack. Under these conditions the threshold criterion becomes K_max ≥ K∗.     

Development of an operational fitness test for the Royal Air Force

Since 2002, the Royal Air Force (RAF) has been working towards developing role-related physical tests for use as an operational fitness test (OFT). The purpose of this study was to establish reliability of the OFT (comprising four tests), investigate gym-based tests as predictors of performance and establish performance standards. Fifty-eight RAF personnel performed the OFT on three occasions. A separate cohort carried out fitness and anthropometric tests before performing the OFT, by way of establishing performance predictors. Documented evidence and views of an expert panel were used to determine OFT standards. Reliability ranged from moderate to good for three tests, with one test (Dig) showing poor reliability. The 95% limits of agreement for the prediction models ranged from good to poor (6.7-34.2%). The prediction models were not sufficiently accurate to estimate confidently OFT performance, but could be used as a guide to quantify likely outcome and training needs.