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.     

Noninvasive measurement of distal radius instability

Except for subjective clinical criteria, there is no formal definition of distal radius fracture instability in the literature. The purposes of this ex vivo biomechanical study were (1) to provide an objective mechanical definition of fracture instability and (2) to demonstrate a noninvasive method that allows for direct measurement of instability. The following 3 questions are addressed: (1) Can the stability of distal radius fractures be measured using computed tomography (CT)? (2) Are the stability measurements reproducible? (3) How does external fixation change stability? A CT technique is described that was used to measure displacement of fracture fragments and measure the compliance of ex vivo distal radius fractures before and after external fixation. Validation studies of the CT technique revealed a mean coefficient of variation of 0.38. There was a linear relationship between measured and known displacements for all 3 orthogonal planes (coefficient of determination 0.99; p < .01). There was significant fracture displacement with loads as small as 20 N. The slope of the load-displacement curve (structural compliance) provided a quantitative measure of fracture instability. Fracture compliance decreased up to 69% after application of an external fixator.     

Aortopulmonary fistula in an infected Dacron graft for coarctation of the aorta: an uncommon cause of hemoptysis

Hemoptysis secondary to an aortobronchial fistula is rare and uniformly fatal when left untreated. The authors describe a case of massive hemoptysis caused by an aortopulmonary fistula in an infected Dacron graft used successfully to repair a coarctation of the aorta.     

Langerhans cell density in normal human oral mucosa and skin: relationship to age, smoking and alcohol consumption

Hyperthyroidism is a common endocrinologic disorder affecting many organ systems. Musculoskeletal and neurological involvement present themselves as fatigue, muscle weakness and paralysis. Electromyography (EMG) is essential for differential diagnosis of muscle weakness. Well defined neuropathy and myopathy have been described in these patients. In the present study 17 hyperthyroid patients were evaluated with electrophysiological tests in addition to physical and neurological examinations and biochemical laboratory studies. Needle EMG, motor and sensory conduction velocities, median and tibial somatosensory evoked potentials (SEP) were studied. For assessment of the activity of disease clinical status, neurological symptom and disability scores and serum T3, T4 and TSH levels were examined. Statistical analysis of neuroelectrophysiological findings of the patient and the control groups yielded meaningful difference in the needle EMG, sensory conduction velocity and evoked potential findings. Abnormalities were observed in 80% of the proximal muscles besides polyphasic potentials that were seen in 20% of the extensor digitorum brevis muscle. Median, ulnar and sural nerve sensory action potential amplitudes were found to be lower than that of the control group. Sural sensory nerve conduction velocity of patients was decreased in 35.5%, prolongation of median SEP latencies and increase in the amplitudes were not however statistically significant. Prolongation of Tibial SEP N1, P2 latencies were seen in 47%, amplitudes of N1 were increased in 88.2%, P2 in 58.8%, N2 in 47%. The thyroid clinical status score was correlated with Tibial SEPs amplitude. These findings suggest the presence of an initial axonal type of mild polyneuropathy. As a conclusion electrophysiological studies can be useful in the diagnosis of asymptomatic polyneuropathy in hyperthyroid patients.     

GCase and LIMP2 Abnormalities in the Liver of Niemann Pick Type C Mice

The lysosomal storage disease Niemann–Pick type C (NPC) is caused by impaired cholesterol efflux from lysosomes, which is accompanied by secondary lysosomal accumulation of sphingomyelin and glucosylceramide (GlcCer). Similar to Gaucher disease (GD), patients deficient in glucocerebrosidase (GCase) degrading GlcCer, NPC patients show an elevated glucosylsphingosine and glucosylated cholesterol. In livers of mice lacking the lysosomal cholesterol efflux transporter NPC1, we investigated the expression of established biomarkers of lipid-laden macrophages of GD patients, their GCase status, and content on the cytosol facing glucosylceramidase GBA2 and lysosomal integral membrane protein type B (LIMP2), a transporter of newly formed GCase to lysosomes. Livers of 80-week-old Npc1^−/− mice showed a partially reduced GCase protein and enzymatic activity. In contrast, GBA2 levels tended to be reciprocally increased with the GCase deficiency. In Npc1^−/− liver, increased expression of lysosomal enzymes (cathepsin D, acid ceramidase) was observed as well as increased markers of lipid-stressed macrophages (GPNMB and galectin-3). Immunohistochemistry showed that the latter markers are expressed by lipid laden Kupffer cells. Earlier reported increase of LIMP2 in Npc1^−/− liver was confirmed. Unexpectedly, immunohistochemistry showed that LIMP2 is particularly overexpressed in the hepatocytes of the Npc1^−/− liver. LIMP2 in these hepatocytes seems not to only localize to (endo)lysosomes. The recent recognition that LIMP2 harbors a cholesterol channel prompts the speculation that LIMP2 in Npc1^−/− hepatocytes might mediate export of cholesterol into the bile and thus protects the hepatocytes.     

Effect of high temperature heat treatment on intergranular corrosion of AlMgSi(Cu) model alloy

Copper containing 6000-series aluminium alloys may become susceptible to intergranular corrosion (IGC) as a result of improper thermomechanical processing. Effect of cooling rate after solution heat treatment on the corrosion behaviour of a model AlMgSi(Cu) alloy of nominal composition (wt%) 0.6 Mg, 0.6 Si, 0.2 Fe, 0.2 Mn and 0.1 Cu was investigated. Slow cooling rates were simulated by isothermal treatment for predetermined times in lower temperature baths immediately after solution heat treatment. Treatment for 10-100 s at temperatures below 400 °C introduced susceptibility to IGC. Longer heat treatment at the same temperatures introduced susceptibility to pitting. A corrosion resistant time zone was found between the zones of IGC and pitting at temperatures lower than 350 °C. Quenching in water after solution heat treatment prevented IGC. IGC was related to microgalvanic coupling between the noble Q-phase (Al₄Mg₈Si₇Cu₂) grain boundary precipitates and the adjacent depleted zone. Pitting was attributed to coarse particles in the matrix. Possible mechanisms causing the corrosion resistant intermediate zone are discussed. The results indicate possible methods for obtaining increased corrosion resistance of similar alloys by proper thermal processing.     

Biomimetic Polymer Nanostructures by Injection Molding

The nanometer scale topography of self‐assembling structural protein complexes in animals is believed to induce favorable cell responses. An important example of such nanostructured biological complexes is fibrillar collagen that possesses a cross‐striation structure with a periodicity of 69 nm and a peak‐to‐valley distance of 4–6 nm. Bovine collagen type I was assembled into fibrillar structures in vitro and sedimented onto solid supports. Their structural motif was transferred into a nickel replica by physical vapor deposition of a small‐grained metal layer followed by galvanic plating. The resulting inverted nickel structure was found to faithfully present most of the micrometer and nanometer scale topography of the biological original. This nickel replica was used as a die for the injection molding of a range of different thermoplastic polymers. Total injection molding cycle times were in the range of 30–45 seconds. One of the polymer materials investigated, polyethylene, displayed poor replication of the biological nanotopographical motif. However, the majority of the polymers showed very high replication fidelity as witnessed by their ability to replicate the cross‐striation features of less than 5 nm height difference. The latter group of materials includes poly(propylene), poly(methyl methacrylate), poly(L ‐lactic acid), polycaprolactone, and a copolymer of cyclic and linear olefins (COC). This work suggests that the current limiting factor for the injection molding of nanometer scale topography in thermoplastic polymers lies with the grain size of the initial metal coating of the mold rather than the polymers themselves.

     

Nitrogen transformations during hydrolysis and nitrification of urea

Nitrogen transformations occurring in ten soils fertilized with urea were determined during incubation in the laboratory for four weeks. Urea was applied at one rate, but with different placement methods. Urea was applied in solution, as prills with a 1 cm grid spacing and as prills with no spacing. Unfertilized soils and soils amended with KNO₃ solution were included as controls.Nitrite accumulated in the majority of soils treated with urea, and the maximum nitrite concentration measured was directly related to initial soil pH. Cumulative gaseous N losses as percentages of applied N were: NH₃, 0-59.6; N₂, 0-4.9; N₂O, 0-9.9; KMnO₄-N, 0-1.3; CH₃ONO, 0-<0.1. No gaseous N evolution was detected in control treatments. Gaseous N losses were correlated with soil pH (NH₃) maximum NO ₂ ^- concentration (N₂, N₂O, KMnO₄-N) and organic C content (N₂, N₂O). Fertilizer placement effects were generally not significant and were small in comparison with differences between soils.

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Resumo Foram determinadas, durante incubação em laboratório por quatro semanas, as transformações do nitrogênio ocorridas em dez solos fertilizados com uréia. A uréia foi aplicada a um só nivel, mas com diferentes métodos de aplicação: em solução e em grânulos com 1 cm de espaçamento de grade e em grânulos sem espaçamento. Solos não fertilizados e solos corrigidos com solução de KNO₃ foram incluidos como controles.O nitrito acumulado na maioria dos solos tratados com uréia e a concentração máxima de nitrito medido foram diretamente relacionados ao pH inicial do solo. As perdas cumulativas de N gasoso tomadas em percentagens de N aplicado foram: NH₃, 0-59.6; N₂, 0-4.9; N₂O; 0-9.9; KMnO₄-N, 0-1.3; CH₃ONO, 0-<0.1. Não foi detectada liberação de N gasoso nos tratamentos de controle. As perdas de N gasoso foram relacionadas com o pH do solo (NH₃), concentração máxima de NO ₂ ^- (N₂, N₂O, KMnO₄-N) e teor de C orgânico (N₂, N₂O). Efeitos da aplicação de fertilizante não foram de um modo geral significativos e foram pequenos em comparação com as diferenças entre os solos.