Limited Margins Using Modern Radiotherapy Techniques Does Not Increase Marginal Failure Rate of Glioblastoma

PURPOSE: We investigate the patterns of failure in the treatment of glioblastoma(GBM) based on clinical target volume(CTV) margin size,dose delivered to the site of initial failure,and the use of temozolomide and intensity-modulated radiotherapy(IMRT).METHODS: Between August 2000 and May 2010,161 patients with GBM were treated with radiotherapy with or without concurrent temozolomide.Patients were treated with CTV expansions that ranged from 5 to 20 mm using a shrinking field technique.Patterns of failure and time to progression and overall survival were compared based on CTV margin,use of temozolomide,and use of IMRT.Kaplan Meier analysis was used to estimate survival times,and χ test was used for comparison of cohorts.RESULTS: For patients treated with 5-,10-,and 15-to 20-mm CTV,79%,77%,and 86% experienced failures in the 60 Gy volume,respectively.Forty-eight percent,55%,and 66% of patients with 5-,10-,and 15-to 20-mm CTV experienced failures in the 46 Gy volume,respectively.There was no statistical difference between patients treated with 5-,10-,15-to 20-mm margins with regard to 60 Gy failure(P=0.76),46 Gy failure(P=0.51),or marginal failure(P=0.73).Eighty percent of patients receiving temozolomide experienced failures in the 60 Gy volume.There was no increased likelihood of marginal failures in patients receiving IMRT(P =0.97).CONCLUSIONS: Modern treatment techniques including use of concurrent temozolmide,limited CTV margin size,and IMRT have not greatly changed the patterns of failure of GBM.     

Prevalence and classification of HIV-associated oral lesions

OBJECTIVES: An International Workshop addressed the prevalence and classification of HIV/AIDS associated oral lesions.
DESIGN: Five questions provided the framework for discussion and literature review. What is the prevalence of oral lesions in children and adults? Should the accepted classification of HIV-related oral lesions be modified in the light of recent findings? Why is there a gender difference in the prevalence of oral lesions in developed and developing countries? Are there unusual lesions present in developing countries? Is there any association between modes of transmission and the prevalence of oral lesions?
RESULTS: Workshop discussion emphasized the urgent need for assistance in the development of expertise to obtain accurate global prevalence data for HIV-associated oral lesions. Oral candidiasis has been consistently reported as the most prevalent HIV-associated oral lesion in all ages. Penicilliosis marneffei, a newly described fungal infection, has emerged in South-east Asia. Oral hairy leukoplakia and Kaposi's sarcoma appear to be associated with male gender and male-to-male HIV transmission risk behaviours. These lesions occur only rarely in children.
CONCLUSIONS: Additional prevalence data are needed from developing countries prior to substantially altering the 1993 ECC/WHO Classification of oral lesions associated with adult HIV infection. The workshop confirmed current oral disease diagnostic criteria.     

L-精氨酸对糖尿病大鼠心肌缺血再灌注损伤的影响

目的:观察糖尿病大鼠心肌缺血再灌注时血管紧张素Ⅱ、胰岛素样生长因子1、醛固酮、细胞间黏附分子1和自由基代谢的变化及L-精氨酸对其的影响。方法:实验于2005-02/2006-06在江苏大学医学院机能学实验室完成。①实验分组:腹腔注射链脲佐菌素制作糖尿病大鼠模型,30只大鼠造模成功。按随机数字表法分为3组(n=10):心肌缺血再灌注组:开胸结扎冠脉,造成心肌缺血,60min后放松再灌注60min;L-精氨酸治疗组:于手术前4周灌胃L-精氨酸250mg/(kg·d),然后重复心肌缺血再灌注组操作;假手术组:完成操作后只穿线不结扎,观察2h作为对照。实验结束时心室取血6mL,摘取心脏,留取左心室心肌组织。②实验评估:检测大鼠血浆血管紧张素Ⅱ、醛固酮和血清胰岛素样生长因子1含量及心肌细胞间黏附分子1蛋白表达。检测大鼠血清、心肌组织超氧化物歧化酶、谷胱甘肽-过氧化物酶活性、丙二醛含量及心肌线粒体Na ,K -ATP酶、Mg2 -ATP酶、Ca2 -ATP酶活性。结果:30只大鼠全部进入结果分析。①与假手术组相比,心肌缺血再灌注组血浆血管紧张素Ⅱ、醛固酮含量明显升高(P<0.05～0.01),血清胰岛素样生长因子1含量降低(P<0.05);L-精氨酸治疗4周后血浆血管紧张素Ⅱ、醛固酮含量低于心肌缺血再灌注组(P<0.05～0.01),血清胰岛素样生长因子1含量高于心肌缺血再灌注组(P<0.05)。②与假手术组相比,心肌缺血再灌注组血清、心肌丙二醛含量明显升高(P<0.05),血清、心肌超氧化物歧化酶和谷胱甘肽-过氧化物酶活性明显降低(P<0.05￣0.01);用L-精氨酸治疗4周后血清、心肌丙二醛含量低于心肌缺血再灌注组(P<0.05￣0.01),血清、心肌超氧化物歧化酶和谷胱甘肽-过氧化物酶活性高于心肌缺血再灌注组(P<0.05～0.01)。③与假手术组相比,心肌缺血再灌注组心肌线粒体Na ,K -ATP酶、Mg2 -ATP酶、Ca2 -ATP酶活性明显降低(P<0.05),心肌细胞间黏附分子1蛋白表达明显升高(P<0.01);用L-精氨酸治疗4周后心肌线粒体Na ,K -ATP酶、Mg2 -ATP酶、Ca2 -ATP酶活性明显高于心肌缺血再灌注组(P<0.05),心肌细胞间黏附分子1蛋白表达低于心肌缺血再灌注组(P<0.05)。结论:血管紧张素Ⅱ、醛固酮和胰岛素样生长因子1可能共同参与了糖尿病心肌缺血再灌注的发生,细胞间黏附分子1蛋白表达与糖尿病心肌损伤关系密切。L-精氨酸通过减少细胞间黏附分子1蛋白表达,起心肌保护作用。糖尿病心肌缺血再灌注时存在自由基代谢异常,补充L-精氨酸后,可通过提高超氧化物歧化酶、谷胱甘肽-过氧化物酶和ATP酶活性,降低丙二醛水平,减轻自由基损伤,改善心肌组织功能。     

A nutrient relay sustains subtropical ocean productivity

The expansive gyres of the subtropical ocean account for a significant fraction of global organic carbon export from the upper ocean. In the gyre interior, vertical mixing and the heaving of nutrient-rich waters into the euphotic layer sustain local productivity, in turn depleting the layers below. However, the nutrient pathways by which these subeuphotic layers are themselves replenished remain unclear. Using a global, eddy-permitting simulation of ocean physics and biogeochemistry, we quantify nutrient resupply mechanisms along and across density surfaces, including the contribution of eddy-scale motions that are challenging to observe. We find that mesoscale eddies (10 to 100 km) flux nutrients from the shallow flanks of the gyre into the recirculating interior, through time-varying motions along density surfaces. The subeuphotic layers are ultimately replenished in approximately equal contributions by this mesoscale eddy transport and the remineralization of sinking particles. The mesoscale eddy resupply is most important in the lower thermocline for the whole subtropical region but is dominant at all depths within the gyre interior. Subtropical gyre productivity may therefore be sustained by a nutrient relay, where the lateral transport resupplies nutrients to the thermocline and allows vertical exchanges to maintain surface biological production and carbon export.

The sinking of particulate organic carbon from the sunlit euphotic zone into the deeper, dark ocean maintains an oceanic reservoir of dissolved inorganic carbon, changes in which can significantly modify atmospheric CO₂ (1). The ocean’s subtropical gyres exhibit low surface concentrations of nutrients and biomass but, due to their very large surface area, may contribute a significant fraction of global export. For example, the North Pacific subtropical gyre is estimated to represent ~20 to 50% of the total North Pacific organic sinking flux (2, 3). The wind forcing over the subtropical basins leads to a downward doming of the density surfaces that contain an extensive volume of low-nutrient waters (4), as revealed in an observed transect from the North Pacific (Fig. 1) (5). The mode of nutrient resupply and the long-term maintenance of biological productivity in subtropical gyres have presented a conundrum for several decades. Inorganic nutrients are incorporated into photosynthetic phytoplankton and pass through the food web, but despite efficient recycling within the sunlit euphotic zone (6, 7), gravitational sinking and the subduction of organic matter deplete the surface nutrients of the subtropical gyres. These surface nutrient losses are largely viewed as being offset by the physical transport of nutrient-enriched, deeper waters back into the sunlit zone, together with smaller contributions from atmospheric deposition and nitrogen fixation. However, the nature of the nutrient pathways recharging the subtropical nutrient reservoir below the euphotic zone remains poorly constrained.Open in a separate windowFig. 1.PO43− concentration (μmol kg⁻¹) in the North Pacific basin obtained from the Global Ocean Data Analysis Project (GLODAP) V2.2 atlas and plotted using Data-Interpolating Variational Analysis (DIVA) gridding in Ocean Data View. (A) Transect along 155 ^∘W, with contours of constant density σ_o (thick dashed lines) and sampling locations (gray points). The solid black line indicates the σ_o = 26.0 surface. (B) PO43− distribution along σ_o = 26.0 with sampling locations indicated by gray points.The sharp vertical gradient of nutrients just below the euphotic layer can sustain the vertical supply of nutrients up to the surface. Transfer of nutrients upward into the subtropical euphotic zone has been attributed to vertical diapycnal mixing (8–11); the passage of mesoscale eddies, which adiabatically lift nutrient-rich, subeuphotic layers into the light (12–19); and submesoscale (1 to 10 km) features that are associated with strong vertical circulations (20–24). However, all of these localized processes deliver nutrients into the euphotic layer while depleting the subeuphotic layers below (17, 25). A long-standing question is how the nutrient inventory of this subeuphotic layer, which fuels the local vertical supplies, is maintained over the longer term (26, 27).At the flanks of the subtropical gyre, wind-driven upwelling brings nutrient-rich waters toward the surface, forming nutrient gradients in the subpolar and equatorial regions, as seen in observed transects (Fig. 1A). Within the frictional boundary layer of the ocean, the wind-driven, meridional Ekman transport acts on these lateral gradients to transfer nutrients into the subtropical gyre, significantly supplementing vertical processes in sustaining local productivity (4, 28, 29). However, this lateral transport contribution is confined to the upper few tens of meters and diminishes away from the gyre margins due to biological consumption (4).Mesoscale eddies can provide a lateral transport of nutrients, which involves both stirring and advective transfer along density surfaces (11, 17, 25, 30, 31). Idealized simulations and theory suggest an important combined nutrient supply to the gyre from lateral eddy diffusion and Ekman transport (30). Diagnostics of a more realistic, global eddy-resolving model show that lateral eddy transfers do provide an important nutrient flux across the boundaries of the subtropical gyre (31). Stimulated by these model-based inferences, an observational field study, measuring microscale turbulence and nutrients, reveal signals of eddy stirring along density surfaces, providing a weak nutrient supply within the thermocline over the center of the North Atlantic subtropical gyre (11). A closure for the nutrient supply then suggests that the nutrient delivery by mesoscale eddy stirring should be one to two orders of magnitude larger over the flanks of the subtropical gyre due to an increase in nutrient gradients and a greater tilt of the density surfaces (11). These enhanced nutrient gradients and isopycnal slopes are evident near the margins of the subtropical gyre, particularly at its southern flank, between σ₀ = 24.0 and 26.5 (Fig. 1). An eddying numerical simulation reveals the associated mesoscale flux of nutrients, visible as streamers of high-phosphate waters emanating from nutrient-rich currents all around the margins of the subtropical gyre (Fig. 2A and Movie S1).Open in a separate windowFig. 2.Snapshot of simulated PO43− concentration (mmol m⁻³) during the month of September and along the σ₀ = 26.0 isopycnal (A) over the north subtropical Pacific basin and (B) in the proximity of the Hawaiian islands. The black line contours in B depict the depth of the isopycnal surface with 10-m contour intervals. Mesoscale features transport nutrients into the North Pacific subtropical gyre through the combined action of eddy stirring that draws out filaments of tracer and advection by coherent eddy structures.In this study, we quantify the nutrient pathways and fluxes of the subtropical North Pacific Ocean, in the context of a global eddy-permitting numerical model with explicit representation of biogeochemical and ecological processes (Materials and Methods). In doing so, we test and illustrate the hypothesis of ref. 11 that the lateral eddy transfer contribution is stronger at the gyre margins and in the thermocline. Complementing previous work (31), we resolve along- and across-density surface fluxes and the depth and intragyre structures in fluxes and balances, as well as the contribution of dissolved organics.We find that a nutrient relay occurs in the subtropical gyre (11), involving the eddying transfer of nutrients from the upwelling flanks of the gyre, downward along sloping isopycnals into the subtropical gyre interior. This nutrient supply into the thermocline offsets the export of organic matter to the deep ocean and fuels upward vertical transfer to the surface, helping to sustain biological production in the euphotic layer. We illustrate this nutrient relay in the following, detailed analysis of the nutrient budget for density layers over the North Pacific subtropical gyre.     

A prospective study of blood donations in healthy elderly persons

Iron stores were observed in 57 healthy elderly volunteers, between 63 and 77 years of age, who donated 5 units of blood over approximately 1 year. An equal number of nondonors who contributed approximately 7 mL of blood at each visit for iron status measurements only were seen at the same frequency as the donor population. At entrance to the study, iron stores in women and men averaged 724 and 875 mg, respectively. After five donations, mean iron stores dropped to 67 mg in women (n = 27) and 362 mg in men (n = 30); four women (15%) became iron deficient, while two (7%) developed iron deficiency anemia. Three men (10%) developed iron deficiency, but none were found to be anemic. Mean intakes of iron were 23.3 and 22.5 mg per day, respectively, for women and men. Iron intakes were adequate to meet iron requirements of nondonors, but they were not sufficient to halt the steady decrease in iron stores among the donor population, in whom iron absorption increased from approximately 5 percent at entrance to 14 percent at the time of the fifth donation. In summary, healthy elderly persons may contribute to the national blood resource; however, donations should probably be limited to less than five per year or donors should regularly take an iron supplement to preserve reasonable amounts of iron reserves.     

39Gastrointestinal electrical stimulation in post-surgical gastroparesis improves symptoms independently while gastric emptying response is dependent on baseline emptying

Introduction:  Temporary GES (tempGES) can improve both gastric emptying and symptoms in post-surgical gastroparesis (PS-GP). (SSAT 2004). Long-term effects on GI symptoms and gastric emptying are unknown. Since many PS-GP patients have non-delayed emptying, the long-term effect on baseline normal or rapid emptying is also unknown.
Patients:  36 pts (6 M, 30 F, mean age 42 years) with post-surgical: Bilroth I ( n  = 11), Bilroth II ( n  = 4), other gastric surgery ( n  = 21) disordered gastric emptying were evaluated.
Methods:  GI symptoms (vomiting = V, Total = TSS), and solid meal gastric emptying (GET) at 1 and 4 h, were compared at baseline (Base), after temporary (tempGES) and permanent (permGES) gastric electrical stimulation as previously described (NGM, 2004; 16: 635.) Long-term follow-up for permanent GES ranged from 6 month to 10 years. Results were compared by t-tests, and are reported as means ± SEM.
Results:  29 of the 36 patients were able to tolerate food for baseline quantitative gastric emptying testing. 20 patients had delayed and 9 patients had non-delayed gastric emptying, with 7/9 being rapid. With both tempGES and permGES, GI symptoms improved (p < 0.05). Both tempGES and permGES showed accelerated GET for delayed patients and generally slowed GET for non-delayed (p < 0.05 for 1 h values). See tables below.
Conclusions:  In a large group of post-surgical GP patients, temporary and permanent gastrointestinal electrical stimulation improved GI symptoms independent of gastric emptying and for a prolonged time. GES improves symptoms independent of baseline gastric emptying, and improves GET dependent on the baseline gastric emptying.
 

     

Hip fracture incidence among elderly Hispanics.

OBJECTIVES: This study estimated hip fracture incidence for elderly Hispanics in the United States. METHODS: A cohort of Spanish-surnamed 1992 Medicare enrollees was followed for 2 years. Hip fractures were identified by inpatient diagnostic code. RESULTS: For Hispanic women, the national age-adjusted hip fracture rate was 7.3 per 1000 person-years; for men, the rate was 3.3. Rates varied markedly, with higher rates for the predominantly Mexican-American southwestern states than for Puerto Ricans. CONCLUSIONS: Nationally, the Hispanic population is at intermediate risk of hip fracture between Blacks and Whites, but geographic variation suggests that Mexican Americans are at higher risk than Puerto Ricans.