Antineoplastic effects of partially HLA-matched irradiated blood mononuclear cells in patients with renal cell carcinoma.

PURPOSE: Vaccines, cytokines, and other biologic-based therapies are being developed as antineoplastic agents. Many of these agents are designed to induce an autologous immune response directed against the malignancy. In contrast, hematopoietic stem-cell transplantation is being developed as a form of allogeneic immunotherapy. This study tests the tolerance and antineoplastic activity of sequential infusions of partially HLA-matched allogeneic blood mononuclear cells (obtained from relatives) when administered outside of the context of a hematopoietic stem-cell transplantation. The cells are irradiated to prevent graft-versus-host disease. PATIENTS AND METHODS: Fifteen patients with relapsed or refractory malignancies for which no standard therapy was available were enrolled onto a clinical trial designed to assess the tolerability and antineoplastic effects of irradiated partially HLA-matched blood mononuclear cells obtained from relatives. RESULTS: There was disease regression in three patients with metastatic renal cell carcinoma during treatment. There was disease progression in six patients with metastatic renal cell carcinoma and two patients with metastatic melanoma during treatment. There was no change in disease state in several other patients. CONCLUSION: Irradiated allogeneic blood mononuclear cells administered outside the context of hematopoietic stem-cell transplantation may induce disease responses in patients with relapsed or refractory malignancies. Transfusion of irradiated allogeneic blood mononuclear cells should be developed further as a novel therapeutic antineoplastic approach.     

The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies

The objective of this study was to examine the effects of the intakeof dietary fat upon colorectal cancer risk in a combined analysis of datafrom 13 case-control studies previously conducted in populations withdiffering colorectal cancer rates and dietary practices. Original datarecords for 5,287 cases of colorectal cancer and 10,470 controls werecombined. Logistic regression analysis was used to estimate odds ratios (OR)for intakes of total energy, total fat and its components, and cholesterol.Positive associations with energy intake were observed for 11 of the 13studies. However, there was little, if any, evidence of anyenergy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01,1.02, and 0.92 for quintiles of residuals of total fat intake (P trend =0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (Ptrend = 0.39). The analysis suggests that, among these case-control studies,there is no energy-independent association between dietary fat intake andrisk of colorectal cancer. It also suggests that simple substitution of fatby other sources of calories is unlikely to reduce meaningfully the risk ofcolorectal cancer.     

Contrast sensitivity through hybrid diffractive, Fresnel, and refractive prisms.

BACKGROUND: Fresnel and wedge-shaped refractive prisms are used diagnostically and therapeutically in clinical practice. This article extends the study on the effect of prisms on visual acuity to the effect on contrast sensitivity by membrane Fresnel (F), refractive (R), and newly designed hybrid diffractive (C) prisms (ComPrisms), which combine a wedge-shaped refractive prism with a diffractive element. METHODS: Vistech contrast sensitivity function (CSF) Charts A, B, and C were used to measure the monocular and binocular contrast sensitivity of 21 and 20 subjects, respectively. CSF was measured without prisms (U), through the hybrid diffractive prisms, membrane Fresnel prisms, and acrylic refractive prisms in powers of 20delta, 30delta, and 40delta. RESULTS: Repeated measures analysis of variance calculations resulted in significant main effects in contrast sensitivity across prism types, prism powers, and between monocular and binocular measurements. Results of the Scheffé test for all possible contrast sensitivity comparisons between spatial frequencies are provided. It was found that as prism power increased from 20delta to 40delta, the rate of reduction in area under the CSF curve of ComPrisms became half that of the refractive and Fresnel prisms. CONCLUSIONS: Although all three prism types reduced contrast sensitivity with respect to the unaided condition, the ComPrisms at all powers provided significantly better contrast sensitivity than the refractive or Fresnel prisms of equivalent power. Significant binocular summations in contrast sensitivity were found without prisms and across all prism types and powers.     

Hypnotic medication in the treatment of chronic insomnia: non nocere! Doesn't anyone care?

Chronic primary insomnia is a recurrent condition that negatively effects the daily functioning of patients, diminishing the quality of their lives. It is associated with, and in some situations, is a risk factor in both psychiatric (depression) and physical (cardiovascular) illness. Treatment effectiveness has been shown in the short term for both drug (benzodiazepine and benzodiazepine agonists) and behavioral treatment. Expert opinion has strongly advised against long-term drug treatment because of concerns about residual sedative effects, memory impairment, falls, respiratory depression, rebound insomnia, medication abuse, dose escalation, dependency and withdrawal difficulties, and an increased risk of death possibly associated with the current hypnotic medications. Many of these concerns could be made against using these agents at all. Worries about these potential problems are challenged by the widespread clinical practice of using hypnotic drugs long-term without any of these difficulties developing and with patients who feel their sleep and daily function function is improved with the nightly use of their sleeping pill. The ability to mount a randomized, placebo-controlled, parallel group, double-blind trial of hypnotic medication in primary insomnia may not be possible. We may have to develop large systematic clinical databases, a number of case series in effect, to monitor both emergent symptoms and possible clinical effectiveness. There is the additional concern that there is a reluctance to examine the long-term drug treatment of insomnia. This reluctance may reflect a negative moral judgement about treating primary insomnia with drugs, a sort of , rather than just a data based judiciousness.     

Neonatal and 5-year outcomes after birth at 30-34 weeks of gestation

OBJECTIVE: To evaluate the rates of in-hospital death, neonatal complications, and 5-year outcomes of infants born at 30-34 weeks of gestation. METHODS: In nine regions of France, all 2,020 stillbirths and live births at 30, 31, and 32 weeks in 1997 and all 457 births at 33 and 34 weeks in April and October 1997 were recorded. Survivors were evaluated at 5 years of age. RESULTS: Increasing gestational age from 30 to 34 weeks was associated with progressive decreases in in-hospital mortality (from 8.1% to 0.4%) and neonatal complications (respiratory distress syndrome, 43.8% to 2.6%; maternofetal infections, 7.2% to 2.6%; and severe white matter injury, 5.5% to 1.3%). Although infants at 33 and 34 weeks of gestation rarely experienced necrotizing enterocolitis, bronchopulmonary dysplasia, or nosocomial infections, they still required endotracheal ventilation, antibiotics, or parenteral nutrition. At 5 years of age, older gestational age was associated with significant decreases in rates of cerebral palsy (6.3% at 30 weeks and 0.7% at 34 weeks) and mild to severe cognitive impairments (35.3% at 30 weeks and 23.9% at 34 weeks). In singletons, preterm rupture of membranes or preterm labor carried an increased risk of cerebral palsy but not of cognitive impairment. CONCLUSION: Neonates born at 30-34 weeks experienced substantial morbidity and often required admission to neonatal intensive care units. These outcomes suggest that prolonging pregnancies beyond 34 weeks may be desirable whenever possible. Infants born at 30-34 weeks should be carefully monitored to ensure prompt detection and management of neurodevelopmental impairment.     

Calculating small-angle scattering intensity functions from electron-microscopy images

We outline procedures to calculate small-angle scattering (SAS) intensity functions from 2-dimensional electron-microscopy (EM) images. Two types of scattering systems were considered: (a) the sample is a set of particles confined to a plane; or (b) the sample is modelled as parallel, infinitely long cylinders that extend into the image plane. In each case, an EM image is segmented into particle instances and the background, whereby coordinates and morphological parameters are computed and used to calculate the constituents of the SAS-intensity function. We compare our results with experimental SAS data, discuss limitations, both general and case specific, and outline some applications of this method which could potentially complement experimental SAS.

We outline procedures to calculate small-angle scattering (SAS) intensity functions from 2-dimensional electron-microscopy (EM) images for two types of scattering systems.

The structures of nanoparticulate systems are commonly characterized by various forms of electron microscopy (EM) and small-angle scattering (SAS) methods. The size and shape of nanoparticles, as well as their spatial-distribution functions, are of particular interest since they govern their structure–function relationships and thus their nanotechnological prospects.^1–6 EM and SAS data are highly complementary. For example, the former images a specific section of a nanomaterial, while the latter realizes its bulk structure by averaging signals obtained from a larger overall area and depth reflective of the sample thickness and beam size. There exists a high degree of overlap in the length scale that is interrogated by EM and SAS data on the same nanomaterial. Yet, these data are necessarily acquired separately and they are analyzed independently. Nevertheless, if suitably processed, the data from one metrology could be used to reconstruct the other. This could draw out the maximum possible structural information about a nanomaterial, or allow data from both sources to be fused to obtain more accurate insights or even highlight processes that result in discrepancies between data from the two methods.This work presents two case studies in which we calculate SAS data from 2-D EM images where (1) the particles being characterized exist on a plane; (2) the sample being imaged can be modelled as parallel, infinitely long cylinders that extend into the image plane. In both cases, we discuss limitations that result in discrepancies between image-obtained SAS intensities and those obtained experimentally. Despite these limitations, we discuss how this method can be complementary to small-angle scattering measurements, by informing experimental design decisions and aiding in model selection. The second case that we present was partially explored by Worthington and Inouye,⁷ and later Meek and Quantock⁸ as well as Quantock et al.⁹ They studied the interfibril distance of collagen fibres in animal corneas by calculating an interference function from pairwise distances of points obtained from an EM image. Their interference function is related to the structure factor which we include in our calculation of SAS intensities, along with form factors which we additionally compute from images. Grubb et al.¹⁰ studied the effect of the orientation of lamellar stack structures on SAXS patterns. The authors did this by generating synthetic images of arrays of lamellar stacks and simulating SAXS data using the 2-D Fourier transform, where they use the Fourier Slice theorem to obtain a 2-D slice of the 3-D transform.¹¹ Afsari et al.¹² and Kim et al.¹³ outline a procedure for calculating small-angle X-ray scattering (SAXS) data from cryo-EM images. Their work makes use of the fact that averaging the correlation functions of many cryo-EM images is equivalent to the Abel transform of SAXS data. Their work is complementary to ours as both methods can be applied under different circumstances. Our work is relevant in situations where image-processing and computer-vision techniques can be employed to segment single EM images and determine morphological and structural information about the scatterers; theirs is relevant when one has numerous cryo-EM images of the same sample.