Reducing X-ray imaging for proton postmastectomy chest wall patients

Purpose

Proton postmastectomy radiation therapy (PMRT) patients are positioned daily using surface imaging with additional x-ray imaging for confirmation. This study aims to investigate whether weekly x-ray imaging with daily surface imaging, as performed for photon treatment, is sufficient to maintain PMRT patient positioning fidelity.

Total Parenteral Nutrition in the Critically Ill Patient: A Meta-analysis

Context.— Nutritional support has become a standard of care for hospitalized patients, but whether total parenteral nutrition (TPN) affects morbidity and mortality is unclear. Objective.— To examine the relationship between TPN and complication and mortality rates in critically ill patients. Data Sources.— Computerized search of published research on MEDLINE from 1980 to 1998, personal files, and review of relevant reference lists. Study Selection.— We reviewed 210 titles, abstracts, and papers. Primary studies were included if they were randomized clinical trials of critically ill or surgical patients that evaluated the effect of TPN (compared with standard care) on complication and mortality rates. We excluded studies comparing TPN with enteral nutrition. Data Extraction.— Relevant data were abstracted on the methodology and outcomes of primary studies. Data were abstracted in duplicate, independently. Data Synthesis.— There were 26 randomized trials of 2211 patients comparing the use of TPN with standard care (usual oral diet plus intravenous dextrose) in surgical and critically ill patients. When the results of these trials were aggregated, TPN had no effect on mortality (risk ratio [RR], 1.03; 95% confidence interval [CI], 0.81-1.31). Patients who received TPN tended to have a lower complication rate, but this result was not statistically significant (RR, 0.84; 95% CI, 0.64-1.09). We examined several a priori hypotheses and found that studies including only malnourished patients were associated with lower complication rates but no difference in mortality when compared with studies of nonmalnourished patients. Studies published since 1989 and studies with a higher methods score showed no treatment effect, while studies published in 1988 or before and studies with a lower methods score demonstrated a significant treatment effect. Complication rates were lower in studies that did not use lipids; however, there was no difference in mortality rates between studies that did not use lipids and those studies that did. Studies limited to critically ill patients demonstrated a significant increase in complication and mortality rates compared with studies of surgical patients. Conclusions.— Total parenteral nutrition does not influence the overall mortality rate of surgical or critically ill patients. It may reduce the complication rate, especially in malnourished patients, but study results are influenced by patient population, use of lipids, methodological quality, and year of publication.      

Changes in intracellular free Ca ion concentration evoked by electrical activity in cat spinal neurons in situ

In cats under allobarbitone anaesthesia, Ca2+-sensitive microelectrodes were inserted into the lumbosacral spinal neurons to measure intracellular free Ca2+ concentration [Ca]i. In 72 resting motoneurons, the global mean [Ca]i was 7.9 microM (SD +/- 25.9). In the 36 "best" cells (with resting and action potentials better than 60 mV), mean [Ca]i was 1.6 microM (SD +/- 1.64). Activation of motoneurons by antidromic or direct stimulation evoked mean increases in [Ca]i of about 90 nM when stimulating for 30 s at 10 Hz, and 170 nM at 20 Hz. The mean time to half-recovery was 23 s (SD +/- 14.5). Orthodromic stimulation consistently produced smaller increases in [Ca]i. Measurements in motor axons showed a comparable resting level of [Ca]i, but only minimal changes during stimulation, even at 100 Hz. Sensory axons (also recorded within the spinal cord) similarly failed to show any increase in [Ca]i during high frequency stimulation. In some interneurons, however, particularly large and rapid increases in [Ca]i could be evoked by dorsal root stimulation at 1-5 Hz. Unresponsive cells (presumably neuroglia), with a typically high and stable resting potential, had a variable [Ca]i giving a mean of 32 microM (SD +/- 63.0). A tentative theoretical analysis of the magnitude and time course of delta [Ca]i evoked in motoneurons by tetanic stimulation is consistent with remarkably slow apparent diffusion of intracellular Ca2+ (1/250 of rate of diffusion in water), such as might be expected in the presence of very efficient mechanisms of Ca2+ sequestration.     

Antigen-presenting cells recruited by Brugia malayi induce Th2 differentiation of naïve CD4(+) T cells

A key feature of nematode infection is a bias towards a type 2 immune response. To investigate the role that antigen-presenting cells (APC) may play in promoting this bias, we used adherent peritoneal exudate cells (PEC) recruited in response to the filarial nematode Brugia malayi, to stimulate na?ve T cells from pigeon cytochrome c (PCC)-specific TCR transgenic (PCC-tg) mice. Although the proliferation of PCC-tg T cells was inhibited by parasite- induced PEC during primary stimulation, they proliferated normally upon secondary stimulation and were not rendered anergic. However, PCC-tg T cells primed by suppressive APC differentiated into IL-4-producing Th2 cells upon secondary stimulation instead of IFN-gamma-producing Th1 cells, as has been previously described. Studies with carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled cells indicated that Th2 differentiation was associated with the inhibition of (or failure to stimulate) IFN-gamma production during primary stimulation. Interestingly, blocking antibodies against TGF-beta (but not IL-10) restored the differentiation of IFN-gamma-producing Th1 cells. Identical results with CFSE-labeled cells were obtained using purified IL-4-dependent F4/80(+) macrophages. These data indicate that T cells exposed to parasite-induced alternatively activated macrophages are driven towards Th2 differentiation. This may be an important factor in the Th2 bias that accompanies nematode infection.     

T cell receptor α gene rearrangement and transcription in adult thymic γδ cells

T cells belong to two separate lineages based on surface expression of αβ or γδ T cell receptors (TCR). Since during thymus development TCR β, γ, and δ genes rearrange before α genes, and γδ cells appear earlier than αβ cells, it has been assumed that αδ cells are devoid of TCR α rearrangements. We show here that this is not the case, since mature adult, but not fetal, thymic γδ cells undergo VJα rearrangements more frequently than immature αβ lineage thymic precursors. Sequence analysis shows VJα rearrangements in γδ cells to be mostly (70 %) nonproductive. Furthermore, VJα rearrangements in γδ cells are transcribed normally and, as shown by analysis of TCR β-/- mice, occur independently of productive VDJβ rearrangements. These data are interpreted in the context of a model in which precursors of αβ and γδ cells differ in their ability to express a functional pre-TCR complex.     

Inflammation reduces the contribution of N-type calcium channels to primary afferent synaptic transmission onto NK1 receptor-positive lamina I neurons in the rat dorsal horn

N-type calcium channels contribute to the release of glutamate from primary afferent terminals synapsing onto nocisponsive neurons in the dorsal horn of the spinal cord, but little is known of functional adaptations to these channels in persistent pain states. Subtype-selective conotoxins and other drugs were used to determine the role of different calcium channel types in a rat model of inflammatory pain. Electrically evoked primary afferent synapses onto lumber dorsal horn neurons were examined three days after induction of inflammation with intraplantar complete Freund's adjuvant. The maximal inhibitory effect of the N-type calcium channel blockers, ω-conotoxins CVID and MVIIA, were attenuated in NK1 receptor-positive lamina I neurons after inflammation, but the potency of CVID was unchanged. This was associated with reduced inhibition of the frequency of asynchronous-evoked synaptic events by CVID studied in the presence of extracellular strontium, suggesting reduced N-type channel contribution to primary afferent synapses after inflammation. After application of CVID, the relative contributions of P/Q and L channels to primary afferent transmission and the residual current were unchanged by inflammation, suggesting the adaptation was specific to N-type channels. Blocking T-type channels did not affect synaptic amplitude under control or inflamed conditions. Reduction of N-type channel contribution to primary afferent transmission was selective for NK1 receptor-positive neurons identified by post hoc immunohistochemistry and did not occur at synapses in laminae II_o or II_i, or inhibitory synapses. These results suggest that inflammation selectively downregulates N-type channels in the terminals of primary afferents synapsing onto (presumed) nociceptive lamina I NK1 receptor-positive neurons.     

Intracellular pathway of interleukin 2 following receptor-mediated endocytosis

Electron microscope autoradiography was used to examine the intracellular pathway of radioiodinated interleukin 2 [( 125I]IL2) following its receptor-mediated endocytosis in CTLL cells. Direct measurement of the kinetics of endocytosis showed that 60-70% of surface-bound [125I]IL2 was internalized after 1 h at 37 degrees C. [125I]IL2 was observed to enter cells through invagination of coated pits at the cell surface and to concentrate into lysosomal multivesicular bodies as early as 5-10 min after endocytosis. These results provide ultrastructural information on the intracellular pathway of IL2 and on its probable site of degradation within the cell.     

A diagnostic approach to syndromic retinal dystrophies with intellectual disability

Inherited retinal dystrophies are a group of monogenic disorders that, as a whole, contribute significantly to the burden of ocular disease in both pediatric and adult patients. In their syndromic forms, retinal dystrophies can be observed in association with intellectual disability, frequently alongside other systemic manifestations. There are now over 80 genes implicated in syndromic retinal dystrophies with intellectual disability. Identifying and accurately characterizing these disorders allows the clinician to narrow the differential diagnosis, evaluate for relevant associated features, arrive at a timely and accurate diagnosis, and address both sight‐threatening ocular manifestations and morbidity‐causing systemic manifestations. The co‐occurrence of retinal dystrophy and intellectual disability in an individual can be challenging to investigate, diagnose, and counsel given the considerable phenotypic and genotypic heterogeneity that exists within this broad group of disorders. We performed a review of the current literature and propose an algorithm to facilitate the evaluation, and clinical and mechanistic classification, of these individuals.