Histology of esophageal mucosa from patients with achalasia

When achalasia becomes far advanced and leads to esophageal resection, inflammation of the esophageal mucosa is almost universal. The histology of the esophageal mucosa in less advanced cases of achalasia has not been firmly established. We have studied endoscopic biopsies obtained during evaluation of patients with achalasia. Two to four endoscopic biopsies from the lower esophagus of 26 patients with manometrically verified achalasia were mounted on mesh, serially sectioned, stained, coded and interpreted by two independent observers using recognized criteria. The histological findings were correlated with clinical data. Ten of 26 patients had at least one abnormal biopsy. Five of these 10 patients had a previous Heller myotomy; another patient had several pneumatic dilatations, and two other patients had endoscopically proven candida infections. Of the 16 patients with normal histology, four had prolonged stasis, five had heartburn and one patient had both heartburn and stasis. Unless the patient with achalasia has had a Heller myotomy, balloon dilatation, or a candida infection, the esophageal mucosa on biopsy appears to be within normal limits, even in patients with years of esophageal stasis or complaints of heartburn.     

Post‐Traumatic Headaches in Civilians and Military Personnel: A Comparative,Clinical Review

Post‐traumatic headache (PTH) is the most frequent symptom after traumatic brain injury (TBI). We review the epidemiology and characterization of PTH in military and civilian settings. PTH appears to be more likely to develop following mild TBI (concussion) compared with moderate or severe TBI. PTH often clinically resembles primary headache disorders, usually migraine. For migraine‐like PTH, individuals who had the most severe headache pain had the highest headache frequencies. Based on studies to date in both civilian and military settings, we recommend changes to the current definition of PTH. Anxiety disorders such as post‐traumatic stress disorder (PTSD) are frequently associated with TBI, especially in military populations and in combat settings. PTSD can complicate treatment of PTH as a comorbid condition of post‐concussion syndrome. PTH should not be treated as an isolated condition. Comorbid conditions such as PTSD and sleep disturbances also need to be treated. Double‐blind placebo‐controlled trials in PTH population are necessary to see whether similar phenotypes in the primary headache disorders and PTH will respond similarly to treatment. Until blinded treatment trials are completed, we suggest that, when possible, PTH be treated as one would treat the primary headache disorder(s) that the PTH most closely resembles.     

Separation of Spleen Colony Forming Units (CFU-S) from Mouse Bone Marrow Cells Using Velocity Sedimentation in an Isokinetic Gradient of Ficoll in Tissue Culture Medium

Spleen colony forming cells (CFU-S) from mouse bone marrow were concentrated using velocity sedimentation in an isokinetic gradient of Ficoll (polysucrose) in tissue culture medium. Following separation, CFU-S were found as a sharp modal population of cells which was discrete from the modal populations of lymphocytes and other cell types. Despite the wide separation of lymphocytes, granulocytes and CFU-S in the density gradient, there was no appreciable resolution of CFU-S specifically committed to erythroid, granulocytic or undifferentiated colony formation. This suggests that committed stem cells either share identical physical properties or are not detected by the spleen colony assay. In the purest fractions from the isokinetic gradient, CFU-S were 2.8- to 4.7-fold purified when compared with mouse bone marrow before separation.     

Differential vulnerability of white matter structures to experimental infantile hydrocephalus detected by diffusion tensor imaging

Purpose

The differential vulnerability of white matter (WM) to acute and chronic infantile hydrocephalus and the related effects of early and late reservoir treatment are unknown, but diffusion tensor imaging (DTI) could provide this information. Thus, we characterized WM integrity using DTI in a clinically relevant model.

Methods

Obstructive hydrocephalus was induced in 2-week-old felines by intracisternal kaolin injection. Ventricular reservoirs were placed 1 (early) or 2 (late) weeks post-kaolin and tapped frequently based solely on neurological deficit. Hydrocephalic and age-matched control animals were sacrificed 12 weeks postreservoir. WM integrity was evaluated in the optic system, corpus callosum, and internal capsule prereservoir and every 3 weeks using DTI. Analyses were grouped as acute (<6 weeks) or chronic (≥6 weeks).

Results

In the corpus callosum during acute stages, fractional anisotropy (FA) decreased significantly with early and late reservoir placement (p?=?0.0008 and 0.0008, respectively), and diffusivity increased significantly in early (axial, radial, and mean diffusivity, p?=?0.0026, 0.0012, and 0.0002, respectively) and late (radial and mean diffusivity, p?=?0.01 and 0.0038, respectively) groups. Chronically, the corpus callosum was thinned and not detectable by DTI. FA was significantly lower in the optic chiasm and tracts (p?=?0.0496 and 0.0052, respectively) with late but not early reservoir placement. In the internal capsule, FA in both reservoir groups increased significantly with age (p?Conclusions All hydrocephalic animals treated with intermittent ventricular reservoir tapping demonstrated progressive ventriculomegaly. Both reservoir groups demonstrated WM integrity loss, with the CC the most vulnerable and the optic system the most resilient.     

Pyruvate carboxylase is critical for non–small-cell lung cancer proliferation

Anabolic biosynthesis requires precursors supplied by the Krebs cycle, which in turn requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the activity of pyruvate carboxylase (PC) and glutaminase 1 (GLS1), respectively. Due to their rapid proliferation, cancer cells have increased anabolic and energy demands; however, different cancer cell types exhibit differential requirements for PC- and GLS-mediated pathways for anaplerosis and cell proliferation. Here, we infused patients with early-stage non–small-cell lung cancer (NSCLC) with uniformly ¹³C-labeled glucose before tissue resection and determined that the cancerous tissues in these patients had enhanced PC activity. Freshly resected paired lung tissue slices cultured in ¹³C₆-glucose or ¹³C₅,¹⁵N₂-glutamine tracers confirmed selective activation of PC over GLS in NSCLC. Compared with noncancerous tissues, PC expression was greatly enhanced in cancerous tissues, whereas GLS1 expression showed no trend. Moreover, immunohistochemical analysis of paired lung tissues showed PC overexpression in cancer cells rather than in stromal cells of tumor tissues. PC knockdown induced multinucleation, decreased cell proliferation and colony formation in human NSCLC cells, and reduced tumor growth in a mouse xenograft model. Growth inhibition was accompanied by perturbed Krebs cycle activity, inhibition of lipid and nucleotide biosynthesis, and altered glutathione homeostasis. These findings indicate that PC-mediated anaplerosis in early-stage NSCLC is required for tumor survival and proliferation.     

Spurious Ampicillin Resistance by Testing Haemophilus influenzae with Agar Containing Supplement C

Ampicillin resistance (minimal inhibitory concentration >/=10 mug/ml) in the absence of beta-lactamase activity by Haemophilus influenzae was noted in tests performed with Mueller-Hinton agar containing one lot of supplement C. All strains, except five with known resistance due to beta-lactamase activity, were inhibited by 0.6 mug or less of ampicillin per ml of chocolatized blood agar.