Dexamethasone impairs hypoxia-inducible factor-1 function.

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription-factor composed of alpha- and beta-subunits. HIF-1 is not only necessary for the cellular adaptation to hypoxia, but it is also involved in inflammatory processes and wound healing. Glucocorticoids (GC) are therapeutically used to suppress inflammatory responses. Herein, we investigated whether GC modulate HIF-1 function using GC receptor (GR) possessing (HepG2) and GR deficient (Hep3B) human hepatoma cell cultures as model systems. Dexamethasone (DEX) treatment increased HIF-1alpha levels in the cytosol of HepG2 cells, while nuclear HIF-1alpha levels and HIF-1 DNA-binding was reduced. In addition, DEX dose-dependently lowered the hypoxia-induced luciferase activity in a reporter gene system. DEX suppressed the hypoxic stimulation of the expression of the HIF-1 target gene VEGF (vascular endothelial growth factor) in HepG2 cultures. DEX did not reduce hypoxically induced luciferase activity in HRB5 cells, a Hep3B derivative lacking GR. Transient expression of the GR in HRB5 cells restored the susceptibility to DEX. Our study discloses the inhibitory action of GC on HIF-1 dependent gene expression, which may be important with respect to the impaired wound healing in DEX-treated patients.

Mediastinoscopy for extrathoracic malignancies.

Metastatic tumors from extrathoracic sources appear in the mediastinum infrequently and from a variety of locations. In this series of approximately 350 malignancies of the mediastinum, 20 (6%) originated from the breast, prostate, kidney, pelvis, and gastrointestinal tract. A radiologic review of these cases does not identify a unique pattern, although paratracheal masses present most often, while unilateral hilar adenopathy occurs somewhat less frequently. The history of previous surgery for malignancy suggests metastatic disease into the mediastinum. However, other entities of second primaries, lymphoma, Hodgkin's disease, and benign processes warrant consideration. Mediastinoscopy is reemphasized as a valuable diagnostic technique for the solution of these problems.

Effect of reconstituting field-dried and early-harvested sorghum grain on the ensiling characteristics of the grain and on growth performance and carcass merit of feedlot heifers.

The objective of this study was to determine whether reconstituting field-dried and early-harvested sorghum grain affected the fermentation characteristics and feed value of the ensiled grain when fed to feedlot heifers. In Trial 1, sorghum grain was harvested at 14% moisture, rolled, and reconstituted to 25, 30, or 35% moisture, then ensiled in laboratory-scale silos. Lactic acid concentration increased (d 5 to 90) and pH decreased more rapidly (d 3 to 90) as moisture level increased (P < .05). Acetic acid concentration increased (P < .05) with moisture and day postfilling. Concentration of ethanol was highest (P < .05) in the 30 and 35% moisture grains from d 1 to 5, but by d 90 the ethanol concentration in the 25% moisture grain exceeded (P < .05) that of the two higher-moisture grains. Ammonia N concentration was lowest (P < .05) in the 25% moisture grain at all sampling times postfilling. In Trial 2, 288 heifers (BW = 286+/-83 kg) were used to compare the feeding value of rolled, ensiled sorghum grain harvested at 25% moisture to the same grain reconstituted to 30 or 35% moisture. A steam-flaked corn (SFC) diet served as the control. Final live weight; ADG; hot carcass weight; backfat depth; marbling score; kidney, pelvic, and heart fat; and liver abscess score were not affected by grain treatment (P > .10). Dry matter intake was highest (P < .10) for heifers fed the 25 or 30% moisture sorghum grain diets and lowest for those fed the SFC diet; DMI for heifers fed the 35% moisture sorghum grain diet was intermediate. Feeding 35% moisture sorghum grain improved gain efficiency (P < .10) compared with feeding 25 or 30% moisture sorghum grain by 9.0 and 5.7%, respectively. We conclude that reconstituting sorghum grain beyond the typical moisture levels of 25 to 30% would enhance the fermentation characteristics of the ensiled grain and improve gain efficiency in feedlot heifers.

Effects of feeding combinations of steam-flaked grain sorghum and steam-flaked, high-moisture, or dry-rolled corn on growth performance and carcass characteristics in feedlot cattle.

The objective of these two feeding trials was to determine the associative effects of feeding steam-flaked grain sorghum (SFGS) in combination with steam-flaked (SFC), dry-rolled (DRC), or high-moisture (HMC) corn on growth performance and carcass characteristics in feedlot cattle. In Trial 1, 200 yearling heifers were blocked by weight, allotted to 25 pens, and fed one of five finishing diets (77% grain, 15% corn silage, and 8% supplement on a DM basis) for an average of 137 d. The grain combinations were 100:0, 75:25, 50:50, 25:75, and 0:100 SFC:SFGS, respectively. Treatment had no effect on DMI (P > .05), but ADG, gain efficiency, and final live and hot carcass weights decreased linearly (P < .05) as the proportion of SFGS increased in the diet. Carcass backfat, quality grade, and liver abscess score were not affected (P > .05) by treatment. In Trial 2, 306 yearling steers were blocked by weight, allotted to 30 pens, and fed diets that contained 74.5% grain, 10% corn silage, 7.5% soybean meal, 4% tallow, and 4% supplement (DM basis) for an average of 139 d. The grain and grain combinations were 100% DRC, HMC, SFC, or SFGS and a 67%:33% combination of SFGS: DRC or SFGS:HMC. For steers fed diets containing a single source of grain, those fed SFC gained 7% more live weight and had a 7% higher gain efficiency (P < .05) than those fed DRC or HMC. Growth performance of steers fed SFGS was intermediate. Feeding grain combinations (67% SFGS:33% HMC or DRC) resulted in a 5 to 6% positive associative effect (P < .05) for ADG and gain efficiency. Carcass characteristics were not affected (P > .05) by treatment. We concluded that there were significant benefits (positive associative effects) when SFGS was fed in combination with DRC or HMC, but the effects were smaller when SFGS was fed in combination with SFC.

Wheat middlings in high-concentrate diets: feedlot performance, carcass characteristics, nutrient digestibilities, passage rates, and ruminal metabolism in finishing steers.

We conducted two experiments to determine the feeding value and effects on diet digestibilities, passage rates, and ruminal metabolism of wheat middlings (WM) fed as a replacement for either the concentrate or roughage components of finishing diets of steers. In Exp. 1, 120 medium-framed steers were blocked by weight and randomly allocated to one of six treatments of high-concentrate diets: control (0%); 5, 10, or 15% pelleted WM replacing dry-rolled corn (DRC); and 5 or 10% pelleted WM replacing chopped alfalfa hay (ALF) components of the diet. Increasing WM replacement of DRC increased DMI (P < .01) and feed:gain ratio (FG; P < .05) linearly. A 9.2% increase in daily DMI and 10.1% increase in FG were observed at 15% of WM. Daily gain and final weight of the steers were not influenced by WM replacement of DRC. The WM replacement of ALF decreased (P < .01) daily DMI linearly, but it had no effect on ADG, final weight, or FG. In Exp. 2, six medium-framed steers, fitted with ruminal cannulas, were used in a 6 x 6 Latin square design with the same treatments as described in Exp. 1. Dry matter, OM, and starch digestibilities decreased (P < .01) by increasing replacement of DRC with WM, and replacing ALF increased DM and OM digestibilities linearly (P < .01). Wheat middlings could replace only up to 5% of DRC without reducing feed conversion efficiency and diet digestibilities, but complete (100%) or partial (50%) replacement of ALF increased digestibilities of DRC finishing diets.

Glomus jugulare tumor. Disseminated form in the central nervous system.

We will describe a case of glomus jugulare tumor that illustrates the potential for multiple areas of metastasis throughout the central nervous system. Extension through the dura into the subarachnoid space allows seeding via the cerebrospinal fluid as far away as the cauda equina. We will review the usual clinical course of the tumor and will evaluate the symptoms relative to the location of extension. In this case, the symptoms related to increased intracranial pressure with brain stem compression, which progressed rapidly to cause the patient's death.