Shock Following Subcutaneous Injections of Polymethylmethacrylate

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A dog model for acetaminophen-induced fulminant hepatic failure.

The development of a large animal model of fulminant hepatic failure produced with acetaminophen that should be useful in the development and evaluation of potential medical therapies for the important clinical problem of fulminant hepatic failure is described. Acetaminophen in dimethyl sulfoxide (600 mg/ml) given as three subcutaneous injections, with the first dose (750 mg/kg body wt) being given at noon, the second dose (200 mg/kg body wt) being given 9 h later, and the third dose (200 mg/kg body wt) being given 24 h after the initial dose consistently produces fulminant hepatic failure in dogs. The dimethyl sulfoxide vehicle, injected intramuscularly, does not influence either animal survival or hepatic function in control-treated dogs. No deaths occur within the first 36 h. By 72 h after initial drug administration, the mortality is 90%. Histopathological and biochemical investigations demonstrate a high degree of hepatocellular necrosis in nonsurviving animals without appreciable damage to the kidneys, lungs, or heart. The drug schedule and preparation outlined avoids the administration of large volumes of vehicle and results in prolonged high levels of acetaminophen in the blood sufficient to induce severe hepatic injury. Ranitidine (120 mg/kg body wt i.m.) given 30 min before each acetaminophen dose significantly reduces the mortality and hepatic necrosis produced using this model. This model satisfies all criteria established by Miller et al. for the production of a suitable large animal model of fulminant acute hepatic failure

A dog model for acetaminophen-induced fulminant hepatic failure.

The development of a large animal model of fulminant hepatic failure produced with acetaminophen that should be useful in the development and evaluation of potential medical therapies for the important clinical problem of fulminant hepatic failure is described. Acetaminophen in dimethyl sulfoxide (600 mg/ml) given as three subcutaneous injections, with the first dose (750 mg/kg body wt) being given at noon, the second dose (200 mg/kg body wt) being given 9 h later, and the third dose (200 mg/kg body wt) being given 24 h after the initial dose consistently produces fulminant hepatic failure in dogs. The dimethyl sulfoxide vehicle, injected intramuscularly, does not influence either animal survival or hepatic function in control-treated dogs. No deaths occur within the first 36 h. By 72 h after initial drug administration, the mortality is 90%. Histopathological and biochemical investigations demonstrate a high degree of hepatocellular necrosis in nonsurviving animals without appreciable damage to the kidneys, lungs, or heart. The drug schedule and preparation outlined avoids the administration of large volumes of vehicle and results in prolonged high levels of acetaminophen in the blood sufficient to induce severe hepatic injury. Ranitidine (120 mg/kg body wt i.m.) given 30 min before each acetaminophen dose significantly reduces the mortality and hepatic necrosis produced using this model. This model satisfies all criteria established by Miller et al. for the production of a suitable large animal model of fulminant acute hepatic failure

Necrotising fasciitis : a case report

Abstract Necrotising fasciitis is a rapidly progressive and potentially lifethreatening bacterial infection involving the subcutaneous tissues and fascia which can result in extensive tissue necrosis and severe sepsis. Key factors affecting survival include an early diagnosis, surgical debridement and the appropriate use of antimicrobials. We present a case in a diabetic patient with necrotizing fasciitis of the abdominal wall secondary to a subcutaneous saline infusion, describing the presentation, diagnosis and the successful treatment of this patient.peer-reviewe

Metabolic responses of lactating dairy cows to exogenous glucagon

Fatty liver is a major metabolic disorder of dairy cows in early lactation that compromises their health status and reproductive performance and in clinical cases decreases milk production and feed intake. Fatty liver can be treated with 14-d continuous, intravenous infusions of 10 mg/d of glucagon. The objective of the current study was to test whether treatment of fatty liver with 14-d subcutaneous injections of glucagon at 7.5 or 15 mg/d, which is more practical than infusion, would cause similar metabolic responses and improve health status and reproductive performance of dairy cows in early lactation. In the main study, multiparous Holstein cows (n = 32) were grouped on the basis of their liver triacylglycerol concentration at d 8 postpartum into Normal (n = 8; triacylglycerol \u3c 1% liver wet wt) and Susceptible (n = 24; triacylglycerol \u3e 1% liver wet wt) cows. Susceptible cows were assigned randomly to three groups and beginning at d 8 postpartum received 0 (same for Normal cows), 2.5, or 5 mg of glucagon in 60 ml 0.15 M NaCl by subcutaneous injections every 8 h for 14 d. Subcutaneous injections of 15 mg/d of glucagon consistently increased concentrations of plasma glucose and insulin for 4 h, decreased concentrations of liver triacylglycerol in cows older than 3.5 years, and tended to decrease concentrations of plasma NEFA and BHBA. The effects of 15 mg/d of glucagon were not limited to the treatment period, because glucagon decreased the incidence of mastitis and days to first ovarian activity after the injection period. These results document that subcutaneous injections of 15 mg/d of glucagon improve metabolic status throughout the injection period and have the potential to treat fatty liver in older cows. The improved metabolic status in cows treated with 15 mg/d of glucagon in early lactation has long-term beneficial effects by improving health status and reproductive performance during the entire lactation

To develop behavioral tests of vestibular functioning in the Wistar rat

Two tests of vestibular functioning in the rat were developed. The first test was the water maze. In the water maze the rat does not have the normal proprioceptive feedback from its limbs to help it maintain its orientation, and must rely primarily on the sensory input from its visual and vestibular systems. By altering lighting conditions and visual cues the vestibular functioning without visual cues was assessed. Whether there was visual compensation for some vestibular dysfunction was determined. The second test measured vestibular functioning of the rat's behavior on a parallel swing. In this test the rat's postural adjustments while swinging on the swing with the otoliths being stimulated were assessed. Less success was achieved in developing the parallel swing as a test of vestibular functioning than with the water maze. The major problem was incorrect initial assumptions of what the rat's probable behavior on the parallel swing would be

Suppression of antibody formation by the reticuloendothelial (RES)-blockade. I. Effects of the RES-blockade with macromolecular polyvinyl pyrrolidone

For the purpose of revealing the role of the reticuloendothelial system (RES) for the antibody formation, the rats which received the repeated intraperitoneal and subcutaneous injections of a vast amount of PVP were challenged by bovine serum albumin (BSA) introducing through 2 routes of intramuscular and intravenous, and then antibody formation was observed. Blood cell count and clearance rate of radiogold were observed for the purpose of obtaining the information of blockade grade of the RES by PVP. Phagocytic activity of macrophages ingesting PVP against iron colloid were also observed in vitro. 1. A severe anemia was induced by the administration of a vast amount of PVP, 15 ml of 3% solution daily or every other day for 63 days. Histological picture indicated the suppressed erythropoiesis probably by iron deficiency or the lowered iron transporting activity of the RES, as the anemia recovered after intraperitoneal iron injections. 2. With the generalized and marked swelling of the RES, the cells in germinal center of spleen and lymph nodes were extremely swollen and lymphocytes disappeared completely, suggesting that the macrophages in germinal center play an important role in reproduction and differentiation of lymphocytes. 3. The phagocytic activity of the RES as understood from the clearance rate of radiogold was suppressed only slightly even by a heavy deposition of PVP after the repeated injections. The state of blockade or the suppressed phagocytic activity persisted for 48 hours or more after the several PVP injections. However, complete blockade of the RES or inactivation of the phagocytic activity by PVP injection was not attained. 4. A prolonged treatment of animals with PVP caused delay in the appearance of circulating antibody but the final titration reached the same level as that of control. The data suggest that the blockade of the RES by PVP induces the delay in the transmittance of the information for the antibody formation from the macrophages to the immunologically competent cells but no delay in the ingesting antigen by the macrophages.</p

Metabolically Inactive Insulin Analog Prevents Type I Diabetes in Prediabetic NOD Mice

The purpose of this study was to determine the relative importance of the metabolic effects of insulin for diabetes prevention by administering insulin or an inactive insulin analog by daily subcutaneous injections to prediabetic mice. A recombinant monomeric human insulin analog, which does not bind to the insulin receptor as a consequence of an alteration of a single amino acid at position 25 of the B chain, was shown to be equally effective at diabetes prevention as was intact insulin. In contrast to native insulin, the insulin analog did not cause hypoglycemia after subcutaneous injection. The insulin analog, however, protected young adult mice from diabetes, even when it was initiated after the onset of extensive lymphocytic infiltration of the islets. Thus, preventative therapy by daily subcutaneous injections of insulin does not require the hypoglycemic response, or binding to the insulin receptor to prevent the onset of type I diabetes

Injectable and Spatially Patterned Microporous Annealed Particle (MAP) Hydrogels for Tissue Repair Applications.

Spatially patterned hydrogels are becoming increasingly popular in the field of regenerative medicine and tissue repair because of their ability to guide cell infiltration and migration. However, postfabrication technologies are usually required to spatially pattern a hydrogel, making these hydrogels difficult to translate into the clinic. Here, an injectable spatially patterned hydrogel is reported using hyaluronic acid (HA)-based particle hydrogels. These particle hydrogels are sequentially loaded into a syringe to form a pattern and, once injected, they maintain the pattern. The applicability of this hydrogel in a wound healing skin model, a subcutaneous implant model, as well as a stroke brain model is examined and distinct patterning in all models tested is shown. This injectable and spatially patterned hydrogel can be used to create physical or biochemical gradients. Further, this design can better match the scaffold properties within the physical location of the tissue (e.g., wound border vs wound center). This allows for better design features within the material that promote repair and regeneration