Topical administration of a granular mineral hemostatic agent to a variety of wounds in an experimental swine model resulted in thermal tissue injury and necrosis. Suggestions for reducing the extent of injury with this product are offered.
Trichloroethylene (TCE), trichloroacetic acid (TCA), and dichloroacetic acid (DCA) are commonly found as groundwater contaminants in many regions of the United States. Cardiac birth defects in children have been associated with TCE, and laboratory studies with rodents report an increased incidence of fetal cardiac malformations resulting from maternal exposures to TCE, TCA, and DCA. The objective of this study was to orally treat pregnant CDR(CD) Sprague-Dawley rats with large bolus doses of either TCE (500 mg/kg), TCA (300 mg/kg), or DCA (300 mg/kg) once per day on days 6 through 15 of gestation to determine the effectiveness of these materials to induce cardiac defects in the fetus. All-trans retinoic acid (RA) dissolved in soybean oil was used as a positive control. Soybean oil is commonly used as a dosing vehicle for RA teratology studies and was also used in this study as a dosing vehicle for TCE. Water was used as the dosing vehicle for TCA and DCA. Fetal hearts were examined on gestation day (GD) 21 by an initial in situ, cardiovascular stereomicroscope examination, and then followed by a microscopic dissection and examination of the formalin-fixed heart. The doses selected for TCA and DCA resulted in a modest decrease in maternal weight gain during gestation (3% to 8%). The fetal weights on GD 21 in the TCA and DCA treatment groups were decreased 8% and 9%, respectively, compared to the water control group and 21% in the RA treatment group compared to soybean oil control group. The heart malformation incidence for fetuses from the TCE-, TCA-, and DCA-treated dams did not differ from control values on a per fetus or per litter basis. The rate of heart malformations, on a per fetus basis, ranged from 3% to 5% for TCE, TCA, and DCA treatment groups compared to 6.5% and 2.9% for soybean oil and water control groups. The RA treatment group was significantly higher with 33% of the fetuses displaying heart defects. For TCE, TCA, and DCA treatment groups 42% to 60% of the litters contained at least one fetus with a heart malformation, compared to 52% and 37% of the litters in the soybean oil and water control groups. For the RA treatment group, 11 of 12 litters contained at least one fetus with a heart malformation. Further research is needed to quantify the spontaneous rates of heart defects for vehicle control rats and to explain the disparity between findings in the present study and other reported findings on the fetal cardiac teratogenicity of TCE, TCA, and DCA.
The purpose of our randomized, double-blind, placebo-controlled crossover study in 15 patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) because of single large-scale mitochondrial (mt) DNA deletions was to determine whether oral creatine (Cr) monohydrate can improve skeletal muscle energy metabolism in vivo. Each treatment phase with Cr in a dosage of 150 mg/kg body weight/day or placebo lasted 6 weeks. The effect of Cr was estimated by phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS), clinical and laboratory tests. (31)P-MRS analysis prior to treatment showed clear evidence of severe mitochondrial dysfunction. However, there were no relevant changes in (31)P-MRS parameters under Cr. In particular, phosphocreatine (PCr)/ATP at rest did not increase, and there was no facilitation of post-exercise PCr recovery. Clinical scores and laboratory tests did not alter significantly under Cr, which was tolerated without major side-effects in all patients. Cr supplementation did not improve skeletal muscle oxidative phosphorylation in our series of patients. However, one explanation for our negative findings may be the short study duration or the limited number of patients included.
Low-volume resuscitation with HBOC-201 provides adequate tissue oxygenation for survival in a porcine model of controlled hemorrhagic shock with no long-term organ dysfunction identified. Although some animals did show mild hepatocellular damage with elevations of aspartate aminotransferase at day 2, these findings did not appear to have clinical relevance, and the enzyme elevations were trending toward normal by the third postoperative day. Decreases in hemoglobin levels at the later time points were expected, given the half-life of the product.
To better understand the cellular and molecular responses to overexposure to millimeter waves, alterations in the gene expression profile and histology of skin after exposure to 35 GHz radiofrequency radiation were investigated. Rats were subjected to sham exposure, to 42 degrees C environmental heat, or to 35 GHz millimeter waves at 75 mW/cm(2). Skin samples were collected at 6 and 24 h after exposure for Affymetrix GeneChip analysis. The skin was harvested from a separate group of rats at 3-6 h or 24-48 h after exposure for histopathology analysis. Microscopic findings observed in the dermis of rats exposed to 35 GHz millimeter waves included aggregation of neutrophils in vessels, degeneration of stromal cells, and breakdown of collagen. Changes were detected in 56 genes at 6 h and 58 genes at 24 h in the millimeter-wave-exposed rats. Genes associated with regulation of transcription, protein folding, oxidative stress, immune response, and tissue matrix turnover were affected at both times. At 24 h, more genes related to extracellular matrix structure and chemokine activity were altered. Up-regulation of Hspa1a, Timp1, S100a9, Ccl2 and Angptl4 at 24 h by 35 GHz millimeter-wave exposure was confirmed by real-time RT-PCR. These results obtained from histopathology, microarrays and RT-PCR indicate that prolonged exposure to 35 GHz millimeter waves causes thermally related stress and injury in skin while triggering repair processes involving inflammation and tissue matrix recovery.
An 8-year-old male Belgian Malinois was referred for evaluation of progressive caudal paresis of 2 to 3 weeks' duration. Radiography revealed a mottled appearance to the body of L4 and misshapen intervertebral foramen at L4-L5. Myelography revealed that the dye column terminated within the body of L4. Computed tomography revealed a soft tissue mass adjacent to or involving the spinal cord and L4, with complete destruction of a portion of the floor of the vertebral foramen. Small circular lesions were also noticed within the body of L3 and L5. A left-sided hemilaminectomy was performed. Histologic examination of a biopsy specimen revealed a high-grade sarcoma. Because of the poor prognosis, the dog was euthanatized. Necropsy examination revealed osteosarcoma, with lesions in L3 to L7, the sacrum, and the lungs. Metastatic lesions in adjacent bones have been termed skip metastases and the primary tumor is typically in long bones. Prognosis associated with skip metastases is similar to or even graver than that associated with pulmonary metastases. In the dog of the present report, the unusual finding of distinct foci of osteosarcoma within 5 adjacent lumbar vertebrae and the sacrum was consistent with skip metastases, potentially spread via the vertebral venous plexus.
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