Electrolyte disorders associated with respiratory distress syndrome and bronchopulmonary dysplasia.

In understanding the various electrolyte disorders associated with respiratory failure, one has to appreciate how the otherwise healthy premature infant maintains extracellular fluid homeostasis. The same physiologic processes that regulate body fluids are affected to varying degrees in the infant with respiratory failure. Maintenance of sodium conservation by the kidney is of critical importance for survival and growth. The immature kidney tends to exhibit excessive sodium wasting especially early on, but appropriate positive sodium balance is achieved generally within the first week. Appropriate reduction in extracellular fluid occurring during the first week or so of life is expected and if it is not allowed to occur may result in dilutional hyponatremia and an increase in pulmonary interstitial water. Diuretics, when used to promote an increase in lung compliance, can themselves generate significant morbidity. Sodium depletion, hypokalemia, alkalosis, and calcium wasting all can either be caused by or exaggerated by the loop diuretics. Thus, one must consider the maturational state of the infant, the infant's response to pulmonary failure, and iatrogenic factors influencing the outcome.     

Transgenic technology in farm animals--progress and perspectives

Current applications of gene transfer in farm animals include the improvement of product quality and quantity, disease resistance, the production of valuable proteins in the mammary gland or other organs, the genetic modification of pigs for xenotransplantation and the generation of new animal models in cases where rodent models are not sufficient for studying the problem under evaluation. Although DNA microinjection into pronuclei of zygotes from various farm animal species has happened since 1985, the efficiency of this method is low. Further drawbacks are related to the random integration process which may cause mosaicism, insertional mutations and varying expression due to position effects. Sperm-mediated gene transfer is not routinely established yet, although the mechanisms of binding and internalisation of DNA by sperm cells is becoming increasingly clearer. New protocols for the use of retroviral vectors to infect metaphase II oocytes which are subsequently fertilised resulted in efficient production of transgenic cattle. In spite of extensive efforts to establish pluripotent stem cells from farm animal species, no germ-line competent cells have been reported in mammalian species other than mouse so far. However, recent success in cloning sheep, cattle, goats and pigs from cultured cells provides an alternative route for efficient and targeted genetic modifications of farm animals.     

Polilactofate microspheres for Paclitaxel delivery to central nervous system malignancies.

PURPOSE: The purpose of this study was to demonstrate that surgically implanted, controlled-release, biodegradable polilactofate microspheres (Paclimer) can be used safely to bypass the blood-brain barrier and deliver paclitaxel to malignant brain tumors. EXPERIMENTAL DESIGN: The rate of paclitaxel release from Paclimer microspheres submerged in PBS was measured in vitro by high-performance liquid chromatography. In vivo studies of Paclimer were performed as intracranial implants in Fischer 344 rats in the presence or absence of 9L gliosarcoma. Mantel-Cox statistics were used to assess the efficacy of Paclimer at extending survival of tumor-bearing animals compared with control implants. Paclimer implants tagged with [(3)H]paclitaxel were used to measure biodistribution of paclitaxel from the Paclimer implant. RESULTS: Paclimer released paclitaxel at a constant rate for up to 3 months in vitro. In vivo, Paclimer implants placed intracranially in rats released active drug for up to 30 days after implantation and doubled the median survival of rats bearing established 9L gliosarcomas (median survival of paclitaxel-treated animals = 35 days; median survival of control-treated animal = 16 days; P < 0.0001). Active drug was distributed throughout the rat brain based on liquid scintillation counting and TLC. Rats implanted with Paclimer demonstrated no overt signs of neurotoxicity and exhibited local cytopathological changes consistent with exposure to an antimicrotubule agent. CONCLUSIONS: Paclimer extends survival in a rodent model of glioma with minimal morbidity and optimal pharmacokinetics.     

Comparative Diagnostic Utility of Low‐Dose Breast‐Specific Gamma Imaging to Current Clinical Standard

To retrospectively compare low‐dose (7–10 mCi) to high‐dose (15–30 mCi) breast‐specific gamma imaging (BSGI) in the detection of breast cancer. A retrospective review of 223 consecutive women who underwent BSGI exam between February 2011 and August 2013 with subsequent pathologic analysis was performed. Women were divided into low‐dose and high‐dose groups. The results of BSGI and pathology were compared, and the sensitivity, positive predictive value (PPV), and negative predictive value (NPV) were determined. A subgroup analysis was performed to evaluate specificity using benign follow‐up imaging to establish true‐negative results. There were 223 women who met inclusion criteria with 109 patients with 153 lesions in the low‐dose group and 114 patients with 145 lesions in the high‐dose group. Pathologic correlation demonstrates sensitivities of 97.6% (95% CI = 90.9–99.6%) and 94.6% (95% CI = 84.2–98.6%; p = 0.093), PPVs of 62.1% (95% CI = 53.2–70.3%) and 50.5% (95% CI = 40.6–60.3%, p = 0.089), and NPVs of 90.5% (95% CI = 68.2–98.3%) and 92.5% (95% CI = 78.5–98.0%, p = 0.781) in the low‐dose and high‐dose groups, respectively. Subgroup analysis included 72 patients with 98 lesions in the low‐dose group and 116 patients with 132 lesions in the high‐dose group, with a specificity of 53.7% (95% CI = 39.7–67.1%) and 66.3% (95% CI = 56.2–75.2%%, p = 0.143), respectively. Low‐dose BSGI demonstrated high sensitivity and NPV in the detection of breast cancer comparable to the current standard dose BSGI, with moderate specificity and PPV in a limited subgroup analysis, which was associated with a substantial number of false‐positives.     

Clinical application of growth factors and cytokines in wound healing

Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous growth factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various growth factors in the clinical management of nonhealing wounds (e.g., pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted an online search of Medline/PubMed and critically analyzed the literature regarding the role of growth factors and cytokines in the management of these wounds. We focused on currently approved therapies, emerging therapies, and future research possibilities. In this review, we discuss four growth factors and cytokines currently being used on and off label for the healing of wounds. These include granulocyte‐macrophage colony‐stimulating factor, platelet‐derived growth factor, vascular endothelial growth factor, and basic fibroblast growth factor. While the clinical results of using growth factors and cytokines are encouraging, many studies involved a small sample size and are disparate in measured endpoints. Therefore, further research is required to provide definitive evidence of efficacy.