Transdermal microconduits by microscission for drug delivery and sample acquisition

Background  

Painless, rapid, controlled, minimally invasive molecular transport across human skin for drug delivery and analyte acquisition is of widespread interest. Creation of microconduits through the stratum corneum and epidermis is achieved by stochastic scissioning events localized to typically 250 μm diameter areas of human skin in vivo.     

MILITANCY TRAUMA : MAXILLOFACIAL INJURY,ANAESTHESIA AND CRITICAL CARE

Eighty four out of 2151 militancy trauma patients sustained severe maxillofacial injury from Jan 1990 to March 1993. The resuscitation, stabilisation and intensive care of these patients was based on management priorities of primary resuscitation, care of airway, management of haemodynamics, oxygenation and monitoring. Anaesthesia was administered in a situation when the airway was likely to be compromised and the patients were critically sick. Initial ventilation and oxygenation was the most difficult and could be achieved with satisfactory seal around the face mask by applying water-soaked guaze pieces around the mouth and nose to “fill-in” the defects. Tracheal intubation could be accomplished with intravenous sedation by an experienced anaesthesiologist. Dental occlusion and wiring necessiated the placement of nasotracheal tube for 48-72 hours after surgery.KEY WORDS: Trauma, Maxillofacial injury, Trauma anesthesia, Anaesthesia and critical care     

Actuarial survival in the premature infant less than 30 weeks' gestation

OBJECTIVE: Because survival from admission to discharge does not provide parents and physicians information about future life expectancy in the premature neonate, we characterized the actuarial survival, defined as the future life expectancy from a given postnatal age, in a large inborn population of premature infants < 30 weeks' gestation. STUDY DESIGN: We determined daily actuarial survival of 1925 inborn infants (23 to 29 weeks' gestation) admitted to the Baylor Affiliated Nurseries from July 1986 through December 1994, stratified by 100-g birth weight and by 1-week gestational-age intervals. RESULTS: In the 501- to 600-g birth weight stratum, actuarial survival improved from 31% at birth, to 61% on day of life 7, and then to 75% on day of life 28; in the 901- to 1000-g birth weight stratum, actuarial survival improved from 88%, to 94%, and then to 98% throughout the same times, respectively. Similar trends were obtained when data were stratified by gestational age. CONCLUSIONS: Survival in the smallest infants improves dramatically during the first few days of life, but there is a significant risk for late death in the smallest of these infants.     

用正糖钳夹试验评估基础胰岛素类似物作用特点的研究

健康人通过体内胰岛素的分泌调节，可以保持正常的血糖水平。各种外源性胰岛素制剂在代谢过程上总是尽可能地模拟内源性胰岛素的分泌动力学。理想的外源性基础胰岛素制剂可以模拟健康人的基础胰岛素分泌，以致使用者可以恢复两餐之间和夜间正常生理情况下的血浆胰岛素水平。     

Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte hyperplasia in mice

PEG-rHuMGDF injected daily in normal mice causes a rapid dose-dependent increase in megakaryocytes and platelets. At the same time that platelet numbers are increased, the mean platelet volume (MPV) and platelet distribution width (PDW) can be either decreased, normal, or increased depending on the dose and time after administration. Thus, PEG-rHuMGDF at a low dose causes decreases in MPV and PDW, MGDF at an intermediate dose causes an initial increase followed by a decrease in MPV and PDW, and PEG-rHuMGDF at higher doses causes an increase in MPV and PDW followed by a gradual normalization of these platelet indices. In addition to the expected thrombocytosis after 7 to 10 days of daily injection of high doses of PEG-rHuMGDF, a transient decrease in peripheral red blood cell numbers and hemoglobin is noted accompanied in the bone marrow by megakaryocytic hyperplasia, myeloid hyperplasia, erythroid and lymphoid hypoplasia, and deposition of a fine network of reticulin fibers. Splenomegaly, an increase in splenic megakaryocytes, and extramedullary hematopoiesis accompany the hematologic changes in the peripheral blood and marrow to complete a spectrum of pathologic features similar to those reported in patients with myelofibrosis and megakaryocyte hyperplasia. However, all the PEG-rHuMGDF-initiated hematopathology including the increase in marrow reticulin is completely and rapidly reversible upon the cessation of administration of PEG-rHuMGDF. Thus, transient hyperplastic proliferation of megakaryocytes does not cause irreversible tissue injury. Furthermore, PEG-rHuMGDF completely ameliorates carboplatin-induced thrombocytopenia at a low-dose that does not cause the hematopathology associated with myelofibrosis.     

Expression of an anti‐RNA autoantibody in a mouse model of SLE increases neutrophil and monocyte numbers as well as IFN‐I expression

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of antinucleic acid autoantibodies, high levels of circulating type I interferon (IFN‐I), and an IFN‐I‐dependent elevated expression of activating FcγR. Increases in neutrophils and monocytes are often observed in clinical SLE, but how these contribute to autoantibody and IFN‐I production is poorly understood. Here, we analyzed SLE pathogenesis in 564Igi mice, an SLE‐model strain carrying gene‐targeted heavy and light chain antibody genes encoding an anti‐RNA autoantibody in a C57BL/6 background. Similar to human SLE patients, 564Igi mice produce anti‐RNA autoantibodies and expanded neutrophil and monocyte populations. These myeloid cells produced IFN‐I and exhibit increased FcγRIV expression induced via an IFN‐I autocrine loop. A direct effect of IFN‐I on 564Igi BM B cells and neutrophils was supported by their upregulation of “IFN‐I signature genes”. In addition, 564Igi developing B cells showed upregulated TLR7 resulting in IgG2a/2b class switch recombination and autoantibody production. Our results indicate that the production of anti‐RNA autoantibody is sufficient to induce an increase of BM, blood, and spleen IFN‐I‐producing neutrophils, and suggest a mechanism by which autoantibody and IFN‐I contribute to SLE by activating B lymphocytes, neutrophils, and monocyte effector cells in vivo.