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.     

Quantitative real-time PCR detection of adenovirus in clinical blood specimens: A comparison of plasma, whole blood and peripheral blood mononuclear cells

BACKGROUND: Detection and quantification of adenovirus (ADV) in peripheral blood specimens has become an increasingly important tool in the management of immunosuppressed patients. Investigators have described the use of whole blood (WB), peripheral blood mononuclear cells (PBMC), serum and plasma but no studies have compared the utility of these different sample types for use in a clinical diagnostic assay. OBJECTIVES: To determine the optimal blood compartment for quantitative real-time measurement of adenovirus in peripheral blood specimens. STUDY DESIGN: WB, PBMC, and plasma representing 338 samples from 148 patients were tested for ADV by quantitative real-time PCR (qrt-PCR) and the results compared for concordance of both qualitative sensitivity and viral load among positive specimens. RESULTS: There was no significant difference in qualitative sensitivity among the three tested specimen types. Quantitative values of WB and plasma were similar and tended to be greater than those found in PBMC samples. Comparison of consecutive positive samples within individual patients showed that viral loads tracked similarly over time, irrespective of the sample type tested. CONCLUSION: While WB and plasma do not offer a significant increase in sensitivity over PBMC, they may offer benefits in terms of reduced processing costs and laboratory turn around time.     

Neuropharmacological assessment of potential dopamine D4 receptor-selective radioligands

Radiolabeled dopamine D4 receptor-selective agents ([3H]1-benzyl-4-[ N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine maleate; [3 H]PNU-101958. and [125I]1-[4-iodobenzyl]-4-[ N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine; [125I]RBI-257) were prepared and characterized. With D4.2- and D2L receptor-transfected cell membranes, [3H]PNU-101958 showed high dopamine D4 receptor affinity and selectivity, and potent inhibition by dopamine D4 receptor-selective compounds. However, its binding with rat brain homogenates showed little regional selectivity, and pharmacology inconsistent with selective dopamine D4 receptor labeling. Autoradiography indicated partial displacement of [3H]PNU-101958 by unlabeled dopamine D4 receptor ligands without regional selectivity, and lack of selective labeling with [125I]RBI-257. The results encourage further efforts to develop better dopamine D4 receptor-selective radioligands.     

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.     

Outcomes of upper extremity interventions for chronic critical ischemia

Background

Critical hand ischemia owing to below-the-elbow atherosclerotic occlusive disease is relatively uncommon. The aim of this study was to examine the outcomes in patients presenting with critical ischemia owing to below-the-elbow arterial atherosclerotic disease who underwent nonoperative and operative management.

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.