Improving care through standardized treatment of spontaneous pneumothorax

PurposeThe objective of this quality improvement (QI) initiative was to implement a standardized clinical treatment protocol for patients presenting with primary spontaneous pneumothorax (PSP) in order to decrease hospital length of stay (LOS), diagnostic radiation exposure, and related cost.MethodsBaseline data from patients admitted with PSP from January 1, 2016 to July 31, 2018 were compared to data from patients managed using a newly developed evidence-based treatment pathway from August 1, 2018 to December 31, 2019. Standard QI methodology was used to track results.ResultsFifty-six episodes of PSP were observed during the baseline period and 40 episodes of PSP following initiation of the PSP protocol. The average LOS decreased from 4.5 days to 2.9 days. Patients underwent an average of 8.8 X-rays per admission preintervention versus 5.9 postintervention. The rate of CT scans decreased from 45% to 15% (p = 0.002). There was no significant difference in the rates of 30-day recurrence between the preintervention (13%) and postintervention (10%) groups (p = 0.7). Average admission costs per patient decreased by $1322 after adoption of the pathway.ConclusionsAdoption of a standardized treatment protocol for PSP led to a reduction in LOS, diagnostic imaging utilization, and cost without increasing clinical recurrence.Type of studyQuality improvement.Level of evidenceLevel III.     

Single-donor fibrin glue for hand burns

Early tangential excision sometimes results in considerable blood loss, prolonged operative time, and partial loss of the graft secondary to hematoma formation. Previous reports document positive hemostatic effects and improved skin fixation with fibrin "glue." The commercial preparation used in Europe, however, has not been approved by the United States Food and Drug Administration because of the high risk of hepatitis and human immunodeficiency virus transmission. Using a method developed at the University of Virginia, we applied single-donor fibrin glue as an adjunct in early excision and grafting in 16 patients (26 hands). The overall graft take was 99%. In all patients, better adherence of the split-thickness graft to the recipient bed, during and immediately after application, was noted. We have observed no negative effects with regard to infection or healing. We recommend the use of single-donor fibrin glue to reduce operative blood loss, improve survival and ease of graft application, and possibly to accelerate healing.     

Analysis of gene expression in human bullous keratopathy corneas containing limiting amounts of RNA

PURPOSE: To validate the use of polymerase chain reaction (PCR)-amplified full-length cDNA as a substitute for mRNA in nucleic acid array and gene expression analysis. METHODS: Total RNA was isolated from age-matched normal autopsy corneas and pseudophakic bullous keratopathy (PBK) corneas. Full-length cDNA was generated and PCR amplified using the Smart cDNA synthesis technology. Southern blot analysis of this cDNA was compared with Northern blot analysis of the RNA. Amplified cDNA was used to probe a commercial gene array. By immunohistochemistry, the expression pattern of several adhesion molecules represented on the array was assessed. RESULTS: The cDNA produced by the Smart cDNA system gave results very similar to those of northern blot analysis when examined for beta2-microglobulin, Rab geranylgeranyl transferase, and tenascin-C. This cDNA obtained from normal or PBK corneas was labeled and used to probe a 588 gene array (Clontech). Among other differences, beta6 integrin was detected only with the PBK probe, beta-catenin was markedly elevated in PBK, and beta4 integrin appeared to be reduced in PBK. Immunohistochemical patterns of these proteins were consistent with the hybridization signals on the gene array. CONCLUSIONS: Smart cDNA synthesis and nucleic acid arrays were combined and validated for the first time to identify differential gene expression in normal and diseased corneas. These techniques require very little RNA such as that equivalent to a half of a single cornea, which is useful when the amount of tissue is limiting. Altered expression of adhesive proteins beta6 integrin and beta-catenin may be related to the formation of epithelial bullae and microcystic changes in PBK patients.     

Selective toxicity of the tricyclic thiophene NSC 652287 in renal carcinoma cell lines: differential accumulation and metabolism

The tricyclic compound 2,5-bis(5-hydroxymethyl-2-thienyl)furan (NSC 652287) has shown a highly selective pattern of differential cytotoxic activity in the tumor cell lines comprising the National Cancer Institute (NCI) Anticancer Drug Screen. The mechanism underlying the selective cytotoxicity is unknown. We hypothesized that differential sensitivity to the compound observed in several renal tumor cell lines could be the result of selective accumulation or differential metabolism of this agent. We demonstrated here that the capacity of certain renal cell lines to accumulate and retain the compound, determined by accumulation of [14C]NSC 652287-derived radioactivity and by flow cytometric determination of unlabeled compound, paralleled the sensitivity of the renal cell lines to growth inhibition by NSC 652287: A-498 > TK-10 > ACHN approximately/= to UO-31. The ability of the cell lines to metabolize [14C]NSC 652287 to a reactive species capable of binding covalently to cellular macromolecules also directly correlated with sensitivity to the compound. Different patterns of metabolites were generated by relatively more drug-sensitive cell lines in comparison with drug-resistant cell lines. The metabolizing capacity for NSC 652287 was localized primarily to the cytosolic (S100) fraction. The rate of metabolism in the cytosolic fraction from the most sensitive renal cell line, A-498, was faster than that observed in the cytosolic fractions from the other, less sensitive cell lines. The data support the hypothesis that both selective cellular accumulation and the capacity to metabolize NSC 652287 to a reactive species by certain renal carcinoma cell types are the basis for the differential cytotoxicity of this compound class.     

Anomalies of centriolar derivatives manifest in spermatic flagella and respiratory cilia of the stallion.

Anomalies of centriolar derivatives were identified in ejaculates and testicular and tracheal biopsies of a sterile stallion, using light, scanning, and transmission electron microscopy. LM revealed that over half the sperm population had only a vestigial or no tail, while the rest had tails of variable length and shape. The vestigial tail was represented by its anlage, which was implanted on the nucleus and differentiated up to capitulum and collum stage. The stunted tail had an axoneme and its derivatives, but was short in all tail segments. Regardless of the tail length or shape, virtually all axonemes were devoid of the central tubular complex ("9 + 0" defect). Abnormal tail segmentation was associated with missing or defective flagellar sheaths and a profusion of extraneous dense fibers, which contributed to the knobby, bulbous, or lobuliform tail configurations. The gradient of flagellar anomalies seems associated with the inability of the distal centriole to implant on the plasmalemma, to produce the axoneme, or maintain its growth, and to induce the normal differentiation of periaxonemal structures. In contrast to sperm, the tracheal epithelium displayed moderate changes, which are manifest in circumscribed rarefaction of cilia, increased incidence of compound cilia, and disturbed orientation of cilia regarding the plane of central tubular complex. The tracheal cilia were free of "9 + 0" defect.     

Safety and efficacy of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. multicenter phase III clinical trials (safety)

The short-term safety of mangafodipir trisodium (MnDPDP) injection was studied in 546 adults with known or suspected focal liver lesions. An initial contrast-enhanced computed tomography examination was followed by unenhanced magnetic resonance imaging (MRI), injection of MnDPDP (5 micromol/kg), and enhanced MRI. Adverse events were reported for 23% of the patients; most were mild to moderate in intensity, did not require treatment, and were not drug related. The most commonly reported adverse events were nausea (7%) and headache (4%). The incidence of serious adverse events was low (nine events in six patients) and not drug related. Injection-associated discomfort was reported for 69% of the patients, and the most commonly reported discomforts included heat (49%) and flushing (33%). Changes in laboratory values and vital signs were generally transient, were not clinically significant, and did not require treatment. There were no clinically significant short-term risks from exposure to MnDPDP.     

A delayed onset of haloperidol effects on learned escape and avoidance behavior

The effects of 0.3 mg/kg haloperidol (H) on the acquisition and maintenance of footshock escape behavior of rats in a one meter runway was investigated. In the acquisition phase, a group (N = 6) given H before testing (HB) showed severely retarded acquisition and performance of the escape response, as compared with a group (N = 6) given H after testing (HA). When the HB and HA treatments were reversed for the groups behavioral performance was initially unaffected. At first, the HA group switched to the HB condition continued to exhibit rapid escape behavior and the HB group switched to the HA treatment continued to have slow escape behavior. Over the course of 8 days of testing, however, the performances of the two groups gradually reversed. After completion of this testing the HB and HA treatments again were switched and the animals were tested for both avoidance and escape behavior. Again, the performance of the animals initially did not change after the treatment switch, but with repeated testing and treatments, the avoidance and escape behavior of the HB group slowed substantially and that of the HA group accelerated markedly. These findings support previous observations that over learned behaviors are much less sensitive to disruption by haloperidol treatment than behaviors which are undergoing learning. The important contribution of the present study was in demonstrating that this insensitivity is a transitional, transient phenomenon and that with chronic treatment and testing, over learned behaviors can be strongly affected by haloperidol.(ABSTRACT TRUNCATED AT 250 WORDS)     

维A类化合物4-APR抑制肿瘤侵袭、转移的作用

用体内外实验模型,研究了新维A类化合物4-乙酰胺苯基维A酸酯(4-APR)对肿瘤侵袭、转移的抑制作用。4-APR 43.3mg·kg^-1po即能减少小鼠Lewis肺癌的自发性肺转移瘤数。半体内实验证明4-APR10^-5mol·L^-1和10^-6mol·L^-1对B16-F10癌细胞的人工肺转移瘤数分别抑制67.9%和36.6%。体外实验显示,4-APR对B16-F10细胞侵袭重组基底膜的抑制率分别为54.2%和41.9%。     

Induction of protective immunity against lethal anthrax challenge with a patch

BACKGROUND: Transcutaneous immunization (TCI) is a needle-free technique that delivers antigens and adjuvants to potent epidermal immune cells. To address critical unmet needs in biodefense against anthrax, we have designed a novel vaccine delivery system using a dry adhesive patch that simplifies administration and improves tolerability of a subunit anthrax vaccine. METHODS: Mice and rabbits were vaccinated with recombinant protective antigen of Bacillus anthracis and the heat-labile toxin of Escherichia coli. Serologic changes, levels of toxin-neutralizing antibodies (TNAs), and pulmonary and nodal responses were monitored in the mice. A lethal aerosolized B. anthracis challenge model was used in A/J mice, to demonstrate efficacy. RESULTS: The level of systemic immunity and protection induced by TCI was comparable to that induced by intramuscular vaccination, and peak immunity could be achieved with only 2 doses. The addition of adjuvant in the patch induced superior TNA levels, compared with injected vaccination. CONCLUSIONS: Anthrax vaccine patches stimulated robust and functional immune responses that protected against lethal challenge. Demonstration of responses in the lung suggests that a mechanism exists for protection against challenge with aerosolized anthrax spores. A formulated, pressure-sensitive, dry adhesive patch, which is stable and can be manufactured in large scale, elicited comparable immunoglobulin G and TNA responses, suggesting that an anthrax vaccine patch is feasible and should advance into clinical evaluation.