Sustaining better care for patients undergoing emergency laparotomy.

Emergency laparotomy is associated with high mortality. Implementation of an evidence-based care bundle has been shown to improve patient outcomes. A quality improvement project to implement a six-component care bundle was undertaken between July 2015 and May 2018. As part of this project, we worked with 27 hospitals in the Emergency Laparotomy Collaborative. Previous pilot implementation of the same bundle in our hospital between December 2012 and July 2013 had shown marked improvement, maintained until April 2014, but then deterioration. Understanding the reasons for this deterioration informed our work to re-implement the bundle and sustain improvement. A cohort of 930 consecutive patients requiring emergency laparotomy between October 2014 and April 2019 were included. Baseline data were collected between October 2014 and June 2015, and the bundle was re-implemented in July 2015. Thirty-day mortality decreased from 11% in the baseline group to 7.3% after bundle implementation. Hospital length of stay decreased from 19.5 to 17.9 days. Full bundle compliance improved from < 60% to > 80% for all patients, with improvement in application of all individual bundle components. This study provides further evidence that outcomes for high-risk surgical patients can be improved with an evidence-based care bundle, but attention must be paid to maintaining bundle compliance. Issues around sustaining improvement must be considered from project initiation.

X-ray spectroscopy studies on the surface structural characteristics and electronic properties of platinum nanoparticles.

The surface structural characteristics and electronic behavior of three platinum nanoparticle (NP) samples prepared with tertiary amine (Pt-TA), primary amine (Pt-PA), and thiol (Pt-SR) molecules were studied using Pt 4f, 5d, and S 2p x-ray photoelectron spectroscopy (XPS), Pt L(3)-edge x-ray absorption spectroscopy (XAS), and theoretical projected local density of states (l-DOS) calculations. Transmission electron microscopy and XPS composition analysis indicated that the three NPs were all very small (1-2 nm), the NP size decreasing in the order of Pt-TA>Pt-PA approximately Pt-SR. All the three samples showed a positive Pt 4f binding energy (BE) shift relative to that of the bulk, in the order of bulk

Surface structural characteristics and tunable electronic properties of wet-chemically prepared Pd nanoparticles.

The ligand substitution reaction, Pd L(3,2,1)-edge and S K-edge x-ray absorption fine structure (XAFS), XAFS simulations, and valence-band and core-level x-ray photoelectron spectroscopy (XPS) have been used to systematically study the surface chemical and electronic properties of wet-chemically prepared Pd nanoparticles of varied size, molecular capping, and metal composition. It was found that the replacement of weakly interacting capping molecules (amine and tetra-alkylphosphonium bromide) with strongly binding thiols caused a considerable change in the surface bonding of Pd nanoparticles. However, the Pd d-electron counts (number of d electrons) remained almost unchanged before and after ligand substitution, which is unexpected since Pd atoms normally lose electrons to the more electronegative S atoms. XAFS results and simulations provided useful insights into the surface structural characteristics of Pd nanoparticles and satisfactorily accounted for the unexpected d-electron behavior involved in the ligand substitution process. XPS valence and core-level spectra further revealed a size-dependent d-band narrowing and presented complementary information to XAFS about the surface electronic properties of Pd atoms. The small weakly bound Pd nanoparticles seem inevitably to have a net d-electron depletion due to the influence of the surface effect (chemical adsorption by oxygen), which is more significant than the d-electron enriching nanosize effect. However, it was demonstrated that by forming Pd-Ag alloy nanoparticles, a net increase of the Pd d-electron counts can be realized. Therefore, it is illustrated that by manipulating the surface, size, and alloying effects, the electronic properties of Pd nanoparticles can be possibly tuned.

Development and validation of a reverse-phase HPLC method for analysis of efavirenz and its related substances in the drug substance and in a capsule formulation.

A stability-indicating high performance liquid chromatographic (HPLC) method was developed for the assay of efavirenz, a non-nucleoside reverse transcriptase inhibitor used in the treatment of AIDS. The HPLC method, which is used to determine potency in efavirenz capsules and related substances in efavirenz drug substance and capsules, was validated per ICH guidelines. This method, which uses a cyano column, is capable of separating efavirenz from its trans-alkene reduction product. This paper will discuss development and validation of this method, which, to the best of our knowledge, is the first known separation of homologs containing double and triple bonds using reverse-phase HPLC.

Validation of cleaning procedures for highly potent drugs. II. Bisnafide.

The objective of this work was the development and validation of procedures designed to clean glass and stainless steel surfaces after exposure to the experimental anticancer drug, bisnafide. The cleaning procedures, using 5% acetic acid water, Alconox, and water, were validated using a wipe test and an HPLC method developed to quantitate low levels of bisnafide. The procedure developed for cleaning stainless steel is more stringent than that for glass because of the apparent greater affinity of bisnafide for stainless steel. The HPLC method is shown to be linear and reproducible (RSD 4.4% or less), with a detection limit of 4 ng/ml. Recoveries of 95.1, 83.5, and 70.0% were obtained from the wipe pads, glass plates, and stainless steel plates, respectively, at levels of approximately 0.7-1.7 ng/cm2. The cleaning procedures are shown to clean glass and stainless steel plates to less than 0.19 and 0.33 ng bisnafide/cm2, respectively. These results further demonstrate the need to fully characterize the recovery of drugs from surfaces and swabs in order to properly validate cleaning procedures. In addition, they demonstrate the potential need to develop surface-specific cleaning procedures.

Increased cell diameter precedes chondrocyte terminal differentiation, whereas cell-matrix attachment complex proteins appear constant.

BACKGROUND: Chondrocytes in specific areas of chick sterna have different developmental fates. Cephalic chondrocytes become hypertrophic and secrete type X collagen into the extracellular matrix, whereas middle and caudal chondrocytes remain cartilagenous throughout development, continuing to secrete collagen types II, IX, and XI. In this report, we ask if the cell size and cytoarchitecture of chondrocytes differ in cephalic, middle, and caudal portions of whole sterna prior to and during hypertrophy. In addition, what is the distribution of integrin subunits and actin associate proteins in differentiating chondrocytes? METHODS: Phalloidin was used to stain filamentous actin, and immunohistochemistry was used to localize the distribution of collagen molecules, integrin receptor subunits, and actin-associated proteins. RESULTS: Chondrocytes stained for filamentous actin demonstrated that on day 14 cephalic chondrocytes had a significantly larger diameter than middle and caudal chondrocytes. Day 17 chondrocytes in nonhypertrophic cephalic and middle regions of sterna were significantly smaller than hypertrophic chondrocytes and significantly larger than caudal chondrocytes. In contrast to day 14 chondrocytes, day 17 chondrocytes in the hypertrophic region demonstrated similar diameters at all cartilagenous depths. The beta 1 integrin subunit appeared punctate and associated with cell membranes, allowing nonpolarized interactions with extracellular matrix molecules. The distribution of alpha integrin subunits was similar to the beta 1 integrin subunit, although alpha integrin subunits also appeared cytoplasmic. Actin-associated proteins, vinculin, and alpha-actinin, were associated with F-actin, but vinculin was more specifically localized to the ends of the actin filaments. Focal adhesion kinase was diffusely distributed throughout the cytoplasm but also demonstrated areas of colocalization with vinculin. Zyxin and paxillin demonstrated a punctate distribution, although paxillin was slightly more diffuse. Using immunohistochemical detection, no difference in integrin subunit or actin associated protein distribution could be determined between chondrocytes and hypertrophic chondrocytes. CONCLUSIONS: The increased chondrocyte diameter observed in cephalic regions of sterna on day 14 suggests that intracellular changes may precede the specific hypertrophic marker, type X collagen, by several days. In addition, the presence of integrin subunits, which are known to interact with collagen and cytoskeletal proteins, suggests that communication may exist between chondrocytes and their extracellular matrix via these receptor molecules.

Forensic child and adolescent psychiatry.

This brief chapter has been written as an overview of child and adolescent forensic psychiatry. An attempt was made to briefly and simply summarize several topics. At the end of the chapter, the interested reader will find additional sources to pursue areas of interest in depth. Many important issues were not addressed, including aggression, homicide, the child as witness, countertransference issues, lesbian mothers and gay fathers, and dual-agency conflicts, among others. These and other issues are beyond the scope of this brief chapter, but nonetheless, important issues in forensic child and adolescent psychiatry. Forensic child and adolescent psychiatry is not for everyone. Those interested in working in the field will find it challenging. Beginners are urged to seek consultation from more experienced colleagues and the inexperienced practitioners will find consultation helpful. Although some may wish to avoid the forensic arena completely, those of us who work in the field find it rewarding.

Developmental patterns of expected consequences for simulated bicycle injury events.

Bicycle injuries follow a developmental pattern that differs from that of most injuries, where toddlers and individuals in young adulthood are most at risk. Children in late childhood and early adolescence appear most at risk for bicycle injuries. The present study of 2nd-grade, 4th-grade, 6th-grade, and undergraduate college students documented that after videotaped simulations of bicycle injury events, younger children anticipated greater injury severity and more fear than older children and adolescents. The potential influence of reduced expectations for injury with increasing age is described, and challenges are advanced for establishing the link between lowered injury expectancies and increased risky behavior.

Dose-proportional pharmacokinetics of cefepime in rats.

Cefepime (BMY-28142) is a new parenteral cephalosporin antibiotic with excellent activity against a broad-spectrum of clinically important pathogens resistant to other new cephalosporins. A single bolus dose of 10, 20 or 40 mg/kg cefepime was given i.v. to male and female Sprague-Dawley rats from which blood and urine samples were collected. For statistical reasons, pharmacokinetic parameters (AUC, Kel) were derived by fitting an exponential curve to the plasma concentrations; subsequently, contrasts were made between the different doses for AUC and Kel and, in addition, plasma concentrations observed after the first sampling time (Cmax). Cmax and AUC appeared to be linearly related to the administered dose in both males and females. The dose increased in the ratio 1:2:4 and mean Cmax in male and female rats increased in the ratio 1:2.3:4.1 and 1:2.3:4.4 respectively; similarly, AUC increased in the ratio 1:2.2:4.3 and 1:2.0:4.2 respectively. Deviations from linearity and proportionality were not significant (P0.05). The systemic clearance of cefepime in rats was 2.3 ml/min. The volume of distribution was about 60 ml and cefepime appears to be selectively distributed into the extracellular water. Plasma concentrations declined monoexponentially with a mean half-life of 15-20 min which did not significantly change with increasing doses. The renal clearance of cefepime was 1.8 ml/min and approximately 80% of the dose was excreted in the urine unchanged; renal excretion of cefepime is the major route of elimination in rats. The elimination and distribution characteristics of cefepime in rats were similar to those observed in man.

A highly conserved, 5' untranslated, inverted repeat sequence is ineffective in translational control of the alpha 1(I) collagen gene.

An inverted repeat sequence, extending from the 5' untranslated region of the first exon through the translation initiation codon, is highly conserved in the alpha 1(I), alpha 2(I) and alpha 1(III) collagen genes of mammals and birds. It has been suggested that this sequence functions in translational control of collagen gene expression. When the upstream axis of the dyad of symmetry was deleted, the efficiency of translation of transcripts from a human alpha 1(I) collagen-bovine growth hormone fusion gene was unchanged in either transiently or stably transfected cells. Furthermore, mRNA levels were not affected when the same deletion was transferred to a collagen-human growth hormone fusion gene in which the collagen sequence retained the first intron. Examination of human alpha 1(I) DNA, extending from the start of transcription to the start of translation, by the DNAse I protection procedure revealed evidence for protein binding to a sequence just upstream of the inverted repeat sequence but not to the inverted repeat itself. Our studies therefore indicate that this highly conserved DNA sequence does not function generally in translational or transcriptional control of type I procollagen synthesis.

Control of smooth muscle cell growth by components of the extracellular matrix: autocrine role for thrombospondin.

Addition of platelet-derived growth factor (PDGF) to growth-arrested cultured smooth muscle cells (SMC) induces the synthesis and secretion of thrombospondin (TS), a glycoprotein component of the SMC extracellular matrix in vitro. This induction occurs at PDGF concentrations that are suboptimal for a mitogenic response. In this study we examined the effect of TS on the proliferation of SMC, using a serum-free mitogenesis assay. Addition of either epidermal growth factor (EGF) or purified human platelet TS to quiescent rat vascular SMC did not substantially stimulate mitogenesis; the 30-hr nuclear labeling index increased from a mean of 7% in control cells to 20% for EGF-treated SMC and 17% for cells exposed to TS alone. However, TS and EGF acted synergistically to stimulate DNA synthesis by SMC, increasing the labeling index to 47%. The facilitative effect of TS on EGF-mediated mitogenesis was inhibited by heparin, a known inhibitor of SMC growth and migration that also blocks incorporation of TS into the SMC extracellular matrix. The effect was specific for EGF; TS did not augment the response of cells to insulin or insulin-like growth factor 1. These data establish a functional role for cell-derived TS and provide evidence for the presence of an autocrine, growth-supportive mechanism involving the extracellular matrix. In addition, our experiments support the existence of a novel, heparin-sensitive SMC mitogenic pathway and suggest a mechanism whereby heparin-like molecules may inhibit SMC proliferation.

Platelet-derived growth factor and heparin-like glycosaminoglycans regulate thrombospondin synthesis and deposition in the matrix by smooth muscle cells.

Platelet-derived growth factor (PDGF), a smooth muscle cell (SMC) mitogen, and heparin-like glycosaminoglycans, known inhibitors of SMC growth and migration, were found to regulate thrombospondin synthesis and matrix deposition by cultured rat aortic SMC. The synthesis and distribution of thrombospondin was examined in growth-arrested SMCs, in PDGF-stimulated SMCs, and in heparin-treated SMCs using metabolic labeling and immunofluorescence techniques. Thrombospondin synthesis in response to purified PDGF occurred within 1 h after addition of growth factor to growth-arrested SMCs, peaked at 2 h, and returned to baseline levels by 5 h. The induction of synthesis of thrombospondin by PDGF was dose dependent, with a maximal effect observed at 2.5 ng/ml. Actinomycin D (2 micrograms/ml) inhibited thrombospondin induction by PDGF, suggesting a requirement for new RNA synthesis. In the presence of heparin and related polyanions, the incorporation of thrombospondin into the SMC extracellular matrix was markedly reduced. This effect was dose dependent with a maximal effect observed at a heparin concentration of 1 microgram/ml. Heparin did not affect the ability of SMCs to synthesize thrombospondin in response to PDGF. We interpret these data to suggest a role for thrombospondin in the SMC proliferative response to PDGF and in the regulation of SMC growth and migration by glycosaminoglycans.

[Bioavailability of isosorbide-5-mononitrate from delayed-action formulations]. / Freisetzung von Isosorbid-5-mononitrat aus Retard-Formulierungen.

The relative bioavailability of isosorbide-5-mononitrate (IS-5-MN) has been determined after a 3-day period of dosing with 20 mg in standard-release reference tablets and sustained-release capsules at 12-h intervals, 40 mg in sustained-release capsules (Olicard 40 retard) at 24-h intervals and after single oral dose of 60 mg sustained-release capsules (Olicard 60 retard), in a cross-over study with 12 human subjects. Accumulation factors of 1.1-fold or 1.2-fold occurred during administration of 20 mg in standard- or sustained-release tablets and capsules respectively at 12-h intervals, and negligible accumulation of drug occurred after administration of 40 mg in sustained-release capsules at 24-h intervals or was calculated by the superposition principle to occur after doses of 60 mg in sustained-release capsules at 24-h intervals. The mean extent of bioavailability of IS-5-MN from the 20 mg, 40 mg and 60 mg sustained-release capsules was 79%, 67% and 70% respectively, of that from the standard-release reference tablets. The posterior probability that the bioavailability of IS-5-MN was included within the limits 60%-90% of the reference tablets was 97%, 86% and 95% for the 20 mg, 40 mg and 60 mg sustained-release capsules respectively. Means of peak plasma levels of IS-5-MN after administration of the sustained-released capsules were linearly related to the doses administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of the Children's Depression Rating Scale in an inpatient psychiatric population.

The Children's Depression Rating Scale is a useful and reliable instrument for measuring the severity of depression in children. The scale was initially used in a pediatric liaison population. This study reports its use in consecutive admissions to a child inpatient unit. Systematic evaluations of the children resulted in many diagnoses of depression which were missed by the clinical staff. Two relatively inexperienced raters did nearly as well as two raters who originated the scale, suggesting that the CDRS may have practical utility in many settings.

The dexamethasone suppression test in prepubertal depressed children.

The authors evaluated 18 dysphoric children aged 6--12 years by structured clinical assessments and an overnight dexamethasone suppression test (DST) administered on an outpatient basis. Nine children met diagnostic criteria for major depressive disorder, and 8 of the 9 also met the Research Diagnostic Criteria for endogenous depression. Of the 9 depressed children, 5 had abnormal DST results; 8 of the 9 nondepressed children had normal test results. The results suggest that endogenous depression in childhood is not a rare condition and that it is clinically and neuroendocrinologically similar to the adult disorder. The DST may be useful as a diagnostic aid with depressed children.

A depression rating scale for children.

A rating scale is needed for clinical and research studies of depression in childhood. A Children's Depression Rating Scale (CDRS) was devised and tested on 30 inpatient children in a medical hospital. A high correlation was found between the global ratings by two psychiatrists of the severity of depression and the scores on the CDRS. The items on the CDRS which had the highest correlation with a global rating of depression were social withdrawal, capacity for fun, irritability, schoolwork, expressive communication, general somatic features, hypoactivity, and depressed mood. The syndrome of depression in childhood can be characterized and rated primarily by observed behaviors.