Influence of gender,BMI and body shape on theoretical injection outcome at the ventrogluteal and dorsogluteal sites

Aims and objectives

This study aimed to determine the influences of gender, BMI and observed body shape on subcutaneous fat and muscle thicknesses, and theoretical injection outcome, at the ventrogluteal and dorsogluteal intramuscular injection sites.

Background

Debate continues as to whether the dorsogluteal or ventrogluteal injection site is more reliable for a successful intramuscular injection outcome. Subcutaneous fat and muscle thicknesses at the injection site are direct determinants of intramuscular injection outcome. BMI and observed body shape influence gluteal subcutaneous fat and muscle thicknesses, and therefore injection outcome, with potentially distinct effects at the ventrogluteal and dorsogluteal sites.

Design

This was a cross‐sectional study.

Methods

Demographic data were collected, and subcutaneous fat and muscle thicknesses were quantified bilaterally at the dorsogluteal and ventrogluteal injection sites using ultrasound, for 145 participants (57% female).

Results

Subcutaneous fat and muscle were significantly thicker at the dorsogluteal than the ventrogluteal site, and 75% and 86% of participants would receive a successful intramuscular injection at these sites, respectively. There were significant effects of gender, BMI and observed body shape on subcutaneous fat thickness and theoretical injection outcome at both sites. Females, obese individuals and endomorph individuals had thicker subcutaneous fat and were more likely to have a subcutaneous injection outcome.

Conclusions

Gender, BMI and observed body shape could be used to guide site and needle length selection when administering gluteal intramuscular injections to increase the likelihood of a successful intramuscular injection outcome.

Relevance to clinical practice

Both gluteal injection sites should be avoided in obese individuals and endomorph individuals. An intramuscular injection will be successful: using a 32‐mm needle at the ventrogluteal site for all males and normal‐weight females and using a 38‐mm needle for all females at the ventrogluteal site, and for all males and at least 98% of females at the dorsogluteal site.     

B19 parvovirus replicates in circulating cells of acutely infected patients

B19 parvovirus is the etiologic agent of fifth disease and transient aplastic crisis. In natural infections, B19 antigen and DNA have been detected in sera early in the course of aplastic crisis and only rarely in fifth disease. We have found B19 DNA in circulating cells of infected patients by DNA dot blot with a virus-specific probe: in four of four sickle cell patients with aplastic crisis, in one asymptomatic sibling, and in one normal adult with fifth disease. Only two of the sera showed B19 DNA. High-molecular weight intermediate forms were detected by Southern analysis of DNA extracted from cells, thus indicating active replication of virus in cells rather than passive adsorption to their surface membranes. Separation of cells into high- and low-density fractions resulted in a concentration of the virus DNA in the granulocytic fraction.     

Early volatile depletion on planetesimals inferred from C–S systematics of iron meteorite parent bodies

During the formation of terrestrial planets, volatile loss may occur through nebular processing, planetesimal differentiation, and planetary accretion. We investigate iron meteorites as an archive of volatile loss during planetesimal processing. The carbon contents of the parent bodies of magmatic iron meteorites are reconstructed by thermodynamic modeling. Calculated solid/molten alloy partitioning of C increases greatly with liquid S concentration, and inferred parent body C concentrations range from 0.0004 to 0.11 wt%. Parent bodies fall into two compositional clusters characterized by cores with medium and low C/S. Both of these require significant planetesimal degassing, as metamorphic devolatilization on chondrite-like precursors is insufficient to account for their C depletions. Planetesimal core formation models, ranging from closed-system extraction to degassing of a wholly molten body, show that significant open-system silicate melting and volatile loss are required to match medium and low C/S parent body core compositions. Greater depletion in C relative to S is the hallmark of silicate degassing, indicating that parent body core compositions record processes that affect composite silicate/iron planetesimals. Degassing of bare cores stripped of their silicate mantles would deplete S with negligible C loss and could not account for inferred parent body core compositions. Devolatilization during small-body differentiation is thus a key process in shaping the volatile inventory of terrestrial planets derived from planetesimals and planetary embryos.

Major volatiles (H, C, N, and S) are inherently plentiful in the interstellar medium and abundant in primitive carbonaceous chondrites (CCs) (1, 2), but are scarce in terrestrial planets, which gained most of their mass from the inner parts of the solar nebula (3, 4). Formation of volatile-poor planets from a volatile-rich protoplanetary disk is a result of processes in the solar nebula, in accretion of precursor solids, and in interior differentiation. Addition of volatiles to nascent planets varies during accretion as protoplanetary systems become dynamically excited, contributing material originating from different heliocentric distances (3) and with different thermal histories. Much of this mass arrives in larger bodies (planetesimals or planetary embryos) that differentiated soon after formation (5). Key uncertainties include the nebular history of bulk materials that contributed volatiles to the rocky planets and how that affected their volatile cargos (6), and how planetesimal and planet formation influenced volatile distributions in accreted parent bodies.Processes responsible for volatile deficits in terrestrial planets (7, 8) can occur either in the nebular, planetesimal, or planetary environment. Nebular volatile depletion could result from chemical interactions between nebular gas and dust, chondrule formation, or the accretion of thermally processed solids (9–11), perhaps owing to the hotter conditions prevailing closer to the protosun (4). Li et al. (6) argue that the comparatively small C inventory of the bulk Earth requires that nebular materials experienced significant early (<1 Ma) heating, before the “soot line” moved inward of 1 AU. Planetesimal processes involve loss to space during differentiation or processing of intermediate-sized bodies of tens to hundreds of kilometers in diameter (e.g., refs. 12 and 13). Planetary loss processes occur on large (thousands of kilometers in diameter) bodies (14, 15) in which gravity plays an appreciable role—including loss from impacts (16). The sum of these is an important determinant for whether terrestrial planets form with volatiles sufficient for habitability but not so great as to become ocean worlds (17) or greenhouse hothouses (18).A key goal in the study of exoplanets and of young stellar systems is predicting environments and processes that could lead to habitable planets, including development of models that account for the distribution, acquisition, and loss of key volatile elements. Astronomical studies can reveal the architecture of other solar systems (19), the compositions of observable exoplanet atmospheres (ref. 20 and references therein), and the dust and volatile gas structure and composition of protoplanetary disks (ref. 21 and references therein), including interactions of the disk with gas- or ice-giant protoplanets. However, only limited astronomical observations can be made about conversion of disk materials (gas, dust, and pebbles) to planets in other solar systems. To understand this conversion, we must necessarily rely on planetesimals and their remnants (meteorites) as records of the processes that occurred. In this paper, we focus on volatile loss during planetesimal differentiation by examining evidence chiefly from iron meteorites. We note that ephemeral metal enrichments in white dwarf atmospheres confirm that differentiated planetesimals are common around other stars (22), and that our findings apply to how materials would have been processed during the assembly of other planetary systems.In classic oligarchic growth models of planetary origin, planets and embryos grow from accretion of planetesimals with characteristic radii of tens to a few hundreds of kilometers (3). In pebble accretion models of terrestrial planet formation, the fraction of planetesimals in accreting material varies with time and protoplanetary mass (23), but still remains significant. Thus, for understanding volatile delivery to growing planets, an important question is whether the volatile inventory of accreting planetesimals (or larger objects) remained similar to that of primitive materials, typically taken to be comparable to chondritic meteorites, or had diminished significantly from prior differentiation.^*Achondritic meteorites are fragments of differentiated planetesimals and provide direct evidence of processes on small bodies.^† Evidence for volatile loss on silicate achondritic parent bodies comes from elemental concentrations and from isotopes (24–27). However, the best-studied silicate achondritic suites, such as the eucrites and angrites, are igneous crustal rocks (28), and their compositions may not reflect average major volatile contents of their parent bodies. Volatile loss could have been locally enhanced by the igneous activity that produced the planetesimal crusts (29).Iron meteorites offer an additional record of volatile processing in planetesimals. Many, known as “magmatic” irons, originated as metallic cores of planetesimals (30) and potentially record volatile depletions in their parent planetesimals at the time of alloy–silicate separation. Iron meteorites contain measurable amounts both major (S, C, N) and moderately volatile (Ge, Ga) elements and represent the cores of at least 50 parent bodies (31). Thus, known parent body cores are likely survivors from a population of planetesimals that were mostly incorporated into larger bodies and planets. Additionally, isotopic evidence links iron meteorites with both carbonaceous (CC) and noncarbonaceous (NC) chondrites (32), thereby correlating the differentiated planetesimals to their primitive chondritic heritage.Here, we address the problem of planetesimal volatile loss by focusing on carbon and sulfur, two siderophile volatile elements that give important clues to the degassing history of metallic cores recorded iron meteorites and thereby their parent planetesimals.^‡ We begin by examination of C–S systematics in different classes of chondrites. Although chondritic parent bodies formed later than most parent bodies of iron meteorites (33), they provide the best available guide to undifferentiated materials in the early solar system. Their isotopic kinships to iron meteorites (32) suggest that they derive from similar, although not necessarily identical, reservoirs, and so they provide a basis for comparison to those estimated for parent body cores. They also reveal devolatilization processes associated with planetesimal metamorphism. We then examine iron meteorite groups and reconstruct the compositions of their respective parent cores. Finally, we consider a spectrum of simple planetesimal core-formation scenarios and model the resulting C and S distributions. Comparison of these to reconstructed parent core C and S places new constraints on the magnitude of degassing occurring from planetesimal interiors.     

Eosinophil autofluorescence and its use in isolation and analysis of human eosinophils using flow microfluorometry

Unstained human eosinophils exhibit unusually bright autofluorescence, which allows them to be distinguished from other leukocytes using fluorescence microscopy. Eosinophil fluorescence is associated with the cytoplasmic granules of the cells. Eosinophil granule extracts, containing an as-yet-undefined eosinophil fluorescence factor, exhibited excitation maxima at 370 nm and 450 nm, with maximum emission at 520 nm. Eosinophils adhering to opsonized parasites in vitro deposit fluorescent material onto the parasite surface. Eosinophil fluorescence was of sufficient intensity to allow the preparation of viable, highly enriched (greater than or equal to 98%), eosinophil suspensions from peripheral blood of normal and eosinophilic donors using a fluorescence- activated cell sorter. Quantitative studies of eosinophil autofluorescence were performed using flow microfluorometry. Fluorescence intensity of blood eosinophils from normal volunteers and eosinophilic patients varied inversely with the log of the donor's absolute eosinophil count regardless of clinical diagnosis.     

Adriamycin stimulates proliferation of human lymphoblastic leukaemic cells via a mechanism of hydrogen peroxide (H2O2) production

It is becoming clear that adriamycin cytotoxicity may be mediated by semiquinone-free radicals derived from the drug itself and reactive oxygen species (ROS). Recent evidence supports the concept that low concentrations of ROS are able to stimulate cell proliferation, and, based on the observation that subtoxic concentrations of adriamycin can also induce cell proliferation, we hypothesize that low concentrations of adriamycin stimulate cell proliferation by a ROS generation mechanism. We have employed spin-trapping and electron spin resonance (ESR) spectroscopy to investigate the nature of the adriamycin-generated ROS. The spin trap 3,5-dibromo-4-nitrosobenzenesulphonate (DBNBS), which is oxidized in the presence of H₂O₂ and peroxidase enzymes, was used to produce a characteristic three-line spectrum, and it was found that an identical spectrum was produced by human lymphoblastic leukaemic cells (CCRF-CEM cells) after exposure to adriamycin. We tested our hypothesis further by exposing CCRF-CEM cells to subtoxic concentrations of adriamycin (10⁻⁸, 10⁻⁹ and 10⁻¹⁰  M ) and low concentrations of H₂O₂ (10⁻⁸, 10⁻⁹ and 10⁻¹⁰  M ) and subsequently monitored cell proliferation. We found that low concentrations of both adriamycin and H₂O₂ significantly stimulate CCRF-CEM cell proliferation. We therefore conclude that subtoxic concentrations of adriamycin are likely to induce cell proliferation via an H₂O₂ mediated mechanism.     

Somatostatin inhibits insulin and glucagon secretion via two receptors subtypes: an in vitro study of pancreatic islets from somatostatin receptor 2 knockout mice

Somatostatin (SST) potently inhibits insulin and glucagon release from pancreatic islets. Five distinct membrane receptors (SSTR1-5) for SST are known, and at least two (SSTR2 and SSTR5) have been proposed to regulate pancreatic endocrine function. Our current understanding of SST physiology is limited by the receptor subtype selectivity of peptidyl SST analogs, making it difficult to assign a physiological function to an identified SST receptor subtype. To better understand the physiology of SSTRs we studied the in vitro effects of potent subtype-selective nonpeptidyl SST analogs on the regulation of pancreatic glucagon and insulin secretion in wild-type (WT) and in somatostatin receptor 2 knockout (SSTR2KO) mice. There was no difference in basal glucagon and insulin secretion between islets isolated from SSTR2KO and WT mice; however, potassium/arginine-stimulated glucagon secretion was approximately 2-fold higher in islets isolated from SSTR2KO mice. Neither SST nor any SSTR-selective agonist inhibited basal glucagon or insulin release. SST-14 potently inhibited stimulated glucagon secretion in islets from WT mice and much less effectively in islets from SSTR2KO mice. The SSTR2 selective analog L-779,976 inhibited glucagon secretion in islets from WT, but was inactive in islets from SSTR2KO mice. L-817,818, an SSTR5 selective analog, slightly reduced glucagon release in both animal groups, whereas SSTR1, -3, and -4 selective analogs were inactive. SST and L-817,818 inhibited glucose stimulated insulin release in islets from WT and SSTR2KO mice. L-779,976 much less potently reduced insulin secretion from WT islets. In conclusion, our data demonstrate that SST inhibition of glucagon release in mouse islets is primarily mediated via SSTR2, whereas insulin secretion is regulated primarily via SSTR5.     

Thalidomide teratogenesis: evidence for a toxic arene oxide metabolite.

It was postulated that thalidomide causes birth defects by being metabolized to a toxic electrophilic intermediate. This hypothesis was tested by using an in vitro assay in which drug toxicity to human lymphocytes was assessed in the presence of a hepatic microsomal drug metabolizing system. Maternal hepatic microsomes from pregnant rabbits mediated the production of a metabolite that was toxic to lymphocytes. Toxicity was enhanced by inhibitors of epoxide hydrolase (EC 3.3.2.3) and abolished by adding the purified enzyme to the incubation medium. The metabolite thus appears to be in arene oxide, consistent with the previously reported isolation of phenolic metabolites of thalidomide from the urine of treated animals. Two teratogenic analogs of thalidomide (phthalimidophthalimide and phthalimidinoglutarimide) were also toxic in the system; two nonteratogenic analogs (phthalimide and hexahydrothalidomide) were not toxic, even in the presence of epoxide hydrolase inhibitors. The toxic metabolite of thalidomide was not produced by rat liver microsomes (the rat is not sensitive to thalidomide teratogenesis) but was produced by hepatic preparations from maternal rabbits, and rabbit, monkey, and human (all sensitive species) fetuses. A toxic arene oxide therefore may be involved in the teratogenicity of thalidomide.     

Bone marrows of non-Hodgkin's lymphoma patients with a bcl-2 translocation can be purged of polymerase chain reaction-detectable lymphoma cells using monoclonal antibodies and immunomagnetic bead depletion.

Using the extremely sensitive technique of polymerase chain reaction (PCR) to detect the bcl-2 translocation, only 50% of bone marrows could be purged of PCR-detectable lymphoma cells using a cocktail of three anti-B-cell monoclonal antibodies (MoAbs) and complement-mediated lysis. This observation is of clinical importance because those patients whose reinfused marrows harbored residual lymphoma cells showed a significantly increased incidence of relapse. To improve purging, we used PCR detection of the bcl-2 translocation to compare the efficiency of complement-mediated lysis with immunomagnetic bead depletion. Using either a three or a four MoAb cocktail followed by immunomagnetic bead depletion, all PCR-detectable cells were purged after three cycles of treatment. In these same patient samples, treatment with three MoAbs and complement purged only 11 of the 25 (44%) samples. The addition of a fourth MoAb followed by complement lysis purged the marrows of only an additional five patients. Immunomagnetic bead depletion was specific because there was no loss of committed myeloid progenitor cells. The above results suggest that immunomagnetic bead depletion of the harvested marrow will likely be superior to our previous method of purging and the lack of nonspecific toxicity to myeloid progenitor cells predicts that it will not impair engraftment. This methodology will now be used to determine whether the reinfusion of lymphoma free marrow affects the incidence of relapse after autologous bone marrow transplantation.     

Design and Implementation of a Laboratory-Based Drug Design and Synthesis Advanced Pharmacy Practice Experience

Objective. To provide students with an opportunity to participate in medicinal chemistry research within the doctor of pharmacy (PharmD) curriculum.Design. We designed and implemented a 3-course sequence in drug design or drug synthesis for pharmacy students consisting of a 1-month advanced elective followed by two 1-month research advanced pharmacy practice experiences (APPEs). To maximize student involvement, this 3-course sequence was offered to third-year and fourth-year students twice per calendar year.Assessment. Students were evaluated based on their commitment to the project’s success, productivity, and professionalism. Students also evaluated the course sequence using a 14-item course evaluation rubric. Student feedback was overwhelmingly positive. Students found the experience to be a valuable component of their pharmacy curriculum.Conclusion. We successfully designed and implemented a 3-course research sequence that allows PharmD students in the traditional 4-year program to participate in drug design and synthesis research. Students report the sequence enhanced their critical-thinking and problem-solving skills and helped them develop as independent learners. Based on the success achieved with this sequence, efforts are underway to develop research APPEs in other areas of the pharmaceutical sciences.