Perforated colorectal neoplasms: correlation of clinical, contrast enema, and CT examinations

Results of clinical, contrast enema (CE), and computed tomographic (CT) examinations in 39 patients with perforated colorectal neoplasms were retrospectively reviewed. Twenty patients were toxemic at initial presentation, but in only four patients was the diagnosis of perforated colorectal neoplasm initially suspected clinically. CE study was performed in 22 patients and enabled the diagnosis of perforated neoplasm in 11 cases, neoplasm alone in eight, and neither neoplasm nor perforation in three. CT was performed in 38 patients and enabled the diagnosis of perforated neoplasm in 36; pericolic phlegmon but no mass lesion was evident in two. In 16 patients, CT also demonstrated metastatic disease. Because of its reliability in establishing the diagnosis and staging the extent of the inflammatory and neoplastic disease, CT is indicated in cases of suspected or proved perforated colorectal neoplasm and in cases in which CE study findings are indeterminate or suggestive of perforated neoplasm.     

An evaluation of selected oral fluid point-of-collection drug-testing devices

Point-of-collection oral fluids drug-testing devices are being marketed for a variety of medico-legal purposes where they may complement existing technologies and be used to detect drugs following recent ingestion. To assess the utility of these devices for use in drugged-driving investigations, we performed a laboratory evaluation of four devices and those results were published previously. In the study reported here, two more devices, Oratect(R) (Branan) and Uplink(R) (OraSure), were evaluated for their ability to detect amphetamines, cocaine, opiates, and cannabinoids. An additional device, Drugwipe (Securtec), was evaluated for the detection of cocaine and cannabinoids. Each of the devices was assessed for their ability to meet the manufacturers' claimed cutoff concentrations and to meet cutoffs proposed for federal workplace programs. In general, the Branan and OraSure devices detected amphetamine, methamphetamine, opiates, and cannabinoid metabolite (THC-COOH) well in the concentration ranges approximating those proposed by the Substance Abuse and Mental Health Services Administration (SAMHSA), but all three devices performed poorly in detecting Delta9-tetrahydrocannabinol (THC) at the proposed SAMHSA cutoff. The ability to accurately and reliably detect cocaine was dependent on the individual device, and the Branan and Securetec devices were more effective than OraSure at detecting parent cocaine.     

Evaluation of blood parameters by linear discriminant models for the detection of testosterone administration

The steroidal module of the Athlete Biological Passport (ABP) has been used since 2014 for the longitudinal monitoring of urinary testosterone and its metabolites to identify samples suspicious for the use of synthetic forms of Endogenous Anabolic Androgenic Steroids (EAAS). Multiple recent studies have suggested that monitoring of blood parameters may provide enhanced detectability of exogenous testosterone administration. Transdermal and intramuscular testosterone administration studies were carried out in 15 subjects, and the effect on blood steroidal levels, hematological parameters, and gonadotropins was evaluated. Serum testosterone and dihydrotestosterone levels increased while gonadotropin levels were suppressed after administration. A modest increase in reticulocytes was also observed. The blood parameters that were responsive to the administrations were combined into several linear discriminant models targeting both administration (on) and washout (off) phases. The models were effective in detecting the large dose intramuscular administration but were less successful in the detection of the lower dose transdermal application. The blood profiling models may provide complementary value but do not appear to be substantially more advantageous than longitudinal urinary profiling.     

Pharmacology of 5HT(2C) receptor-mediated ERK1/2 phosphorylation: agonist-specific activation pathways and the impact of RNA editing

We have previously characterized a mechanism of 5HT-stimulated extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation via the non-RNA-edited isoform of the serotonin 5HT(2C) receptor (5HT(2C)R-INI) in a CHO cell line. We have now used CV1 cells, which endogenously express epidermal growth factor receptors (EGFRs), to investigate whether the mechanisms underlying ERK1/2 activation by the 5HT(2C)R change in a time-, agonist-, and cell background-dependent manner. Interrogation of the CV1 5HT(2C)R-INI ERK1/2 signaling pathway, using a variety of pathway-selective inhibitors, revealed a clear time-dependence in the involvement of specific pathway components such as phosphatidylinositol 3-kinase, EGFR, matrix metalloproteases and protein kinase C. The contribution of these components to the overall response also varied with the agonist used to stimulate the receptor, providing further evidence for the ability of 5HT(2C)R-INI to signal in an agonist-specific manner. We also investigated the impact of 5HT(2C)R RNA editing on this phenomenon. Although we found no alteration in antagonist pharmacology, the partially edited VSV and fully edited VGV isoforms of the 5HT(2C)R exhibited altered temporal and pharmacological characteristics, including the degree of dependence on specific effectors, in signaling to ERK1/2 in comparison to the 5HT(2C)R-INI. In conclusion, we provide evidence for remarkable flexibility in 5HT(2C)R-mediated ERK1/2 signaling that can be pharmacologically and mechanistically distinct depending on the agonist or edited isoform involved and on the duration of receptor activation.     

Successes in sexual health communications development,programmatic implementation and evaluation in the Torres Strait region 2006 to 2012

Objective: To evaluate the Indigenous sexual health promotion program in the Torres Strait 2006–2012 that culminated in an education‐entertainment radio drama, Kasa Por Yarn (KPY). Methods: A mixed methods approach applied to unpublished program documents and program‐derived peer‐reviewed publications was utilised. Results: Early initiatives established a strong partnership with Torres Strait Islander stakeholders. Significant community engagement throughout ensured a positive process. Telephone survey data (n=100, TSI, 15–24 years) found: 95% had heard of KPY and 80% listened to 2 or more episodes (reach); 86% recalled storylines/characters (recall); and 54% talked about KPY to family/friends (resonance). There was improvement in sexual health knowledge scores (p<0.00) in the 15–19‐year‐old Torres Strait Islander population between 2007 and 2012. The 2012 15–24‐year‐old population exposed to KPY had higher sexual health knowledge scores compared with those unexposed (p=0.02). Conclusions: This is an uncommon comprehensive evaluation of population‐based sexual health communications strategies delivered over years in a remote Australian setting. The findings are encouraging but demonstrate that positive shifts take time and are incremental. Implications: In addition to clinical strategies, strategic and sustained investment in sexual health promotion expertise that leads community partnership and program development is required to reduce youth risk and prevent HIV/AIDS in remote populations.     

A comparison of three vaccines against respiratory syncytial virus in calves

An inactivated vaccine against respiratory syncytial virus (RSV) was compared with two live vaccines. The inactivated (GC) vaccine consisted of glutaraldehyde-fixed bovine nasal mucosa cells persistently infected with RSV and emulsified with oil adjuvant. The live vaccines were a modified virus (MV) derived from a bovine strain of RSV and a temperature-sensitive mutant (ts-1) derived from a human strain. The GC vaccine was inoculated subcutaneously into 12 calves and the live vaccines intramuscularly into eight calves each. Nine unvaccinated calves acted as controls. The vaccines were administered in two doses 3 weeks apart and all calves were challenged intranasally with 2 X 10(7) p.f.u. of bovine RSV 3 weeks after the second dose. At the time of challenge calves given GC, MV and ts-1 vaccines had mean serum neutralizing antibody titres of 25, 19 and 2 respectively; mean titres of IgG1 antibody by radioimmunoassay were log10 4.5, 1.3 and 2.6 respectively and mean zone areas by single radial haemolysis (SRH) were 107, 27 and 36 mm2 respectively. Eleven of 12 calves given GC vaccine were completely protected against challenge but all control animals and those given the two live vaccines were infected. The mean peak titre of virus in nasal swabs of control calves was 3.0 log10 p.f.u./ml and the mean duration of virus shedding was 6.8 days. Both these parameters were significantly reduced in animals given MV and ts-1 vaccines: mean peak titres were 2.1 and 2.4 log10 p.f.u./ml and mean duration of shedding was 3.4 and 3.3 days respectively. Thus, protection correlated better with RSV antibody detected by radioimmunoassay and SRH than with neutralizing antibody. These results are discussed in relation to the possible mechanism by which protection was mediated.     

Expression and distribution of MMPs and TIMPs in human uveal melanoma

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are involved in tumour invasion, metastasis and angiogenesis, and have been implicated as progression markers in uveal melanoma, although their topographical expression has not been fully described. In this study we compared the distribution and specificity of several classes of MMPs (MMP-1, -2, -9, -19, and MT1-MMP) and physiological MMP inhibitors (TIMP-2 and -3) in different regions of the tumour microenvironment and adjacent choroid in a series of primary uveal melanomas. Paraffin sections of untreated uveal melanomas (n=18, 3/18 spindle; 11/18 mixed, and 4/18 epithelioid) were examined for MMP-1 (collagenase 1), MMP-2 and MMP-9 (gelatinases A and B), MT1-MMP (membrane-type 1-MMP), MMP-19, TIMP-2 and TIMP-3 (tissue inhibitors of MMPs), using indirect peroxidase immunohistochemistry. The distribution and intensity of immunolabelling was graded semi-quantitatively (0-3) by 2 independent observers. Non-parametric analyses were used to test for associations between tumour cell type, and the average grade of MMP or TIMP expression. Immunostaining for MMP-1, -9, -19 and MT1-MMP was > or =Grade 2 in more than 70% of specimens, and a heterogeneous pattern of MMP-1, -9, MT1-MMP and TIMP-3 expression was observed. At the tumour-scleral interface (TSI), melanoma cells had a flattened morphology and a much reduced MMP and TIMP expression, with a high expression in tumour areas adjacent to the TSI. Tumour vasculature and stromal cells strongly expressed MMP-2. We also observed heterogeneous immunostaining of the vasculature by MMP-1, -9, MT1-MMP and TIMP-2 antibodies, and of the extravascular matrix by MMP-9 antibody. The distinct immunostaining patterns observed for MMPs and TIMPs within uveal melanoma are consistent with their involvement in tumour growth and angiogenesis. In particular, the heterogeneous expression within regions of the tumours, and the localized expression in vasculature and stromal cells emphasises the importance of the tumour microenvironment in the pathogenesis of uveal melanoma (and other tumours).     

ACHESS ¿ The Australian study of child health in same-sex families: background research, design and methodology

ABSTRACT: BACKGROUND: There are an increasing number of children in Australia growing up with same-sex attracted parents. Although children from same-sex parent families do in general perform well on many psychosocial measures recent research is beginning to consider some small but significant differences when these children are compared with children from other family backgrounds. In particular studies suggest that there is an association between the stigma that same-sex parent families experience and child wellbeing. Research to date lacks a holistic view with the complete physical, mental and social wellbeing of children not yet addressed. In addition, most studies have focused only on families with lesbian parents and have studied only small numbers of children METHODS: The Australian Study of Child Health in Same-Sex Families (ACHESS) is a national study that aims to determine the complete physical, mental and social wellbeing of Australian children under the age 18 years with at least one parent who self identifies as being same-sex attracted. There will be a particular focus on the impact that stigma and discrimination has on these families. Parent and child surveys will be used to collect data and will be available both online and in paper form. Measures have been chosen whenever possible that have sound conceptual underpinnings, robust psychometric properties and Australian normative data, and include the Child Health Questionnaire (CHQ), the Strengths and Difficulties Questionnaire (SDQ) and the Kessler Psychological Distress Scale (K10). DISCUSSION: ACHESS aims to be the largest study of its kind and will for the first time produce a detailed quantitative analysis of Australian children with same-sex attracted parents. By inviting participants to take part in further research it will also establish a valuable cohort of children, and their families, to launch future waves of research that will help us better understand the health and wellbeing of children with same-sex attracted parents.