Consequences,conditions and caveats: a qualitative exploration of the influence of undergraduate health professions students at distributed clinical training sites

Background

Traditionally, the clinical training of health professionals has been located in central academic hospitals. This is changing. As academic institutions explore ways to produce a health workforce that meets the needs of both the health system and the communities it serves, the placement of students in these communities is becoming increasingly common. While there is a growing literature on the student experience at such distributed sites, we know less about how the presence of students influences the site itself. We therefore set out to elicit insights from key role-players at a number of distributed health service-based training sites about the contribution that students make and the influence their presence has on that site.

Methods

This interpretivist study analysed qualitative data generated during twenty-four semi-structured interviews with facility managers, clinical supervisors and other clinicians working at eight distributed sites. A sampling grid was used to select sites that proportionally represented location, level of care and mix of health professions students. Transcribed data were subjected to thematic analysis. Following an iterative process, initial analyses and code lists were discussed and compared between team members after which the data were coded systematically across the entire data set.

Results

The clustering and categorising of codes led to the generation of three over-arching themes: influence on the facility (culturally and materially); on patient care and community (contribution to service; improved patient outcomes); and on supervisors (enriched work experience, attitude towards teaching role). A subsequent stratified analysis of emergent events identified some consequences of taking clinical training to distributed sites. These consequences occurred when certain conditions were present. Further critical reflection pointed to a set of caveats that modulated the nature of these conditions, emphasising the complexity inherent in this context.

Conclusions

The move towards training health professions students at distributed sites potentially offers many affordances for the facilities where the training takes places, for those responsible for student supervision, and for the patients and communities that these facilities serve. In establishing and maintaining relationships with the facilities, academic institutions will need to be mindful of the conditions and caveats that can influence these affordances.

     

Serum-induced enhancement of peripheral blood mononuclear cell mediated cytotoxicity towards human target cells in systemic lupus erythematosus

Sera from 6 out of 18 patients with systemic lupus erythematosus (SLE) were found to be capable of producing marked increases of cytotoxicity in several established human target cell lines when co-cultured with normal human peripheral blood mononuclear cells (PBM). Fractionation studies indicated that the cytotoxicity-inducing activity resided in IgG containing fractions and that the effector cells were Fc-receptor positive. By contrast, sera from 27 normal controls produced little or no cytotoxicity when similarly co-cultured with the same target cell lines and normal PBM. Any slight reactivity that occasionally occurred against a single cell line was, on serum fractionation, either labile or associated with albumen containing fractions. These findings raise the possibility that antibody-dependent cellular cytotoxicity could provide an additional pathogenetic mechanism in patients with SLE.     

Keratin 19 marks poor differentiation and a more aggressive behaviour in canine and human hepatocellular tumours

Background  

The expression of Keratin 19 (K19) was reported in a subset of hepatocellular carcinomas (HCCs). K19 positive HCCs are associated with an increased malignancy compared to K19 negative HCCs. No suitable mouse models exist for this subtype of HCC, nor is the incidence of K19 expression in hepatocellular neoplasia in model animals known. Therefore, we compared the occurrence and tumour behaviour of K19 positive hepatocellular neoplasias in dog and man.     

Quantitation of benzo[a]pyrene metabolic profiles in human bronchoalveolar (H358) cells by stable isotope dilution liquid chromatography-atmospheric pressure chemical ionization mass spectrometry

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants and are carcinogenic in multiple organs and species. Benzo[a]pyrene (B[a]P) is a representative PAH and has been studied extensively for its carcinogenicity and toxicity. B[a]P itself is chemically inert and requires metabolic activation to exhibit its toxicity and carcinogenicity. Three major metabolic pathways have been well documented. The signature metabolites generated from the radical cation (peroxidase or monooxygenase mediated) pathway are B[a]P-1,6-dione and B[a]P-3,6-dione, the signature metabolite generated from the diol-epoxide (P450 mediated) pathway is B[a]P-r-7,t-8,t-9,c-10-tetrahydrotetrol (B[a]P-tetrol-1), and the signature metabolite generated from the o-quinone (aldo-keto reductase mediated) pathway is B[a]P-7,8-dione. The contributions of these different metabolic pathways to cancer initiation and the exploitation of this information for cancer prevention are still under debate. With the availability of a library of [(13)C(4)]-labeled B[a]P metabolite internal standards, we developed a sensitive stable isotope dilution atmospheric pressure chemical ionization tandem mass spectrometry method to address this issue by quantitating B[a]P metabolites from each metabolic pathway in human lung cells. This analytical method represents a 500-fold increased sensitivity compared with that of a method using HPLC-radiometric detection. The limit of quantitation (LOQ) was determined to be 6 fmol on column for 3-hydroxybenzo[a]pyrene (3-OH-B[a]P), the generally accepted biomarker for B[a]P exposure. This high level of sensitivity and robustness of the method was demonstrated in a study of B[a]P metabolic profiles in human bronchoalveolar H358 cells induced or uninduced with the AhR ligand, 2,3,7,8-tetrachlorodibenzodioxin (TCDD). All the signature metabolites were detected and successfully quantitated. Our results suggest that all three metabolic pathways contribute equally in the overall metabolism of B[a]P in H358 cells with or without TCDD induction. The sensitivity of the method should permit the identification of cell-type differences in B[a]P activation and detoxication and could also be used for biomonitoring human exposure to PAH.     

Metabolism and distribution of benzo[a]pyrene-7,8-dione (B[a]P-7,8-dione) in human lung cells by liquid chromatography tandem mass spectrometry: detection of an adenine B[a]P-7,8-dione adduct

Benzo[a]pyrene-7,8-dione (B[a]P-7,8-dione) is produced in human lung cells by the oxidation of (±)-B[a]P-7,8-trans-dihydrodiol, which is catalyzed by aldo-keto reductases (AKRs). However, information relevant to the cell-based metabolism of B[a]P-7,8-dione is lacking. We studied the metabolic fate of 2 μM 1,3-[(3)H(2)]-B[a]P-7,8-dione in human lung adenocarcinoma A549 cells, human bronchoalveolar H358 cells, and immortalized human bronchial epithelial HBEC-KT cells. In these three cell lines, 1,3-[(3)H(2)]-B[a]P-7,8-dione was rapidly consumed, and radioactivity was distributed between the organic and aqueous phase of ethyl acetate-extracted media, as well as in the cell lysate pellets. After acidification of the media, several metabolites of 1,3-[(3)H(2)]-B[a]P-7,8-dione were detected in the organic phase of the media by high performance liquid chromatography-ultraviolet-radioactivity monitoring (HPLC-UV-RAM). The structures of B[a]P-7,8-dione metabolites varied in the cell lines and were identified as B[a]P-7,8-dione conjugates with glutathione (GSH) and N-acetyl-l-cysteine (NAC), 8-O-monomethylated-catechol, catechol monosulfate, and monoglucuronide, and monohydroxylated-B[a]P-7,8-dione by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We also obtained evidence for the first time for the formation of an adenine adduct of B[a]P-7,8-dione. Among these metabolites, the identity of the GSH-B[a]P-7,8-dione and the NAC-B[a]P-7,8-dione was further validated by comparison to authentic synthesized standards. The pathways of B[a]P-7,8-dione metabolism in the three human lung cell lines are formation of GSH and NAC conjugates, reduction to the catechol followed by phase II conjugation reactions leading to its detoxification, monohydroxylation, as well as formation of the adenine adduct.     

Multidrug resistance protein (MRP) 4 attenuates benzo[a]pyrene-mediated DNA-adduct formation in human bronchoalveolar H358 cells

Multi-drug resistance protein (MRP) 4, an ATP-binding cassette (ABC) transporter, has broad substrate specificity. It facilitates the transport of bile salt conjugates, conjugated steroids, nucleoside analogs, eicosanoids, and cardiovascular drugs. Recent studies in liver carcinoma cells and hepatocytes showed that MRP4 expression is regulated by the aryl hydrocarbon receptor (AhR) and nuclear factor E2-related factor 2 (Nrf2). The AhR has particular importance in the lung and is most commonly associated with the up-regulation of cytochrome P-450 (CYP)-mediated metabolism of benzo[a]pyrene (B[a]P) to reactive intermediates. Treatment of H358, human bronchoalveolar, cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or (−)-benzo[a]pyrene-7,8-dihydro-7,8-diol (B[a]P-7,8-dihydrodiol), the proximate carcinogen of B[a]P, revealed that MRP4 expression was increased compared to control. This suggested that MRP4 expression might contribute to the paradoxical decrease in (+)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-2′-deoxyguanosine ((+)-anti-trans-B[a]PDE-dGuo) DNA-adducts observed in TCDD-treated H358 cells. We have now found that decreased MRP4 expression induced by a short hairpin RNA (shRNA), or chemical inhibition with probenecid, increased (+)-anti-trans-B[a]PDE-dGuo formation in cells treated with (−)-B[a]P-7,8-dihydrodiol, but not the ultimate carcinogen (+)-anti-trans-B[a]PDE. Thus, up-regulation of MRP4 increased cellular efflux of (−)-B[a]P-7,8-dihydrodiol, which attenuated DNA-adduct formation. This is the first report identifying a specific MRP efflux transporter that decreases DNA damage arising from an environmental carcinogen.     

In vitro differentiation of liver progenitor cells derived from healthy dog livers

Naturally occurring liver disease in dogs resemble human liver disease in great detail; including the activation of liver progenitor cells (LPC) in acute and chronic liver disease. The aim of the present study was to isolate, culture, and characterize progenitor cells derived from healthy mature dog livers. A nonparenchymal cell fraction enriched with small hepatocytes was isolated and cultured in Hepatozyme-serum-free media (SFM) to stimulate the growth of colony-forming small epithelial cells. After 2 weeks of culturing, clonal expansion of keratin 7 (K7) immunopositive small cells with a large nucleus/cytoplasm ratio emerged in the hepatocyte monolayer. These colonies expressed genes of several hepatocyte (CYP1A1, ALB, and KRT18), cholangiocyte/LPC (KRT7 and KRT19), and progenitor cell markers (alpha-fetoprotein, CD44, prominin1, KIT, THY1, and neural cell adhesion molecule 1), indicating their immature and bipotential nature. Gene-expression profiles indicated a more pronounced hepatic differentiation in Hepatozyme-SFM compared to William's Medium E (WME). Furthermore, colony-forming cells differentiated toward intermediate hepatocyte-like cells with a more pronounced membranous K7 immunostaining. In conclusion, colony-forming small epithelial cells in long-term canine liver cell cultures express LPC markers and have differentiating capacities. These cells may therefore be considered as progenitor cells of the liver.     

Unnoticed post-void residual urine volume in people with moderate to severe intellectual disabilities: prevalence and risk factors

Background   Increased post-void residual urine volume (PVR) is often seen in geriatric populations. People with intellectual disabilities (ID) have risk factors in common with these populations.
Aims   To investigate in adults with ID:

• • 

  Feasibility of portable ultrasound bladder scanning;
• • 

  Prevalence of PVR; and
• • 

  Relations with proposed risk factors for PVR.

Methods   In a cross-sectional design, PVR was measured using ultrasound scanning in 346 adults with moderate to severe ID aged 18–82 years. Relationship between increased PVR and the following risk factors was assessed: age, level of ID, gender, ambulancy, medication, chronic illnesses, incontinence and profound multiple disabilities (PMD). Acceptation of scanning and manageability were noted.
Results   Feasibility: All participants were cooperatively undergoing the ultrasound scan and all outcomes were sufficiently interpretable. Prevalence: PVR ≥ 150 mL was newly identified in 30/346 persons (8.7%, 95% confidence interval 5.92–12.14). Associations: Higher age ( P  = 0.001), laxative use ( P  = 0.001), chronic illnesses other than epilepsy ( P  = 0.005), profound ID ( P  = 0.008), incontinence ( P  = 0.048) and immobility ( P  = 0.005) are determinants that were associated with urinary retention.
Conclusions   The bladder ultrasound scan is a feasible method to identify increased PVR in adults with more severe levels of ID. The prevalence of PVR in adults is similar to prevalences found in the geriatric general population.     

Imaging characteristics following 90yttrium microsphere treatment for unresectable liver cancer

Selective internal radiation therapy (SIRT) with (90)yttrium microspheres - also known as radioembolisation - is a relatively new interventional radiology technique offering symptomatic and survival advantages for patients with unresectable liver cancer. However, in delivering both beta-particle brachytherapy and embolisation of tumour vasculature, SIRT produces biological sequelae and imaging characteristics distinct from other treatment modalities. Current CT interpretation criteria consistently under-report pathological responses to radioembolisation, diminishing both the prognosis and subsequent treatment choices for responding patients. However, newer criteria incorporating both tumour dimensions and enhancement characteristics improve the correlation with histopathology and provide substantially earlier confirmation of response. CT following radioembolisation may also identify parenchymal features that are often benign but may be mistaken for tumour progression. This review outlines imaging criteria specific to SIRT, including assessment of tumour response and interpretation of both lesion and parenchymal characteristics. The adjunctive role of additional modalities such as positron emission tomography is also addressed.