Adolescent perceptions about participating in HIV-related research studies.

The rising incidence of infection among youth in sub-Saharan Africa makes HIV-related research among younger people a top priority. There remains, however, a lack of consistent and unambiguous ethical principles and guidance for researchers wishing to conduct HIV studies with adolescents. The overarching aim of our research was to better understand youths' experiences with HIV studies. The present study explored four questions: (1) What strategies are effective for recruiting youth for HIV studies? (2) What motivates youth to participate in these studies? (3) How do study participants perceive HIV testing within the context of a research study? (4) What do participants understand about the risks of study participation? These data are essential to inform guidelines for the responsible conduct of research with young people. We interviewed 82 adolescents (aged 15-19) in Kenya taking part in a study examining ethical issues pertaining to their involvement in HIV-related research. Pursuant to our research questions, we found that direct study recruitment combined with encouragement from female relatives was the greatest facilitator to study enrolment among young people. Most young participants expressed that they were motivated to join the study in order to (1) learn their HIV status (n = 49) and (2) receive HIV-related education (n = 26), even though both are already free and widely available. Participants largely preferred testing in a place they deemed "private," although both the health clinic and home were regarded by adolescents as locations with greater privacy. Adolescents largely did not accurately perceive risks of the study two months after baseline, although they could remember the benefits with great clarity. This work can inform researchers, policymakers, and ethics review committees on approaches to maximize efficiency in recruitment and data collection, and to enhance understanding of risks and benefits in HIV-related research among adolescents. While further research is needed, these data may be used by others conducting HIV research in this region to improve recruitment strategies and more effectively engage and appeal to young people.

Bioethics education in Democratic Republic of Congo: Experiences and challenges.

In regions marked by socio-economic turmoil, the task of teaching bioethics to health professionals and researchers can be more challenging than elsewhere. To demonstrate this, in this article we describe some of our teaching experiences in the Democratic Republic of Congo over the past decade. A first difficulty is linguistic. Anglo-Saxon language and culture largely dominates the field of bioethics, complicating teaching and education for those who do not master the language. A second obstacle is conceptual. Bioethics is often misunderstood as reflection on technological developments in medicine, which distorts its objectives and narrows its scope, particularly in resource-constrained settings. A third difficulty is cultural and political. Ethics in this setting is difficult to distinguish from common morality and the work of moralists, who comment on problems in medicine from a religious standpoint. Moreover, when interacting with communities and institutions that are strongly hierarchical, the critical stance of bioethics can give rise to resistance and rejection. These are among the array of difficulties that undoubtedly have given rise to sharp critiques of bioethics training initiatives in developing countries, where the introduction of bioethics has been depicted as a form of Western imperialism. While taking these criticisms seriously, our experiences in the field show how these seemingly insurmountable difficulties can be transformed into (more or less) manageable challenges.

Dans les régions marquées par un contexte socioéconomique difficile, les difficultés sont plus nombreuses qu'ailleurs pour ceux qui se donnent pour tâche de former à la réflexion éthique les professionnels de la santé et les chercheurs. Pour le montrer, nous évoquons dans cet article nos expériences en République Démocratique du Congo. Une première difficulté est à chercher du côté linguistique. En effet, la langue et la culture anglo-saxonnes dominent largement la discipline, compliquant la tâche de ceux qui maîtrisent mal l'anglais. Unedeuxième difficulté à surmonter est d'ordre conceptuel. Les objectifs et le champ d'application de la bioéthique sont souvent mal compris, ce qui peut conduire à confondre les spécialistesde la discipline tantôt avec des moralistes surtout préoccupés par le progrès biotechnologique, tantôt avec des référents religieux. La troisième difficulté évoquée est de nature politique et culturelle. Lorsqu'elle entre en interaction avec des communautés très hiérarchisées et conservatrices, la posture critique de la bioéthique peut susciter des réactions de rejet. Ce sont sans doute ces difficultés qui ont alimenté certaines critiques acerbes sur la pertinence des formations à l'éthique dans des zones marquées par les urgences sanitaires et alimentaires ou certaines accusations présentant ces démarches comme un avatar de plus de l'impérialisme occidental. Tout en prenant au sérieux ces difficultés, nous montrons par nos expériences qu'elles peuvent être transformées en défis à relever.

Glasgow Coma Scale is unreliable for the prediction of severe head injury in elderly trauma patients.

OBJECTIVES AND BACKGROUND: Elderly patients comprise an ever-increasing proportion of major trauma patients. The presenting GCS in elderly patients with traumatic brain injury (TBI) may not reflect the severity of injury as accurately as it does in the younger patient population. However, GCS is often used as part of the decision tool to define the population transferred directly to a major trauma centre. The aim of this study was to explore the relationship between age and presenting GCS in patients with isolated TBI. METHODS: A retrospective database review was undertaken using the Trauma Audit and Research Network database. All patients presenting to Derriford Hospital, Plymouth, between 1 January 2009 and 31 May 2014 with isolated TBI were included. Demographic, mechanistic, physiological, resource use and outcome data were collected. Abbreviated injury scale (AIS) was recorded for all patients. Patients were categorised into those older and younger than 65 years on presentation. Distribution of GCS, categorised into severe (GCS 3-8), moderate (GCS 9-12) and mild TBI (13-15), was compared between the age groups. Median GCS at each AIS level was also compared. RESULTS: The distribution of GCS differed between young and old patients with TBI (22.1% vs 9.8% had a GCS 3-8, respectively) despite a higher burden of anatomical injury in the elderly group. Presenting GCS was higher in the elderly at each level of AIS. The difference was more apparent in the presence of more severe injury (AIS 5). CONCLUSIONS: Elderly patients who have sustained isolated severe TBI may present with a higher GCS than younger patients. Triage tools using GCS may need to be modified and validated for use in elderly patients with TBI.

Could human challenge studies for COVID-19 vaccines be justified in South Africa?

Although human challenge studies (HCSs) have been widely employed in vaccine development for malaria, dengue, typhoid and cholera, the role of this research design in COVID-19 remains controversial. While the potential social value of HCSs in the context of a pandemic is clear, bioethicists are divided on the ethics, given that effective treatment for COVID-19 has eluded us to date. While compelling ethics arguments have been offered on both sides of the debate, scientific and regulatory complexities may not have been fully appreciated. Furthermore, accelerated development of efficacious vaccine candidates in traditional clinical trials has diluted some of the arguments in favour of HCSs. In low- and middle-income country settings, including South Africa, the need for robust patient care conditions for the conduct of HCSs, coupled with considerations such as perceptions of risk, consent processes, remuneration, vaccine hesitancy, fear of exploitation and access to vaccines, makes HCSs challenging to justify.

Comparative strategic approaches to COVID-19 in Africa: Balancing public interest with civil liberties.

As COVID-19 spreads rapidly across Africa, causing havoc to economies and disruption to already fragile healthcare systems, it is becoming clear that despite standardised global health strategies, national and local government responses must be tailored to their individual settings. Some African countries have adopted stringent measures such as national lockdown, quarantine or isolation, in combination with good hand hygiene, mandatory wearing of masks and physical distancing, to prevent an impending healthcare crisis. The impact of stringent measures in low- to middle-income African countries has bought time for healthcare facilities to prepare for the onslaught of COVID-19 cases, but some measures have been challenging to implement. In some settings, public health measures have been associated with serious violations of individual rights owing to abuse of power and gaps in implementation of well-intentioned policy. Collateral damage with regard to non-COVID-19 diseases that were suboptimally managed in pre-pandemic times may mean that lives lost from other diseases could exceed those saved from COVID-19. While individuals complying with lockdown regulations have embraced an acceptance of the concept of the common good, at a broad community level many are finding the transition from individualism to collective thinking required during a pandemic difficult to navigate. In this article, we look at government responses to the pandemic in six African countries (Malawi, South Africa, Uganda, Zambia, Zimbabwe and Botswana), and highlight ethical concerns arising in these contexts.

Topo IIIalpha and BLM act within the Fanconi anemia pathway in response to DNA-crosslinking agents.

The Bloom protein (BLM) and Topoisomerase IIIalpha are found in association with proteins of the Fanconi anemia (FA) pathway, a disorder manifesting increased cellular sensitivity to DNA crosslinking agents. In order to determine if the association reflects a functional interaction for the maintenance of genome stability, we have analyzed the effects of siRNA-mediated depletion of the proteins in human cells. Depletion of Topoisomerase IIIalpha or BLM leads to increased radial formation, as is seen in FA. BLM and Topoisomerase IIIalpha are epistatic to the FA pathway for suppression of radial formation in response to DNA interstrand crosslinks since depletion of either of them in FA cells does not increase radial formation. Depletion of Topoisomerase IIIalpha or BLM also causes an increase in sister chromatid exchanges, as is seen in Bloom syndrome cells. Human Fanconi anemia cells, however, do not demonstrate increased sister chromatid exchanges, separating this response from radial formation. Primary cell lines from mice defective in both Blm and Fancd2 have the same interstrand crosslink-induced genome instability as cells from mice deficient in the Fancd2 protein alone. These observations demonstrate that the association of BLM and Topoisomerase IIIalpha with Fanconi proteins is a functional one, delineating a BLM-Topoisomerase IIIalpha-Fanconi pathway that is critical for suppression of chromosome radial formation.

Identification of decomposition volatile organic compounds from surface-deposited and submerged porcine remains.

Cadaver dogs are routinely used internationally by police and civilian search organisations to locate human remains on land and in water, yet little is currently known about the volatile organic compounds (VOCs) that are released by a cadaver underwater; how this compares to those given off by a cadaver deposited on land; and ultimately, how this affects the detection of drowned victims by dogs. The aim of this study was to identify the VOCs released by whole porcine (Sus scrofa domesticus) cadavers deposited on the surface and submerged in water using solid phase microextraction gas chromatography mass spectrometry (SPME GC-MS) to ascertain if there are notable differences in decomposition odour depending on the deposition location. For the first time in the UK, the volatile organic compounds (VOCs) from the headspace of decomposing porcine cadavers deposited in both terrestrial and water environments have been detected and identified using SPME-GCMS, including thirteen new VOCs not previously detected from porcine cadavers. Distinct differences were found between the VOCs emitted by porcine cadavers in terrestrial and water environments. In total, seventy-four VOCs were identified from a variety of different chemical classes; carboxylic acids, alcohols, aromatics, aldehydes, ketones, hydrocarbons, esters, ethers, nitrogen compounds and sulphur compounds. Only forty-one VOCs were detected in the headspace of the submerged pigs with seventy detected in the headspace of the surface-deposited pigs. These deposition-dependent differences have important implications for the training of cadaver dogs in the UK. If dog training does not account for these depositional differences, there is potential for human remains to be missed. Whilst the specific odours that elicit a trained response from cadaver dogs remain unknown, this research means that recommendations can be made for the training of cadaver dogs to incorporate different depositions, to account for odour differences and mitigate the possibility of missed human remains operationally.

The process of HIV status disclosure to HIV-positive youth in Kinshasa, Democratic Republic of the Congo.

As access to HIV/AIDS treatment increases in sub-Saharan Africa, greater attention is being paid to HIV-infected youth. Little is known about how HIV-positive youth are informed of their HIV infection. As part of a larger formative study informing a treatment program in Kinshasa, Democratic Republic of the Congo, semi-structured interviews were conducted with 19 youth (10-21 years) who had previously been told their HIV status and 21 caregivers who had disclosed the youth's HIV status to the youth. Questions explored youth's and caregivers' experiences of and immediate reactions to disclosure. Youth's median age at disclosure was 15 years old, with a range of 10-18 years based on caregiver reports (n=21) and from 10-19 years based on youth reports (n=18). The most common reasons spontaneously given for disclosing were the child's adherence to their treatment regimen (5/16), the need of the child to protect her/himself or stay healthy (5/16), the child's increasing age (4/16) and so that the child would know why they are suffering (3/16). Most youth (16/19) were surprised to learn of their diagnosis; 50% (8/16) wondered about the infection's origins. A large majority felt that it is better for them to know their HIV status (88%; 15/17). HIV care and treatment programs must be prepared to address the psychosocial needs of youth and their caregivers during the disclosure process.

An Investigation on the Persistence of Uranium Hydride during Storage of Simulant Nuclear Waste Packages.

Synchrotron X-rays have been used to study the oxidation of uranium and uranium hydride when encapsulated in grout and stored in de-ionised water for 10 months. Periodic synchrotron X-ray tomography and X-ray powder diffraction have allowed measurement and identification of the arising corrosion products and the rates of corrosion. The oxidation rates of the uranium metal and uranium hydride were slower than empirically derived rates previously reported for each reactant in an anoxic water system, but without encapsulation in grout. This was attributed to the grout acting as a physical barrier limiting the access of oxidising species to the uranium surface. Uranium hydride was observed to persist throughout the 10 month storage period and industrial consequences of this observed persistence are discussed.

Cell proliferation and enzyme activities associated with the development of avian tibial dyschondroplasia: an in situ biochemical study.

Avian tibial dyschondroplasia is a disorder of endochondral ossification which results in the accumulation of noncalcified, avascular cartilage. We have investigated the changes in cell proliferation and enzyme activities within specific cell types in the growth plate of chickens with differing severity of the disease using in situ biochemical techniques that allow the quantification of enzyme activity in unfixed undecalcified sections of tissue. Lactate dehydrogenase activity in the prehypertrophic zone and tartrate-resistant acid phosphatase activity in osteoclasts/chondroclasts were not affected by the severity of the disease. Glucose 6-phosphate dehydrogenase activity in both the proliferating and prehypertrophic zones of the growth plate was reduced in chicks with both moderate and severe lesions. Cell proliferation within the proliferating chondrocytes was slightly reduced in the severely affected birds. Alkaline phosphatase activity in the prehypertrophic chondrocytes was markedly elevated in chicks with moderate and severe lesions. These results rule out an increased rate of chondrocyte proliferation as a possible mechanism for the development of tibial dyschondroplasia. The aetiology of the disease therefore appears to be related to the control of chondrocyte differentiation, mineralization, and vascularization by local and/or systemic growth factors.

Growth-promoting interactions between the murine neocortex and thalamus in organotypic co-cultures.

The aim of this study was to assess whether developing cerebral cortex produces diffusible factors that can affect the growth of thalamic cells and, if so, what the role of these factors might be during the formation of thalamocortical connections. We studied interactions between cultured organotypic explants from mice maintained in defined serum-free medium. First, we cultured explants of embryonic dorsolateral thalamus in isolation from any other tissue; after culture, these explants were viewed intact and then sectioned. We estimated the numbers of healthy and pyknotic cells before and after culture, and the rates of mitosis in the explants during culture (using bromodeoxyuridine). Based on these data, we concluded that the majority of cells in the thalamic explants survived, although significant numbers of pyknotic cells did accumulate. Thalamic explants extended either very few or no neurites when cultured alone. We then cultured explants of embryonic thalamus near to explants from other tissues. A gap was always maintained between the explants, and we measured the length and density of neurite outgrowth from each thalamic explant. Slices of embryonic cortex promoted a small but significant increase in the amount of growth from thalamic explants. Postnatal cortex stimulated much more profuse neurite outgrowth; postnatal cerebellum had less of an effect, and postnatal medulla or liver had none. We showed that there was significantly more outgrowth from thalamic explants cultured in medium that had been preconditioned with cortical slices than from thalamic explants cultured in control medium, confirming that diffusible factors were produced by the cortex. The survival and mitotic rates of thalamic cells were unaffected by co-culture with the cortex. We conclude that the developing cortex releases diffusible factors that stimulate the growth of thalamic neurites and that other regions of the brain may also release the same substance(s). The lack of a specific source of thalamic growth promoting factor(s) argues against a role for these factors in guiding thalamic axons to specific targets; indeed, we were unable to demonstrate any chemotropic guidance of thalamic axons towards cortical explants in collagen gels. Since postnatal cortex has a more potent stimulatory effect than prenatal cortex, it seems possible that, in vivo, the cortical-derived factors act mainly on thalamocortical axons that have located their targets and are in the process of arborizing and refining their connections.

Fungal surveillance of an open haematology ward.

Air sampling and surveillance cultures for fungi were performed in a Scottish general haematology ward over a five-month period in 1997. The mean total fungal count from the air sampling appeared to be correlated with the number of patients colonized by Aspergillus. The most commonly isolated species were Aspergillus versicolor, A. fumigatus and A. niger. Rooms with portable air filtration units had significantly lower total fungal counts than the others. Swabs were taken from 70 patients (mean age 62 years); 114 of the 563 cultures (20.2%) were positive. The most commonly isolated species were A. fumigatus, Candida albicans, C. glabrata and C. parapsilosis. Samples taken from the tongue and perineum showed colonization more often than those taken from the nostrils. Almost half the patients (48.6%) were colonized on, or within seven days of, admission; 11.4% became colonized whilst on the unit. One patient developed fatal aspergillosis. We conclude that colonization or high air-borne spore concentrations are not necessarily predictive of fungal infection but may prompt early treatment or more aggressive prophylaxis of potentially fatal invasive infections.

Production of digoxigenin-labelled RNA probes and the detection of cytokine mRNA in rat spleen and brain by in situ hybridization.

Non-radioactive in situ hybridization is a sensitive method for determining the site of production for secretory molecules such as cytokines. We report here on the central and peripheral induction of proinflammatory cytokines by endotoxin, and outline procedures for the generation and application of rat-specific digoxigenin (Dig)-labelled RNA probes for the localization of mRNA by in situ hybridization. Rats were injected either intravenously (i.v.) or intracerebroventricularly (i.c.v.) with vehicle or lipopolysaccharide (LPS) and sacrificed at various time intervals post-injection. Rats were then perfused with 4% paraformaldehyde and the spleens and brains were removed and cryoprotected in 30% sucrose. Dig-labelled, rat-specific, antisense and sense RNA probes were generated by in vitro transcription from PCR-derived templates. Positive staining with all the antisense probes was cytoplasmic, whereas the sense probes showed no staining. Numerous tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) mRNA positive cells were observed in the marginal zone and in the red pulp of the spleen after iv LPS injections, whereas sections from saline-treated animals showed minimal cytokine mRNA expression. Cells positive for TNF-alpha and IL-1beta mRNA were detectable in the brain after i.c.v. injections of LPS, but not after icv injection of vehicle. An antisense probe for c-fos was utilized in these studies as a positive control for our procedure due to its anatomically specific expression in the rat brain after LPS. In conclusion we have demonstrated that in situ hybridization with Dig-labelled RNA probes is an efficient, sensitive and reliable tool to localize cytokine mRNA production in rat tissue.

Immunohistochemical evaluation of vasopressin expression in breast fibrocystic disease and ductal carcinoma in situ (DCIS).

We previously found that expression of the vasopressin gene is a common feature of human breast cancer. In the present study we first examined 21 different cases of benign fibrocystic breast disease for vasopressin expression using immunohistochemistry and antibodies directed against vasopressin (anti-VP) and against vasopressin-associated glycopeptide (anti-VAG). All cases examined were negative for vasopressin gene expression using these antibodies. Alternatively, we examined 16 cases of breast ductal carcinoma in situ (DCIS) using the second of these antibodies (anti-VAG), and all of these cases were positive for vasopressin gene expression. Our results suggest that products of vasopressin gene expression are not markers of cellular proliferation in the breast, and might rather represent an early part of the carcinogenic process in this tissue.

Fluid replacement needs of well-trained male and female athletes during indoor and outdoor steady state running.

Twelve male and six female well-trained middle distance athletes performed a series of six one hour runs at 75% VO2 peak pace under similar environmental states indoors (treadmill) and outdoors (track). Running was undertaken in control (C, no fluid), followed by water (W) and sports drink (SD) treatments, with each run separated by a one week interval. Both fluid treatments were supplied in volumes equivalent to individual body mass (fluid) losses incurred in the respective indoor and outdoor C treatments. Haemodynamic (plasma volume), physiological (heart rate and body temperature) and blood chemistry (blood lactate and glucose) measures were analysed as pre to post run changes (delta values). During the respective indoor and outdoor C treatments, males demonstrated approximately a twofold change in body mass (fluid) losses (delta 1.81 +/- 0.10 kg and 2.06 +/- 0.13 kg) compared with females (delta 0.93 +/- 0.11 kg and 1.32 +/- 0.12 kg) (all p<0.05). These losses resulted in almost a twofold fluid replacement need relative to body mass during the running phases of respective indoor and outdoor W and SD treatments in males compared with females (all p<0.05). Both W and SD treatments were effective in minimising the pre to post run disturbances in plasma volume, heart rate, body temperature and blood lactate, while SD treatment resulted in enhanced blood glucose changes. The results suggest gender specific differences in fluid replacement needs during steady state running, which need to be incorporated into fluid replacement strategies to compensate for the demands of training and competition in middle distance athletic events.

Differences in medical students' attitudes to academic misconduct and reported behaviour across the years--a questionnaire study.

OBJECTIVES: This study aimed to determine attitudinal and self reported behavioural variations between medical students in different years to scenarios involving academic misconduct. DESIGN: A cross-sectional study where students were given an anonymous questionnaire that asked about their attitudes to 14 scenarios describing a fictitious student engaging in acts of academic misconduct and asked them to report their own potential behaviour. SETTING: Dundee Medical School. PARTICIPANTS: Undergraduate medical students from all five years of the course. METHOD: Questionnaire survey. MAIN MEASUREMENTS: Differences in medical students' attitudes to the 14 scenarios and their reported potential behaviour with regards to the scenarios in each of the years. RESULTS: For most of the scenarios there was no significant difference in the response between the years. Significant differences in the responses were found for some of the scenarios across the years, where a larger proportion of year one students regarded the scenario as wrong and would not engage in the behaviour, compared to other years. These scenarios included forging signatures, resubmitting work already completed for another part of the course, and falsifying patient information. CONCLUSION: Observed differences between the years for some scenarios may reflect a change in students' attitudes and behaviour as they progress though the course. The results may be influenced by the educational experience of the students, both in terms of the learning environment and assessment methods used. These differences may draw attention to the potential but unintentional pressures placed on medical students to engage in academic misconduct. The importance of developing strategies to engender appropriate attitudes and behaviours at the undergraduate level must be recognised.

The determination of the relevance of basic sciences learning objectives to clinical practice using a questionnaire survey.

OBJECTIVES: Facilitating sufficient understanding of the basic sciences to underpin clinical practice is important in producing the good doctor. However, the inclusion of irrelevant material in the curriculum not only wastes valuable learning time, but may also hinder learning. The aim of this study was to determine how relevant staff and students thought respiratory basic science learning objectives were to medical practice. DESIGN: The study involved a survey using an anonymous questionnaire to determine whether the respiratory learning objectives stated in Year 1 were perceived as relevant to clinical practice. Each learning objective was rated as being 'relevant', 'not relevant' or of 'uncertain relevance'. SETTING: Dundee Medical School, UK. SUBJECTS: Junior and senior students and staff. RESULTS: Year 1 students considered the majority of the learning objectives to be relevant to clinical practice. Staff and senior students identified some respiratory learning objectives as not relevant to clinical practice, most of which were related to biochemistry. CONCLUSIONS: The identification of learning objectives with questionable relevance to clinical practice requires careful consideration to determine whether these should be removed from the course. Attention needs to be given to both the presentation and process by which material is delivered to students. Strategies to emphasise the clinical relevance of the basic sciences to students are discussed. Further research needs to be conducted to evaluate what knowledge is essential for producing good doctors.

A switch in the direction of the effect of insulin on the partitioning of hepatic fatty acids for the formation of secreted triacylglycerol occurs in vivo, as predicted from studies with perfused livers.

The direct effects of insulin on hepatic triacylglycerol secretion are important because they may determine the degree of postprandial hyperlipidaemia, a known risk factor for the development of atherosclerotic lesions. Previous work from this laboratory, conducted on isolated perfused rat livers [Zammit, V.A., Lankester, D.J., Brown, A.M. & Park, B.S. (1999) Eur. J. Biochem. 263, 859-864], has indicated that the effect of insulin on hepatic triacylglycerol secretion is dependent on the prior physiological state of the donor animals. In this paper, we demonstrate that a switch in the direction of insulin action on hepatic partitioning of fatty acyl moieties towards triacylglycerol secretion also occurs in vivo between the fed, normoinsulinaemic state and the fasted or severely insulin-deficient states. The partitioning of fatty acids in the liver of awake, unstressed rats was studied using selective labelling of hepatic fatty acids during hyperinsulinaemic-euglycaemic clamps achieved through the use of hepatocyte-targeted liposome-encapsulated insulin preparations. The data show that, whereas in the fed, normoinsulinaemic state, insulinization of the liver raises the proportion of fatty acids directed towards secreted triacylglycerol, in the fasted or insulin-deficient states, insulin inhibits the partitioning of acyl moieties into secreted triacylglycerol. These data show that observations on the direction of insulin action on hepatic triacylglycerol secretion obtained using isolated perfused rat livers are reflected in the effects of the hormone on hepatic fatty acid partitioning in vivo. They offer an explanation for the positive relationship between chronic hyperinsulinaemia, hepatic VLDL-triacylglycerol secretion and hypertriglyceridaemia observed previously in insulin-resistant states.