The effect of infusions of adrenaline, noradrenaline and dopamine on cerebral autoregulation under isoflurane anaesthesia in an ovine model

Publisher's copy made available with the permission of the publisher © Australian Society of AnaesthetistsThe effects of infusions of adrenaline, noradrenaline and dopamine on cerebral autoregulation under steady-state isoflurane anaesthesia were compared with the awake state. Six studies each were conducted in two cohorts of adult ewes: awake sheep and those anaesthetized with 2% isoflurane anaesthesia. In random order, each animal received ramped infusions of adrenaline, noradrenaline (0-40 µg/min) and dopamine (0-40 µg/kg/min). Cerebral blood flow was measured continuously from changes in Doppler velocities in the sagittal sinus. Autoregulation was determined by linear regression analysis between cerebral blood flow and mean arterial pressure. Isoflurane did not significantly alter cerebral blood flow relative to pre-anaesthesia values (P>0.05). All three catecholamines significantly and equivalently increased MAP from baseline in a dose dependent manner in both the awake and isoflurane cohorts. Although adrenaline significantly increased cerebral blood flow from baseline in the awake cohort (P0.05). Over a specific dose range, systemic hypertension induced by adrenaline, noradrenaline and dopamine did not significantly increase cerebral blood flow under 2% isoflurane anaesthesia. The concomitant administration of isoflurane and the catecholamines was not associated with altered autoregulatory function compared to the awake state.http://www.aaic.net.au/Article.asp?D=200236

Cerebrovascular carbon dioxide reactivity in sheep: Effect of propofol or isoflurane anaesthesia

Publisher's copy made available with the permission of the publisher © Australian Society of AnaesthetistsPropofol and isoflurane are commonly used in neuroanaesthesia. Some published data suggest that the use of these agents is associated with impaired cerebral blood flow/carbon dioxide (CO₂) reactivity. Cerebrovascular CO₂ reactivity was therefore measured in three cohorts of adult merino sheep: awake (n=6), anaesthetized with steady-state propofol (15 mg/min; n=6) and anaesthetized with 2% isoflurane (n=6). Changes in cerebral blood flow were measured continuously from changes in velocities of blood in the sagittal sinus via a Doppler probe. Alterations in the partial pressure of carbon dioxide in arterial blood (PaCO₂) over the range 18-63 mmHg were achieved by altering either the inspired CO₂ concentration or the rate of mechanical ventilation. Cerebral blood flow/CO₂ relationships were determined by linear regression analysis, with changes in cerebral blood flow expressed as a percentage of the value for a PaCO₂ of 35 mmHg. Propofol decreased cerebral blood flow by 55% relative to pre-anaesthesia values (P=0.0001), while isoflurane did not significantly alter cerebral blood flow (88.45% of baseline, P=0.39). Significant linear relationships between cerebral blood flow and CO₂ tension were determined in all individual studies (r2 ranged from 0.72 to 0.99). The slopes of the lines were highly variable between individuals for the awake cohort (mean 4.73, 1.42-7.12, 95% CI). The slopes for the propofol (mean 2.67, 2.06-3.28, 95% CI) and isoflurane (mean 2.82, 2.19-3.45, 95% CI) cohorts were more predictable. However, there was no significant difference between these anaesthetic agents with respect to the CO₂ reactivity of cerebral blood flow.J. A. Myburgh, R. N. Upton, G. L. Ludbrook, A. Martinez, C. Granthttp://www.aaic.net.au/Article.asp?D=200137

Response of Grape and Wine Phenolic Composition in Vitis vinifera L. cv. Merlot to Variation in Grapevine Water Status

Grape and wine phenolic composition was monitored over two consecutive seasons in Vitis vinifera cv. Merlotfollowing application of irrigation treatments that produced seasonal average stem water potentials rangingbetween -0.7 MPa and -1.4 MPa. Fresh weight of berries was significantly reduced in response to water deficit,primarily due to decreases in pericarp weight. Increases in the concentration of grape anthocyanins andflavonols in response to water deficit were found when expressed per unit grape berry fresh weight. Skin-derivedtannin concentration in grape berries was not affected by the irrigation treatments. The concentration of grapederivedphenolics was monitored during five days of fermentation in a small-lot winemaking experiment. Duringfermentation, the concentration of anthocyanins and flavonols in wine were highest in the non-irrigated and lowfrequency-irrigated treatments, which was reflected in changes in the wine colour of ferments. Finished winesfrom non-irrigated and low frequency irrigated grapevines showed increases in bisulphite-resistant pigmentswhen compared with those irrigated at a high frequency, but differences in phenolic composition were minor.Increases in bisulphite-resistant pigments were associated with increases in vitisin A and polymeric pigmentin the first and second seasons of the study respectively. Ageing of wines for an 18-month period increasedbisulphite-resistant pigments, and treatment differences in wine colour density were enhanced, such thatincreases in both parameters were associated with the non-irrigated and low-frequency-irrigated treatments

Inhibitor of serine peptidase 2 enhances Leishmania major survival in the skin through control of monocytes and monocyte-derived cells

Leishmania major is the causative agent of the neglected tropical disease, cutaneous leishmaniasis. In the mouse, protective immunity to Leishmania is associated with inflammatory responses. Here, we assess the dynamics of the inflammatory responses at the lesion site during experimental long-term, low-dose intradermal infection of the ear, employing noninvasive imaging and genetically modified L. major Significant infiltrates of neutrophils and monocytes occurred at 1-4 d and 2-4 wk, whereas dermal macrophage and dendritic cell (DC) numbers were only slightly elevated in the first days. Quantitative whole-body bioluminescence imaging of myeloperoxidase activity and the quantification of parasite loads indicated that the Leishmania virulence factor, inhibitor of serine peptidase 2 (ISP2), is required to modulate phagocyte activation and is important for parasite survival at the infection site. ISP2 played a role in the control of monocyte, monocyte-derived macrophage, and monocyte-derived DC (moDC) influx, and was required to reduce iNOS expression in monocytes, monocyte-derived cells, and dermal DCs; the expression of CD80 in moDCs; and levels of IFN-γ in situ. Our findings indicate that the increased survival of L. major in the dermis during acute infection is associated with the down-regulation of inflammatory monocytes and monocyte-derived cells via ISP2.-Goundry, A., Romano, A., Lima, A. P. C. A., Mottram, J. C., Myburgh, E. Inhibitor of serine peptidase 2 enhances Leishmania major survival in the skin through control of monocytes and monocyte-derived cells

Horizontal HIV transmission to children of HIV-uninfected mothers : a case series and review of the global literature

CITATION: Myburgh, D. et al. 2020. Horizontal HIV transmission to children of HIV-uninfected mothers: A case series and review of the global literature. International journal of infectious diseases, 98:315–320. doi:10.1016/j.ijid.2020.06.081The original publication is available at https://www.journals.elsevier.com/international-journal-of-infectious-diseasesBackground: Vertical transmission is the predominant route for acquisition of HIV infection in children, either in utero, intrapartum or postnatally through breast feeding. Less frequently, children may acquire HIV by horizontal transmission. Horizontal transmission may be healthcare-associated (infusion of HIV-contaminated blood products, use of contaminated needles, syringes and medical equipment, or through ingestion of HIV in expressed breastmilk). Community-acquired HIV transmission to children may occur following surrogate breastfeeding, pre-mastication of food, and sexual abuse. Methods: Children with suspected horizontally acquired HIV infection were identified by retrospective folder review of existing patients (2004–2014) and by prospective interview and examination of new patients (from 2009 onwards), at a hospital-based paediatric antiretroviral clinic in Cape Town, South Africa. The global literature on horizontal HIV transmission to children (1 January 1986–1 November 2019) was reviewed, to contextualize the local findings. Results: Among the 32 children with horizontal HIV transmission (15 identified retrospectively and 17 prospectively), the median age at first diagnosis was 79 months (interquartile range 28.5–91.5); most children (90.6%) had advanced HIV disease at presentation. HIV transmission was considered healthcare-associated in 15 (46.9%), community-associated in ten (31.3%), possibly healthcare or community-associated in five (15.6 %); and unknown in two children (6.3%). Conclusion: Horizontal HIV transmission to children is an important public health issue, with prevention efforts requiring intervention at healthcare facility- and community-level. Greater effort should be made to promptly identify and comprehensively investigate each horizontally HIV-infected child to establish possible routes of transmission and inform future prevention strategies.https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S120197122030521X?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS120197122030521X%3Fshowall%3Dtrue&referrer=Publishers versio

TB programme stakeholder views on lessons from the COVID-19 response in South Africa

BACKGROUND: The global COVID-19 pandemic has reversed many of the hard-won gains made in TB programmes and the associated reduction in the number of TB deaths, case notifications and incidence over the last three decades. Modelling estimates show that the impact will be lasting. There are global calls to recover the shortfalls along the TB care cascade that have resulted from COVID-19, with the recognition that the COVID-19 response holds lessons to inform more robust and comprehensive TB programmes and services. OBJECTIVE: To explore lessons from response measures to the COVID-19 pandemic in two high TB burden South African provinces. DESIGN: This was an exploratory qualitative study. We conducted interviews with TB programme stakeholders (managers and facility-level staff: n = 35) between February and June 2022. RESULTS: We identified eight facilitators of the COVID-19 response, including political will, rapid policy development, multi-sectoral collaboration, patient-centred models of care delivery, community engagement, mHealth and telehealth technologies, rigorous contact tracing and widespread mask wearing. Political will was singled out as a critical driver of the response. CONCLUSION: Leveraging COVID-19 inspired collaborations, technologies and avenues for health service delivery is an opportunity to maximise benefits for the TB programme. Reinvestment in national TB programmes and political prioritisation of TB are critical

Bench-to-bedside review: The evaluation of complex interventions in critical care

Complex interventions, such as the introduction of medical emergency teams or an early goal-directed therapy protocol, are developed from a number of components that may act both independently and inter-dependently. There is an emerging body of literature advocating the use of integrated complex interventions to optimise the treatment of critically ill patients. As with any other treatment, complex interventions should undergo careful evaluation prior to widespread introduction into clinical practice. During the development of an international collaboration of researchers investigating protocol-based approaches to the resuscitation of patients with severe sepsis, we examined the specific issues related to the evaluation of complex interventions. This review outlines some of these issues. The issues specific to trials of complex interventions that require particular attention include determining an appropriate study population and defining current treatments and outcomes in that population, defining the study intervention and the treatment to be used in the control group, and deploying the intervention in a standardised manner. The context in which the research takes place, including existing staffing levels and existing protocols and procedures, is crucial. We also discuss specific details of trial execution, in particular randomization, blinded outcome adjudication and analysis of the results, which are key to avoiding bias in the design and interpretation of such trials

Sex differences in pain expressed by patients across diverse disease states: individual patient data meta-analysis of 33,957 participants in 10 randomized controlled trials

The experience of pain is determined by many factors and has a significant impact on quality of life. This study aimed to determine sex differences in pain prevalence and intensity reported by participants with diverse disease states in several large international clinical trials. Individual participant data meta-analysis was conducted using EuroQol-5 Dimension (EQ-5D) questionnaire pain data from randomised controlled trials published between January 2000 and January 2020 and undertaken by investigators at the George Institute for Global Health. Proportional odds logistic regression models, comparing pain scores between females and males and fitted with adjustments for age and randomized treatment, were pooled in a random-effects meta-analysis. In 10 trials involving 33,957 participants (38% females) with EQ-5D pain score data, the mean age ranged between 50 and 74. Pain was reported more frequently by females than males (47% vs 37%; P < 0.001). Females also reported greater levels of pain than males (adjusted odds ratio 1.41, 95% CI 1.24-1.61; P < 0.001). In stratified analyses, there were differences in pain by disease group (P for heterogeneity <0.001), but not by age group or region of recruitment. Females were more likely to report pain, and at a higher level, compared with males across diverse diseases, all ages, and geographical regions. This study reinforces the importance of reporting sex-disaggregated analysis to identify similarities and differences between females and males that reflect variable biology and may affect disease profiles and have implications for management