"I want to see them thrive!": exploring health service research priorities for young Aboriginal children growing up in Alice Springs - a qualitative study.

To better understand the specific influences of early life on the long-term health and well-being of local Aboriginal children in Alice Springs, high-quality local longitudinal data is required. The Central Australian Aboriginal Congress and the Murdoch Children's Research Institute are exploring the feasibility of establishing a cohort study to fill this gap. A nested qualitative study was conducted to identify priority issues that can be translated into research questions answerable through the proposed cohort study. Semi-structured interviews and focus group discussions (FGDs) were conducted with a range of key community stakeholders, parents and caregivers of young Aboriginal children from Alice Springs in the Northern Territory between 2020 and 2021. Two Aboriginal and two non-Aboriginal researchers conducted 27 interviews and 3 FGDs with 42 participants. Three broad themes were constructed through reflexive thematic analysis representing the areas of focus community stakeholders and parents want future research to prioritise: (1) social determinants of health (2) building positive connections, and (3) making sure kids grow up strong and healthy. Priority setting for future research should be driven by Aboriginal and Torres Strait Islander peoples in order to be of practical benefit to their community. This qualitative study found that housing, transport and positive connections through nurturing and engaged parents were some of the most important issues raised. Participants also wanted future research to focus on issues specific to children such as nutrition, hearing loss, language development and capacity to learn. These findings will guide future work led by local Aboriginal researchers to co-design the proposed cohort study.

Developing research in partnership with Aboriginal communities - strategies for improving recruitment and retention.

CONTEXT: Australian Aboriginal communities in urban, rural and remote areas are continuing to suffer high rates of perinatal mortality and morbidity that will impact on the future health of the community. It has been well documented that Aboriginal women have extreme distrust of mainstream pregnancy-related health care and suggested that late entry into antenatal care is as high as 50% in the Aboriginal population. Although medical and midwifery staff have long discussed strategies to improve uptake of antenatal health care for Aboriginal women, researchers in many areas have found the recruitment of Aboriginal people into scientific studies almost impossible. This article seeks to share the strategies that have been developed over a period of time by the authors that have proved useful for recruitment and retention into research. It is anticipated that these strategies would also apply for health practitioners in maintaining their patients for clinical care management. ISSUE: Although each research location (regional, rural and remote) has had to spend time determining what approach is best for meeting the research outcomes, many of these suggestions become applicable to clinicians seeking to develop better connections with Aboriginal patients in their clinics. With the management of ongoing chronic health conditions for Aboriginal people a priority in 'Closing the Gap', a number of these suggestions could easily be implemented by clinicians. Remembering that each community has specific needs that must be addressed, priorities for assistance for that community will be easily identifiable after community consultation (eg transport, or ability to access medical testing). Opportunities for the use of new social media (eg Facebook) as communication tools for researchers and clinicians will have increasing applicability as further software updates are created. LESSONS LEARNT: With open and trusting dialogues between researchers, clinicians and Aboriginal communities, we can go a long way towards understanding the needs of individual communities and working in partnerships to close the gap.

Psychological Distress, Stressful Life Events and Social Disadvantage in Pregnant Indigenous Australian Women Residing in Rural and Remote NSW: a Longitudinal Cohort Study.

BACKGROUND: Pregnancy can be a stressful time for many women. Australian Indigenous women of childbearing age (18-44 years) have been found to experience high or very high rates of psychological distress. However, few studies have examined the burden of or any associations between stressful life events, social disadvantage and psychological distress for pregnant Indigenous women in Australia. METHODS: Two hundred sixty-one rural and remote women, pregnant with an Indigenous infant, from New South Wales in Australia were invited to provide data regarding social disadvantage then complete the Kessler-10 and Stressful Life Events surveys via self-report during each trimester of their pregnancy. Descriptive statistics, Pearson's correlations, Mann-Whitney U and Kruskal-Wallis tests were performed to determine the burden of and any associations between the variables of interest. RESULTS: High rates of psychological distress were reported by participants with 16.9% scoring severe distress levels during their pregnancy. Participants also reported high rates of stressful life events with almost 25% experiencing the death of a family member or friend, almost 14% living in overcrowded accommodation, 11% having someone close to them jailed and 8% experience separation from their partner, during their pregnancies. Distress was associated with numerous stressful life events (e.g. witnessing violence, a family member in jail and overcrowding) and one aspect of social disadvantage (smoking status). CONCLUSIONS: Immediate attention needs to focus on the development of interventions to address the high levels of psychological distress and provide appropriate support services during periods of major life events for pregnant Australian Indigenous women.

Identifying young Aboriginal and Torres Strait Islander children in linked administrative data: A comparison of methods.

BACKGROUND: In the ongoing debate on optimum methods for identification of Indigenous people within linked administrative data, few studies have examined the impacts of method on population counts and outcomes in family-based linkage studies of Aboriginal children. OBJECTIVE: To quantify differences between three algorithms in ascertaining Aboriginal and Torres Strait Islander children in linked administrative data. METHODS: Linked administrative health data for children born in Western Australia (WA) from 2000-2013, were used to examine the cohorts identified by three methods: A) the Indigenous Status Flag (ISF, derived by the WA Data Linkage Branch using a multistage-median approach) for the children alone; B) the ISF of the children, their parents and grandparents; and C) Indigenous status of the child, mother or father on either of the child's perinatal records (Midwives or birth registration), to determine differing characteristics of each cohort. RESULTS: Method B established a larger cohort (33,489) than Method C (33,306) and Method A (27,279), with all methods identifying a core group of 26,790 children (80-98%). Compared with children identified by Method A, additional children identified by Methods B or C, were from less-disadvantaged and more urban areas, and had better perinatal outcomes (e.g. lower proportions of small-for-gestational age, 10% vs 16%). Differences in demographics and health outcomes between Methods C and B were minimal. CONCLUSIONS: Demographic and perinatal health characteristics differ by Aboriginal identification method. Using perinatal records or the ISF of parents and grandparents (in addition to the ISF of the child) appear to be more inclusive methods for identifying young Indigenous children in administrative datasets. KEYWORDS: Aboriginal health, identification, data linkage, Indigenous, child, methodology.

Plasma and pulmonary fluid endothelin in horses with seasonal recurrent airway obstruction.

BACKGROUND: Summer pasture-associated recurrent airway obstruction (SPA-RAO), a seasonal airway obstructive disease of horses, is characterized by clinical exacerbation after exposure to pasture during warm months of the year. Endothelin (ET)-1, potent bronchoconstrictor, mitogen, secretagogue, and proinflammatory mediator, has been implicated in the pathogenesis of asthma and equine heaves. HYPOTHESIS: Immunoreactive ET-1 concentrations increase during clinical exacerbation and return to basal values during periods of disease remission. ANIMALS: Twelve horses, 6 affected with SPA-RAO and 6 nonaffected. METHODS: Prospective, observational study. Bronchoalveolar lavage fluid (BALF), arterial and venous plasma samples, and clinical variables were obtained from affected horses during clinical exacerbation and remission. Samples and data of nonaffected horses were collected during the summer and winter on dates similar to affected horses. Immunoreactive ET-1 was determined using a commercial ELISA. RESULTS: The median and range ET-1 concentrations (pg/ml) in arterial (1.3, 0.7-1.8) and venous (1.3, 1.2-1.7) plasma and in BALF (0.3, 0.2-0.4), and pulmonary epithelial lining fluid (PELF) (25.5, 21-50) were greater in affected horses during clinical exacerbation compared with remission (P < .01). The concentrations of immunoreactive ET-1 were greater in affected horses during clinical exacerbation compared with nonaffected horses (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: During clinical exacerbation of SPA-RAO, ET-1 is increased in circulation and pulmonary secretions. Intervention with ET receptor antagonists should provide further information on the role of ET-1 in SPA-RAO.

Identifying pregnant women at risk of poor birth outcomes.

Pregnancy is a vulnerable period in women's lives, with a range of maternal and environmental factors impacting upon pregnancy outcome. This study sought to explore the clustering of health risks among pregnant women, and compare the characteristics of women exhibiting clustered risks. A cross-sectional study was undertaken at a large public hospital in Queensland, Australia. Cluster analysis grouped women who had similar levels of risk based on health and lifestyle factors demonstrated to be associated with adverse maternal and infant outcomes. Interviews were conducted with 437 women. The results highlight the interconnectedness of demographic and health risks, and high concentration of risks among Indigenous women. Vulnerable women can be identified and targeted for public health interventions focussing on clustered risk factors, such as alcohol, smoking and sexually transmitted infections. Opportunity exists for screening in routine primary care to identify the individuals who are at risk, rather than identifying specific risks.

Ex vivo effects of insulin on the structural integrity of equine digital lamellae.

BACKGROUND: Laminitis has a considerable impact on the equine industry. Endocrinopathic laminitis is the most common form and affected horses often have hyperinsulinaemia due to an underlying metabolic disorder. OBJECTIVES: The aim of this study was to determine if insulin weakens the structural integrity of digital lamellae and to develop an ex vivo model for the study of hyperinsulinaemia-induced lamellar failure. STUDY DESIGN: Ex vivo experiment. METHODS: Biomechanical testing was used to assess the structural integrity of lamellar explants exposed to either medium alone (control) or medium supplemented with insulin. Lamellar explants comprised of hoof wall, lamellar tissue and distal phalanx were harvested from four adult horses with no evidence of inflammatory disease or pre-existing disease of the digit. Following an equilibration period, explants were incubated in medium or medium supplemented with insulin (2.5 µg/ml) for 8 h prior to biomechanical testing to obtain load (N), stress (MPa), elongation to failure (mm), and Young's modulus (MPa) for each explant. Significant differences were assessed using a mixed linear model with horses as a random factor and control or insulin-treated group as a fixed factor. RESULTS: Lamellar explants incubated in medium supplemented with insulin failed at significantly lower load (P = 0.0001) and lower stress (P = 0.001) and had greater elongation to failure (P = 0.02). MAIN LIMITATIONS: In addition to the ex vivo nature of the study, location-dependent variability in explant structural integrity and variable diffusion of nutrients due to explant size may have been limitations. However, the study design attempted to account for these limitations through random assignment of explants to treatment groups independent of location and by evaluating stress to failure. CONCLUSIONS: Insulin weakens the structural integrity of equine lamellar explants and an ex vivo model for evaluation of hyperinsulinaemia-induced lamellar failure was established. The summary is available in Spanish - see Supporting Information.

Sleep influences on cardio-metabolic health in Indigenous populations.

Indigenous populations continue to be among the world's most marginalized population groups. Studies in Indigenous populations from high income countries (including the United States, Canada, Australia, and New Zealand) indicate increased risk of sleep disorders compared to non-Indigenous populations. Poor sleep, whether it be short sleep duration or fragmented sleep, is a well-established risk factor for cardio-metabolic diseases. Given the implications, targeted improvement of poor sleep may be beneficial for the health and well-being of Indigenous people. In this narrative review, we will: (1) discuss the effects of sleep on the cardio-metabolic processes; (2) examine sleep in Indigenous populations; (3) review the association between sleep and cardio-metabolic risk in Indigenous populations; and (4) review the potential role of sleep in cardiovascular disease risk detection and interventions to improve sleep and cardio-metabolic health in Indigenous people. In particular, this review highlights that the assessment of sleep quality and quantity may be a beneficial step toward identifying Indigenous people at risk of cardio-metabolic diseases and may represent a key intervention target to improve cardio-metabolic outcomes.

Pregnancy stress, healthy pregnancy and birth outcomes - the need for early preventative approaches in pregnant Australian Indigenous women: a prospective longitudinal cohort study.

Adverse pregnancy outcomes including prematurity and low birth weight (LBW) have been associated with life-long chronic disease risk for the infant. Stress during pregnancy increases the risk of adverse pregnancy outcomes. Many studies have reported the incidence of adverse pregnancy outcomes in Indigenous populations and a smaller number of studies have measured rates of stress and depression in these populations. This study sought to examine the potential association between stress during pregnancy and the rate of adverse pregnancy outcomes in Australian Indigenous women residing in rural and remote communities in New South Wales. This study found a higher rate of post-traumatic stress disorder, depression and anxiety symptoms during pregnancy than the general population. There was also a higher incidence of prematurity and LBW deliveries. Unfortunately, missing post-traumatic stress disorder and depressive symptomatology data impeded the examination of associations of interest. This was largely due to the highly sensitive nature of the issues under investigation, and the need to ensure adequate levels of trust between Indigenous women and research staff before disclosure and recording of sensitive research data. We were unable to demonstrate a significant association between the level of stress and the incidence of adverse pregnancy outcomes at this stage. We recommend this longitudinal study continue until complete data sets are available. Future research in this area should ensure prioritization of building trust in participants and overestimating sample size to ensure no undue pressure is placed upon an already stressed participant.

Influence of maternal adiposity, preterm birth and birth weight centiles on early childhood obesity in an Indigenous Australian pregnancy-through-to-early-childhood cohort study.

Childhood obesity rates are higher among Indigenous compared with non-Indigenous Australian children. It has been hypothesized that early-life influences beginning with the intrauterine environment predict the development of obesity in the offspring. The aim of this paper was to assess, in 227 mother-child dyads from the Gomeroi gaaynggal cohort, associations between prematurity, Gestation Related-Optimal Weight (GROW) centiles, maternal adiposity (percentage body fat, visceral fat area), maternal non-fasting plasma glucose levels (measured at mean gestational age of 23.1 weeks) and offspring BMI and adiposity (abdominal circumference, subscapular skinfold thickness) in early childhood (mean age 23.4 months). Maternal non-fasting plasma glucose concentrations were positively associated with infant birth weight (P=0.005) and GROW customized birth weight centiles (P=0.008). There was a significant association between maternal percentage body fat (P=0.02) and visceral fat area (P=0.00) with infant body weight in early childhood. Body mass index (BMI) in early childhood was significantly higher in offspring born preterm compared with those born at term (P=0.03). GROW customized birth weight centiles was significantly associated with body weight (P=0.01), BMI (P=0.007) and abdominal circumference (P=0.039) at early childhood. Our findings suggest that being born preterm, large for gestational age or exposed to an obesogenic intrauterine environment and higher maternal non-fasting plasma glucose concentrations are associated with increased obesity risk in early childhood. Future strategies should aim to reduce the prevalence of overweight/obesity in women of child-bearing age and emphasize the importance of optimal glycemia during pregnancy, particularly in Indigenous women.

Lamellar events related to insulin-like growth factor-1 receptor signalling in two models relevant to endocrinopathic laminitis.

BACKGROUND: Insulin dysregulation, obesity, and exposure to high-nonstructural carbohydrate (NSC) forage are risk factors for equine metabolic syndrome-associated laminitis (EMSAL); high systemic insulin concentrations in EMSAL are proposed to induce cellular dysregulation in the digital lamellae through activation of the insulin-like growth factor-1 receptor. OBJECTIVES: To use a dietary challenge model (DCM) and a euglycaemic-hyperinsulinaemic clamp (EHC) model to assess lamellar growth factor-related signalling. STUDY DESIGN: Lamellar phospho (P)-protein concentrations of signalling proteins important in growth factor-related signalling were assessed in 2 models: 1) lean and obese ponies on a low- or high-NSC diet; and 2) EHC model using Standardbred horses. METHODS: Ponies stratified for body condition (lean [LN, n = 11] and obese [OB, n = 11]) were exposed to a low-NSC diet (LO, n = 5 per group for LN LO and OB LO) or a high NSC diet (HI, n = 6 per group for LN HI and OB HI groups) for 7 days. For the EHC model, horses were administered insulin (constant rate infusion [6 mIU/kg bwt/min] combined with 50% dextrose, EHC group, n = 8)] or saline (0.57 mL/kg bwt/h, CON group, n = 8) for 48 h. Immunoblotting was employed to assess concentrations of activated/phosphorylated and total protein for members of the PI3K/Akt/mTORC1 and Ras/ERK pathways in lamellar samples from both models. RESULTS: In the DCM, lamellar P-(Ser 240/244) RPS6 was increased in OB HI ponies (vs. OB LO, P<0.05); positive correlations existed (P<0.05; r>0.5) between Day 7 basal serum insulin concentrations and lamellar concentrations of P-p70S6K and P-(Ser 240/244) RPS6. In the EHC model, lamellar concentrations of P-Akt, P-p70S6K, P-ERK 1/2, P-p90RSK, and both P-(Ser 235/236) and P-(Ser 240/244) RPS6 were increased in the EHC group (vs. CON, P<0.05). MAIN LIMITATIONS: The primary limitations of this study are the small number of animals per group in the DCM study, and the fact that many animals did not develop laminitis as that was not the endpoint of either study. CONCLUSIONS: These results support further investigation of mTORC1/RPS6 signalling as a potential therapeutic target(s) in EMSAL. The Summary is available in Chinese - see Supporting Information.

Evaluation of cefotaxime alone and in combination with desacetylcefotaxime against strains of Staphylococcus aureus that produce variants of staphylococcal beta-lactamase.

We evaluated cefotaxime (CTX) alone and in combination with its metabolite, desacetylcefotaxime (dCTX) against strains of Staphylococcus aureus that produce the four recognized variants of staphylococcal beta-lactamase and a beta-lactamase-producing isolate characterized by the expression of borderline resistance to methicillin. Although macrodilution MICs revealed that dCTX was less active than CTX against these strains (geometric means of 16 micrograms/ml and 4 micrograms/ml, respectively), the addition of clinically achievable concentrations of dCTX to CTX resulted in a reduction in the observed CTX MICs. This effect was similar to although less pronounced than that obtained by combining clavulanic acid with cefazolin. The increased antistaphylococcal activity noted by MIC determinations was confirmed with kill-kinetic studies. Determination of the relative rates of hydrolysis of selected cephalosporins showed that neither CTX nor dCTX were appreciably hydrolyzed by the variant staphylococcal enzymes. Evaluation of the effect of CTX and dCTX upon the staphylococcal beta-lactamases demonstrated that neither agent inhibited the destruction of a 100 microM solution of nitrocefin, although the reduction of CTX and cefazolin MICs by low concentrations of dCTX suggests that the dCTX metabolite may act as a competitive inhibitor of beta-lactamase. These observations may explain the previously demonstrated clinical efficacy of CTX used alone for the treatment of serious infections caused by S. aureus.

Pharmacokinetics of naratriptan in adolescent subjects with a history of migraine.

Naratriptan is a novel 5-HT1 agonist developed to treat acute migraine. The study objective was to characterize the pharmacokinetics of oral naratriptan in adolescent migraine patients outside a migraine attack. Subjects received a single 2.5 mg naratriptan tablet. Serial serum samples for naratriptan concentrations were collected over 24 hours. Blood pressure, pulse rate, and 12-lead ECG were recorded at baseline and at regular intervals after dosing. Seven patients--3 males and 4 females, 12 to 16 years of age--received drug and completed the study. The geometric mean and 95% confidence interval maximum concentration (Cmax) was 8.0 ng/mL (5.9-10.7), elimination half-life (t1/2) was 4.9 hours (4.5-5.4), area under the concentration-time curve (AUC) was 74.6 ng.h/mL (56.6-98.2), and apparent total clearance (Cl/F) was 558.8 mL/min (424.3-735.9). The median time to maximal concentration (tmax) was 4 hours, with a range of 1.5 to 4. Blood pressure, pulse rate, and ECG parameters did not change significantly from baseline. No serious adverse events or subject withdrawal after drug administration occurred. Oral naratriptan pharmacokinetic parameters in adolescents were similar to values reported in adults. Naratriptan doses for adolescents older than 12 years of age would be expected to be similar to adult doses.

Disseminated, multiclonal Epstein-Barr virus-associated lymphoproliferative disease in a patient with hematological and immunological anomalies. Molecular analysis correlates with morphological appearance.

We report a case of a 21-year-old woman with hematopoietic, immunological, and congenital dysmorphic abnormalities, who died following rapidly progressive, disseminated Epstein-Barr virus (EBV)-associated lymphoproliferative disease (LPD). Polymerase chain reaction (PCR) amplification of formalin-fixed paraffin-embedded tissue showed differences in the clonality of each separate lymphoproliferative lesion examined, as determined by immunoglobulin heavy chain (IgH) gene rearrangement. PCR analysis also demonstrated that all lesions contained EBV genome. Since DNA had been extracted from paraffin blocks, a direct comparison of morphology and clonality could be made in each individual lesion. The evidence from this study indicates that the monoclonal tumors arose de novo in multiple sites and that the polyclonal background observed in some lesions reflected a substantial concomitant inflammatory response.

Factors determining the susceptibility of mice to experimental phycomycosis.

Various factors influencing the susceptibility of C3H mice to lethal infection by the phycomycete Absidia ramosa were examined. Mice 19-21 days old were exposed to graded doses of A. ramosa spores by various routes. After intravenous inoculation with doses in excess of 10(3) viable units, a variable proportion of mice developed lethal phycomycosis of the central nervous system within 2-8 days. The proportion of mice affected was related to the inoculum size, doses of 5 X 10(7) spores producing lethal infection in 90-100% of the mice. The disease was characterised by signs of involvement of the central nervous system appearing 8-12 h before death. At necropsy, fungal hyphae, frequently surrounded by infiltrations of mononuclear cells, could be demonstrated in the brain. Lesions were also often present in the kidneys; in other organs they were rare, but the presence of viable fungal spores could be detected by cultural procedures. Subcutaneous inoculation of A. ramosa spores did not produce lethal infection but intraperitoneal inoculation occasionally did so. Direct intracerebral inoculation invariably produced lethal infection even with very small doses of spores. The clinical and histopathological features of the disease were almost identical with those resulting from intravenous inoculation. Pre-inoculation treatment with azathioprine, cyclophosphamide and antithymocyte serum did not increase susceptibility. Susceptibility was increased by injections of zymosan, aggregared gamma-globulin, cortisone acetate and Fe(II) salts and by reticuloendothelial blockade. These treatments increased the proportion of mice developing lethal phycomycosis of the central nervous system, and in the case of cortisone acetate, also promoted disseminated infection. It was concluded that the natural resistance of mice to A. ramosa infection was probably dependent upon the activity of phagocytic cells, possibly acting in conjunction with complement and other non-specific serum factors.

Endotoxaemia in dairy cattle: mechanism of reticulorumen stasis.

The objective of this study was to determine whether blockade of alpha(-2) adrenergic receptors would restore reticulorumen motility during toxaemia in cows. Reticulorumen contractions were measured via a water-filled balloon connected to a pressure transducer. Intravenous infusion of endotoxin (100 ng kg-1 over 30 min) significantly decreased the number of reticulorumen contractions. Intravenous infusion of yohimbine (125 micrograms kg-1 over 30 min) alone did not affect reticulorumen contractions. However, when yohimbine (125 micrograms kg-1 over 30 min) was infused concurrently with endotoxin (100 ng kg-1 over 30 min), the effects of endotoxin on reticulorumen contraction frequency decreased, suggesting that endotoxaemia causes reticulorumen stasis via a mechanism that involves alpha(-2) adrenergic receptors.

Evidence for vascular and enzymatic events in the pathophysiology of acute laminitis: which pathway is responsible for initiation of this process in horses?

To date, there is a substantial amount of data to support the hypotheses that vascular and enzymatic changes are ongoing in experimental laminitis. Furthermore, there is substantial in vitro evidence that the enzymatic changes weaken the dermo-epidermal attachments leading to mechanical failure of the hoof-bone interface of the equine digit. However, investigators of both the vascular and enzymatic theories have, to date, been unable to substantiate the effects of these pathophysiological changes in vivo on laminar tissues of horses afflicted with experimentally induced or naturally acquired laminitis. In addition, the effects of laminitis-inducing treatment have not been prevented or reversed by treatment with an MMP inhibitor or a vasoactive antagonist. It is possible that there is simultaneous activation of the vascular and enzymatic pathways and/or other inflammatory processes. Moreover, the third theory involving mechanical factors cannot be discounted simply because strong evidence for vascular and enzymatic changes exists. It is common for horses with severe musculoskeletal disease affecting weightbearing on a limb to develop laminitis in the contralateral limb. It remains to be determined what factors are responsible for initiation of laminitis in these individuals. Evidence has not been presented that precludes the possibility of coincident occurrence of vascular and enzymatic changes. In fact, many of the inflammatory mediators (e.g. interleukin-1beta) found in laminitic tissues can concurrently stimulate synthesis of vasoactive substances and activate MMPs. Because enzymatic action on proteins is largely dependent on the concentrations of proteins and enzyme, the enzymatic theory is not dependent upon increased delivery of enzymes via increased capillary flow. Likewise, because vascular changes can alter tissue function via increased capillary flow and oedema formation, the vascular theory is not dependent upon decreased capillary flow. It is true that naturally acquired laminitis is widely variable in severity and predisposing diseases. Therefore, most probably there are multiple mechanisms involved in the initiation and propagation of the pathophysiologic cascade(s) and, therefore, successful intervention will necessitate multiple treatment modalities.

Cardiopulmonary, blood and peritoneal fluid alterations associated with abdominal insufflation of carbon dioxide in standing horses.

REASONS FOR PERFORMING STUDY: Abdominal insufflation is performed routinely during laparoscopy in horses to improve visualisation and facilitate instrument and visceral manipulations during surgery. It has been shown that high-pressure pneumoperitoneum with carbon dioxide (CO2) has deleterious cardiopulmonary effects in dorsally recumbent, mechanically ventilated, halothane-anaesthetised horses. There is no information on the effects of CO2 pneumoperitoneum on cardiopulmonary function and haematology, plasma chemistry and peritoneal fluid (PF) variables in standing sedated horses during laparoscopic surgery. OBJECTIVES: To determine the effects of high pressure CO2 pneumoperitoneum in standing sedated horses on cardiopulmonary function, blood gas, haematology, plasma chemistry and PF variables. METHODS: Six healthy, mature horses were sedated with an i.v. bolus of detomidine (0.02 mg/kg bwt) and butorphanol (0.02 mg/kg bwt) and instrumented to determine the changes in cardiopulmonary function, haematology, serum chemistry and PF values during and after pneumoperitoneum with CO2 to 15 mmHg pressure for standing laparoscopy. Each horse was assigned at random to either a standing left flank exploratory laparoscopy (LFL) with CO2 pneumoperitoneum or sham procedure (SLFL) without insufflation, and instrumented for measurement of cardiopulmonary variables. Each horse underwent a second procedure in crossover fashion one month later so that all 6 horses had both an LFL and SLFL performed. Cardiopulmonary variables and blood gas analyses were obtained 5 mins after sedation and every 15 mins during 60 mins baseline (BL), insufflation (15 mmHg) and desufflation. Haematology, serum chemistry analysis and PF analysis were performed at BL, insufflation and desufflation, and 24 h after the conclusion of each procedure. RESULTS: Significant decreases in heart rate, cardiac output and cardiac index and significant increases in mean right atrial pressure, systemic vascular resistance and pulmonary vascular resistance were recorded immediately after and during sedation in both groups of horses. Pneumoperitoneum with CO2 at 15 mmHg had no significant effect on cardiopulmonary function during surgery. There were no significant differences in blood gas, haematology or plasma chemistry values within or between groups at any time interval during the study. There was a significant increase in the PF total nucleated cell count 24 h following LFL compared to baseline values for LFL or SLFL at 24 h. There were no differences in PF protein concentrations within or between groups at any time interval. CONCLUSIONS: Pneumoperitoneum with CO2 during standing laparoscopy in healthy horses does not cause adverse alterations in cardiopulmonary, haematology or plasma chemistry variables, but does induce a mild inflammatory response within the peritoneal cavity. POTENTIAL RELEVANCE: High pressure (15 mmHg) pneumoperitoneum in standing sedated mature horses for laparoscopic surgery can be performed safely without any short-term or cumulative adverse effects on haemodynamic or cardiopulmonary function.

Blockade of endotoxin-induced cecal hypoperfusion and ileus with an alpha 2 antagonist in horses.

Stimulation of alpha 2 adrenergic receptors inhibits colonic motility and may constrict some peripheral vascular beds. Endotoxemia elicits release of sympathetic neurotransmitters and increases sympathetic nerve activity, which may result in stimulation of alpha 2 adrenergic receptors. The objective of this study was to determine whether blockade of alpha 2 adrenergic receptors would restore cecal motility and blood flow during endotoxemia in horses. Strain-gauge force transducers and ultrasonic flow probes were used to measure cecal and colonic mechanical activity and lateral cecal arterial blood flow. Intravenous infusion of endotoxin (cumulative dose of 0.03 mg/kg) significantly decreased cecal and right ventral colon contractile activity and lateral cecal arterial blood flow. Slow IV infusion of yohimbine (cumulative dose of 75 micrograms/kg) significantly attenuated those effects of endotoxin. On the basis of our findings, we concluded that endotoxemia causes cecal and proximal colonic ileus and cecal hypoperfusion via a mechanism that involves alpha 2 adrenergic receptors.

Antagonism of a specific dopaminergic receptor agonist with metoclopramide in horses.

Changes in lateral cecal arterial blood flow, mean internal carotid arterial pressure, and heart rate caused by nasogastric administration of fenoldopam (3, 6, and 9 mg/kg of body weight), a selective agonist of dopaminergic receptors, were recorded in 7 healthy horses. Cecal arterial blood flow was significantly increased within 30 minutes after administration of fenoldopam at all 3 dosages, with the peak increases from baseline (67.8 +/- 17.5 ml/min) being 125 +/- 28, 120 +/- 22, and 153 +/- 32 ml/min for 3, 6, and 9 mg/kg, respectively. Although carotid arterial pressure did not change significantly after administration of fenoldopam at the dosage of 3 mg/kg, administration of fenoldopam at the dosages of 6 and 9 mg/kg significantly reduced carotid arterial pressure from 113 +/- 10 to 88 +/- 3 and 81 +/- 5 mm of Hg, respectively. Intravenous infusion of metoclopramide, a dopaminergic receptor antagonist, at the rate of 0.125 mg/kg/h, blocked the effect of fenoldopam on cecal arterial blood flow and carotid arterial pressure. It was concluded that dopaminergic receptors mediate alterations in local blood flow and systemic pressure in horses.