Combined transplantation of the heart and liver

The technique of combined transplantation of the heart and liver is described and illustrated, emphasizing modifications that were used in a successful case. Two other unsuccessful attempts are reported, and the importance of relative size of donor and recipient is discussed. There may be an immunological advantage to transplanting two organs in combination from the same donor

Techniques for combined procurement of hearts and kidneys with satisfactory early function of renal allografts.

Methods for combination of donor nephrectomy with donor cardiectomy are outlined. The satisfactory early function of 29 of 34 transplanted kidneys harvested with these techniques supports their wider application and should encourage their wider acceptance

Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy

Post-transplant lymphomas or other lymphoproliferative lesions, which were usually associated with Epstein-Barr virus infections, developed in 8, 4, 3, and 2 recipients, respectively, of cadaveric kidney, liver, heart, and heart-lung homografts. Reduction or discontinuance of immunosuppression caused regression of the lesions, often without subsequent rejection of the grafts. Chemotherapy and irradiation were not valuable. The findings may influence policies about treating other kinds of post-transplantation neoplasms

Veno-venous bypass without systemic anticoagulation for transplantation of the human liver

A technique of veno-venous bypass without heparin has been developed for use during the anhepatic phase of transplantation of the liver. With this method, the ability to compress the temporarily obstructed vena caval and portal venous systems has made hepatic transplantation an easier procedure

Advantages of venous bypass during orthotopic transplantation of the liver.

Venous bypass restores normal hemodynamic physiology during the critical anhepatic phase of orthotopic transplantation of the liver. Its routine use in adults undergoing transplantation in Pittsburgh has resulted in lower operative blood losses, a lower frequency of postoperative renal failure, and a greater probability of survival for all but the highest risk patients. Because it allows for a longer anhepatic phase, the surgeon has the option of tailoring the native hepatectomy to the needs of the individual case, even to the point, in difficult cases, of obtaining most of the hemostasis after removal of the native liver, but before sewing in the donor organ. Selective use of bypass in children may offer similar advantages

HEART-LIVER TRANSPLANTATION IN A PATIENT WITH FAMILIAL HYPERCHOLESTEROLAEMIA

A girl aged 6 years 9 months with severe heart disease secondary to homozygous familial hypercholesterolaemia underwent orthotopic cardiac transplantation and her liver was replaced with the liver of the same donor. In the first 10 weeks after transplantation serum cholesterol fell to 270 mg/dl from preoperative concentrations of more than 1000 mg/dl. © 1984

Full Genome Characterization of the Culicoides-Borne Marsupial Orbiviruses: Wallal Virus, Mudjinbarry Virus and Warrego Viruses

Viruses belonging to the species Wallal virus and Warrego virus of the genus Orbivirus were identified as causative agents of blindness in marsupials in Australia during 1994/5. Recent comparisons of nucleotide (nt) and amino acid (aa) sequences have provided a basis for the grouping and classification of orbivirus isolates. However, full-genome sequence data are not available for representatives of all Orbivirus species. We report full-genome sequence data for three additional orbiviruses: Wallal virus (WALV); Mudjinabarry virus (MUDV) and Warrego virus (WARV). Comparisons of conserved polymerase (Pol), sub-core-shell 'T2' and core-surface 'T13' proteins show that these viruses group with other Culicoides borne orbiviruses, clustering with Eubenangee virus (EUBV), another orbivirus infecting marsupials. WARV shares <70% aa identity in all three conserved proteins (Pol, T2 and T13) with other orbiviruses, consistent with its classification within a distinct Orbivirus species. Although WALV and MUDV share <72.86%/67.93% aa/nt identity with other orbiviruses in Pol, T2 and T13, they share >99%/90% aa/nt identities with each other (consistent with membership of the same virus species - Wallal virus). However, WALV and MUDV share <68% aa identity in their larger outer capsid protein VP2(OC1), consistent with membership of different serotypes within the species - WALV-1 and WALV-2 respectively

Impact of intravenous fluid composition on outcomes in patients with systemic inflammatory response syndrome

Introduction: Intravenous (IV) fluids may be associated with complications not often attributed to fluid type. Fluids with high chloride concentrations such as 0.9 % saline have been associated with adverse outcomes in surgery and critical care. Understanding the association between fluid type and outcomes in general hospitalized patients may inform selection of fluid type in clinical practice. We sought to determine if the type of IV fluid administered to patients with systemic inflammatory response syndrome (SIRS) is associated with outcome. Methods: This was a propensity-matched cohort study in hospitalized patients receiving at least 500 mL IV crystalloid within 48 hours of SIRS. Patient data was extracted from a large multi-hospital electronic health record database between January 1, 2009, and March 31, 2013. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay, readmission, and complications measured by ICD-9 coding and clinical definitions. Outcomes were adjusted for illness severity using the Acute Physiology Score. Of the 91,069 patients meeting inclusion criteria, 89,363 (98 %) received 0.9 % saline whereas 1706 (2 %) received a calcium-free balanced solution as the primary fluid. Results: There were 3116 well-matched patients, 1558 in each cohort. In comparison with the calcium-free balanced cohort, the saline cohort experienced greater in-hospital mortality (3.27 % vs. 1.03 %, P <0.001), length of stay (4.87 vs. 4.38 days, P = 0.016), frequency of readmission at 60 (13.54 vs. 10.91, P = 0.025) and 90 days (16.56 vs. 12.58, P = 0.002) and frequency of cardiac, infectious, and coagulopathy complications (all P <0.002). Outcomes were defined by administrative coding and clinically were internally consistent. Patients in the saline cohort received more chloride and had electrolyte abnormalities requiring replacement more frequently (P <0.001). No differences were found in acute renal failure. Conclusions: In this large electronic health record, the predominant use of 0.9 % saline in patients with SIRS was associated with significantly greater morbidity and mortality compared with predominant use of balanced fluids. The signal is consistent with that reported previously in perioperative and critical care patients. Given the large population of hospitalized patients receiving IV fluids, these differences may confer treatment implications and warrant corroboration via large clinical trials. Trial registration: NCT02083198 clinicaltrials.gov; March 5, 201

A bi-directional relationship between obesity and health-related quality of life : evidence from the longitudinal AusDiab study

Objective: To assess the prospective relationship between obesity and health-related quality of life, including a novel assessment of the impact of health-related quality of life on weight gain.Design and setting: Longitudinal, national, population-based Australian Diabetes, Obesity and Lifestyle (AusDiab) study, with surveys conducted in 1999/2000 and 2004/2005.Participants: A total of 5985 men and women aged 25 years at study entry.Main outcome measure(s): At both time points, height, weight and waist circumference were measured and self-report data on health-related quality of life from the SF-36 questionnaire were obtained. Cross-sectional and bi-directional, prospective associations between obesity categories and health-related quality of life were assessed.Results: Higher body mass index (BMI) at baseline was associated with deterioration in health-related quality of life over 5 years for seven of the eight health-related quality of life domains in women (all P0.01, with the exception of mental health, P&gt;0.05), and six out of eight in men (all P&lt;0.05, with the exception of role-emotional, P=0.055, and mental health, P&gt;0.05). Each of the quality-of-life domains related to mental health as well as the mental component summary were inversely associated with BMI change (all P&lt;0.0001 for women and P0.01 for men), with the exception of vitality, which was significant in women only (P=0.008). For the physical domains, change in BMI was inversely associated with baseline general health in women only (P=0.023).Conclusions: Obesity was associated with a deterioration in health-related quality of life (including both physical and mental health domains) in this cohort of Australian adults followed over 5 years. Health-related quality of life was also a predictor of weight gain over 5 years, indicating a bi-directional association between obesity and health-related quality of life. The identification of those with poor health-related quality of life may be important in assessing the risk of future weight gain, and a focus on health-related quality of life may be beneficial in weight management strategies.<br /

Regulation of Drosophila intestinal regeneration by the Hippo pathway

Intestinal stem cells (ISCs) in the adult Drosophila midgut proliferate in order to self-renew and produce differentiating daughter cells that replace those lost as part of normal gut function. Intestinal stress induces the activation of Upd/Jak/Stat signalling, which promotes intestinal regeneration by inducing rapid SC proliferation and faster tissue turnover. I have investigated the role of the Hippo (Hpo) pathway in the Drosophila midgut. The Hpo pathway regulates tissue size via the control of both apoptosis and proliferation during Drosophila development. In the midgut, Hpo pathway inactivation in either the SCs or their differentiated daughter cells, the enterocytes (ECs), induces a phenotype similar to that observed under stress situations, including increased proliferation and expression of Upd cytokines. Hpo pathway targets are induced by stresses such as bacterial infection, suggesting that the pathway functions as a sensor of cellular stress in the ECs. In addition, Yki, the pro-growth transcription factor target of the pathway, is required in ISCs to drive the proliferative response to stress. Yki inactivation has no obvious effect on baseline homeostasis, while survival upon infection is affected by loss of Yki in either the ISCs or ECs. My findings suggest that the Hpo pathway is a mediator of the regenerative response in the midgut. In the final part of the project, I have addressed possible mechanisms of Yki activation, with a view to gaining further insight into Yki function in the ECs. The data suggest a possible link between the generation of reactive oxygen species, JNK signalling and Yki activation. Several explanations could account for the requirement of Yki expression in the ECs. Yki expression itself might induce stress in the ECs, leading to upd expression and the regenerative response. Alternatively, the Hpo pathway might function as a stress sensor, triggering Upd release in response to noxious stimuli