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

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

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

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

The impact of multiple sclerosis on the identity of mothers in Italy

Purpose: This paper reports on one of the themes that emerged from the analysis of the study, regarding the perceived influence of multiple sclerosis (MS) on the identity of mothers in the socio-cultural context of Italy. Method: In-depth interviews were conducted with 16 women at various stages of MS, with follow up interviews with seven of the women. Phenomenology guided the methodology and the analysis was conducted using interpretative phenomenological analysis. Results: Through the research the value of motherhood to the women who participated emerged. The findings illustrated how many strove to maintain controlof their MS, which led to some making comparisons of themselves and other mothers and feeling different. Some women described how they adjusted their roles and found strength in being mothers but others spoke of their feelings of loss. Most women described living in the moment, appreciating the present and living each day as it came. Another significant experience was fear of stigma, both realized in the form of “pity” from others, and the perceived and actual associated stigma for their families. This contributed to why some women were reluctant to disclose their condition. The mothers who took part in this study differed in how they perceived their disabled identity. Conclusion: Although this study was conducted in the socio-cultural setting of Italy, the findings have implications for professionals working with disabled mothers and women with MS in Italy and beyond; including recognizing the value associated with fully identifying oneself as a mother, rather than solely focusing on doingmothering tasks. • Implications for Rehabilitation • Professionals need to be mindful of the value of motherhood for women with multiple sclerosis. • Professionals should support women who feel like they are battling with maintaining control of their multiple sclerosis, who may be adjusting their identity as mothers; recognizing that they may be influenced by the stage of their multiple sclerosis and whether they were diagnosed before or after having their children. • Women can have feelings of loss related to their ability to fully participate in their children’s lives and professionals should work with women to help them identify the value of their mothering role not only in physically participating in activities but also in being emotionally and physically present as a mother

Neurophysiological evidence that frontoparietal connectivity and GABA-A receptor changes underpin the antidepressant response to ketamine

This is the final version. Available on open access from Springer nature via the DOI in this recordData availability: The data underlying this article cannot be shared publicly as it was not part of the original ethics application to do so. The data will be shared on reasonable request to the corresponding author.Revealing the acute cortical pharmacodynamics of an antidepressant dose of ketamine in humans with depression is key to determining the specific mechanism(s) of action for alleviating symptoms. While the downstream effects are characterised by increases in plasticity and reductions in depressive symptoms—it is the acute response in the brain that triggers this cascade of events. Computational modelling of cortical interlaminar and cortico-cortical connectivity and receptor dynamics provide the opportunity to interrogate this question using human electroencephalography (EEG) data recorded during a ketamine infusion. Here, resting-state EEG was recorded in a group of 30 patients with major depressive disorder (MDD) at baseline and during a 0.44 mg/kg ketamine dose comprising a bolus and infusion. Fronto-parietal connectivity was assessed using dynamic causal modelling to fit a thalamocortical model to hierarchically connected nodes in the medial prefrontal cortex and superior parietal lobule. We found a significant increase in parietal-to-frontal AMPA-mediated connectivity and a significant decrease in the frontal GABA time constant. Both parameter changes were correlated across participants with the antidepressant response to ketamine. Changes to the NMDA receptor time constant and inhibitory intraneuronal input into superficial pyramidal cells did not survive correction for multiple comparisons and were not correlated with the antidepressant response. These results provide evidence that the antidepressant effects of ketamine may be mediated by acute fronto-parietal connectivity and GABA receptor dynamics. Furthermore, it supports the large body of literature suggesting the acute mechanism underlying ketamine’s antidepressant properties is related to GABA-A and AMPA receptors rather than NMDA receptor antagonism.Health Research Council of New ZealandWellcome Trus

A flexible procedure for multiple cadaveric organ procurement

Techniques have been developed which permit removal of the kidneys, liver, heart and other organs from the same donor without jeopardy to any of the individual grafts. The guiding principle is avoidance with all organs of warm ischemia. This is achieved by carefully timed and controlled infusion of cold solutions into anatomic regions, the limits of which are defined by preliminary dissection

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

Medical students' personal experience of high-stakes failure:case studies using interpretative phenomenological analysis

Abstract (provisional): Background Failing a high-stakes assessment at medical school is a major event for those who go through the experience. Students who fail at medical school may be more likely to struggle in professional practice, therefore helping individuals overcome problems and respond appropriately is important. There is little understanding about what factors influence how individuals experience failure or make sense of the failing experience in remediation. The aim of this study was to investigate the complexity surrounding the failure experience from the student’s perspective using interpretative phenomenological analysis (IPA). Methods The accounts of 3 medical students who had failed final re-sit exams, were subjected to in-depth analysis using IPA methodology. IPA was used to analyse each transcript case-by-case allowing the researcher to make sense of the participant’s subjective world. The analysis process allowed the complexity surrounding the failure to be highlighted, alongside a narrative describing how students made sense of the experience. Results The circumstances surrounding students as they approached assessment and experienced failure at finals were a complex interaction between academic problems, personal problems (specifically finance and relationships), strained relationships with friends, family or faculty, and various mental health problems. Each student experienced multi-dimensional issues, each with their own individual combination of problems, but experienced remediation as a one-dimensional intervention with focus only on improving performance in written exams. What these students needed to be included was help with clinical skills, plus social and emotional support. Fear of termination of the their course was a barrier to open communication with staff. Conclusions These students’ experience of failure was complex. The experience of remediation is influenced by the way in which students make sense of failing. Generic remediation programmes may fail to meet the needs of students for whom personal, social and mental health issues are a part of the picture