Predictive value and limitations of animal models for human transplantation: do we need more models for facial transplantation?

Animal models have traditionally provided the basis for preliminary investigation of new techniques prior to trials taking place in human subjects. The timing of when to proceed with human trials is difficult, as the accuracy of preclinical models can only be determined with hindsight. This review outlines the progression from transplantation in animal models to man. Now that many transplant procedures are well established, it is possible to assess the predictive value and limitations of animal models. These results are of great importance in the current debate about composite tissue allotransplantation (CTA) and in particular facial transplantation. This progression of CTA from animal models to man is outlined and compared with early renal, cardiac, and liver transplants. There is some evidence to suggest that animal models may have been misleading in CTA and that this has effectively delayed the transition to humans. The role for animal models in facial transplantation, which is currently making the step to clinical trials, is discussed.     

PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.     

BUILDING THE FOUNDATION OF EXCELLENCE IN HEART FAILURE NURSING

This column contains the presidential address presented during the Third Annual Meeting of the American Association of Heart Failure Nurses on June 28, 2007, in San Diego, California, titled "Building the Foundation of Excellence in Heart Failure Nursing."     

Lymphocytes capable of mediating delayed-type hypersensitivity reactions accumulate within sponge matrix allografts

The rejection of sponge matrix allografts across H-2 barriers has generally been found to contain specifically sensitized cytotoxic T cells to donor alloantigen. There is one exception: sponge matrix allografts that differ only with respect to class II alloantigens do not contain specifically sensitized cytotoxic T cells. We therefore investigated the capacity of infiltrating cells removed from sponge matrix allografts to generate delayed hypersensitivity reactions after exposure to fresh alloantigen in a footpad assay. Cells infiltrating class I and II allografts were equally capable of eliciting delayed footpad reactions when injected with specific donor alloantigen into the footpads of naive responder strain mice. Allosensitized T-lymphocyte clones of helper or cytotoxic type were also capable of initiating delayed-type hypersensitivity (DTH) reactions in vivo. We conclude that rejecting allografts across class I or II alloantigenic barriers are infiltrated by cells capable of effecting DTH reactions, in addition to their capacity to exert specific helper or specific cytotoxic reactions. The results also support that both helper and cytotoxic T cells can participate in allospecific DTH reactions.     

Bipolar disorder in children and adolescents: obstacles to early diagnosis and future directions

Aim: This article reviews research centred around juvenile bipolar disorder with particular reference to diagnostic difficulties. Putative deficits are scrutinized with respect to trait likelihood and the roles of neuropsychology and neuroimaging in enhancing our understanding of juvenile bipolar disorder are discussed. Methods: Search terms including childhood, adolescent, youth and juvenile combined with the terms ‘bipolar disorder’, mania, depression and hypomania were used to identify relevant studies in MEDLINE and PsychLit. Results: Over recent years research into this relatively new disorder has increased phenomenally. Key issues within the field include diagnostic specificity, the heritability of the disorder, the impact of comorbidity and the implications of neuropsychological and neuroimaging findings. Conclusion: Despite concerning controversies in literature the diagnosis of bipolar disorder in children and adolescents as compared with adults, promising future research directions include better neurological characterization of the disorder through the application of findings from clinical populations, neuropsychological and neuroimaging research.     

The effect of perioperative beta-blockade on the pulmonary function of patients undergoing major arterial surgery.

INTRODUCTION: Concern about the potential detrimental side-effects of beta-blockade on pulmonary function often dissuades against their perioperative use in patients undergoing major arterial surgery (especially in those with chronic obstructive pulmonary disease (COPD)). In this study we aimed to establish prospectively the clinical relevance of these concerns. METHODS: After ethics committee approval and individual informed consent, the pulmonary function of twenty patients (mean age 68.7 years (range 43-82), 11 males) scheduled to undergo non-emergency major vascular surgery was studied by recording symptoms and spirometry before and after institution of effective beta-blockade. Fifteen patients (75%) had significant smoking histories (mean pack years/patient=50), while 12 (60%) had COPD. RESULTS: All patients tolerated effective beta-blockade satisfactorily without developing either subjective deterioration in symptoms or significant change on spirometry. The mean change in FEV1 following adequate beta-blockade was 0.05+/-0.24 liters (95% CI -0.06 to +1.61), p=0.35, giving a mean percentage change of 3.18%+/-11.66 (95% CI -2.26 to 8.62). CONCLUSIONS: Previously held concerns about worsening pulmonary function through the short-term use of beta-blockers should not dissuade their perioperative usage in patients with peripheral vascular disease. Furthermore, the accuracy of pulmonary function tests in preoperative assessment and risk stratification also appears unaffected by this therapy.     

What should nurse teachers be doing? A preliminary study

There is little doubt that the role of the nurse teacher is complex and multifaceted in nature. The apparently conflicting demands of NHS trusts and education in the United Kingdom, at the time of integration of nurse education into the higher education sector, further complicates the role. This recognition underlines the need to capture and measure key aspects of nurse teacher function in order to maximize educational gain. Using a comprehensive literature review, focus group discussions and a small number of individual semi-structured interviews, this preliminary study explored the issue of teacher workload, from the perspective of the principal stakeholders in nurse and higher education. Competing research and clinical practice objectives for nurse teachers are identified against a background of changing health care provision, reduced availability of placements and an increased need for evidence-based practice.     

The right approach to carcinoma of the cardia and lower oesophagus.

Successful surgical palliation for carcinoma of the cardia and lower oesophagus is often compromised by anastomotic failure or local recurrence. These complications follow technical difficulty in achieving adequate resection and a safe anastomosis through inappropriate surgical exposure, often via the left chest. A technique of oesophagogastrectomy is described employing a simultaneous right abdominothoracic approach without division of either costal margin or diaphragm. Synchronous laparotomy and thoractomy facilitates both resection and anastomosis, and obviates the necessity to turn the patient over and redrape halfway through the operation. Closure of the distal stomach and the gastro-oesophageal anastomosis are performed using staplers. No anastomotic leaks were detected in the 15 patients described.     

Placement of anterior cervical instrumentation without intraoperative radiography.

Adequate fixation with several commonly used anterior cervical plate systems requires that the screws penetrate both the anterior and posterior cortices of the vertebral bodies. This report emphasizes the shortcomings of plain film and fluoroscopic examinations in confirming screw position through the posterior vertebral cortex in three patients with lower cervical trauma or tumor. These cases and radiographs of isolated vertebrae from the cervicothoracic region demonstrate the inadequacy of plain film/fluoroscopy for determination of the position of anterior cervical plate screws in relation to the posterior cortex. Only axial images such as those obtained with computed tomography are able to show the exact relationship of the screws to the posterior cortical curvature in C7 and T1.