Successful bilateral lung transplantation after previous pneumonectomy

Objective: To present the feasibility of bilateral lung transplantation after previously performed pneumonectomy.Methods: A 32 years old women underwent right pneumonectomy for bronchiectasis-related destroyed lung. Eight months later, she developed a vascular post-pneumonectomy syndrome and underwent realigning of the mediastinum by an intrathoracic expander that was complicated by an adult respiratory distress syndrome of the left lung requiring mechanical ventilation, arterio-venous CO2 removal (Novalung) and finally bilateral lung transplantation. Via clamshell incision, the post-pneumonectomy cavity was dissected and the superior vena cava (SVC) and carina were exposed. The pulmonary vessel stumps were dissected intrapericardically after realization of a right-sided hemi-pericardectomy. Extracorporeal circulation was started after central cannulation of the aorta and the inferior vena cava. A right upper lobe sleeve resection of the donor lung was performed. The intermediate bronchus was then implanted in the dissected recipient carina after realization of a hilar release maneuver. The right pulmonary artery was clamped between SVC andthe ascending aorta followed by end -to-end anastomosis of the donor and recipient artery and left atrial cuffs, respectively. Satisfactory graft function allowed decanulation and standard transplantation of the left lung without extracorporeal circulation.Results: Bronchoscopy and trans-esophageal echocardiography demonstrated a patent airway and vascular anastomoses without stenosis. Follow-up revealed excellent gas exchanges, no airway complications and well-functioning grafts on both sides with right-sided ventilation and perfusion two months after transplantation of 37% and 22%, respectively.Conclusion: This is to our knowledge the first report of successful bilateral lung transplantation after previous pneumonectomy unrelated to transplantation.

Inappropriate antidiuretic hormone secretion: long-term successful urea treatment.

Hyponatremia is the main complication of inappropriate antidiuretic hormone secretion (SIADH), sometimes fatal. Treatment strategy depends on the cause and the severity of the hyponatremia. Recent studies have shown the efficacy of urea in treating acute hyponatremia secondary to SIADH, by inducing an osmotic water drive. We describe an infant with chronic hyponatremia secondary to SIADH in which the long-term oral treatment with urea was successful and well tolerated. The aim of this paper is to highlight the potential benefits of urea treatment in case of chronic hyponatremia secondary to SIADH. CONCLUSION: Chronic oral urea treatment in children with SIADH allows an easy and safe water and sodium control and may permit a decrease in fluid restriction in this situation.

Chaperones and proteases: cellular fold-controlling factors of proteins in neurodegenerative diseases and aging.

The formation of toxic protein aggregates is a common denominator to many neurodegenerative diseases and aging. Accumulation of toxic, possibly infectious protein aggregates induces a cascade of events, such as excessive inflammation, the production of reactive oxygen species, apoptosis and neuronal loss. A network of highly conserved molecular chaperones and of chaperone-related proteases controls the fold-quality of proteins in the cell. Most molecular chaperones can passively prevent protein aggregation by binding misfolding intermediates. Some molecular chaperones and chaperone-related proteases, such as the proteasome, can also hydrolyse ATP to forcefully convert stable harmful protein aggregates into harmless natively refoldable, or protease-degradable, polypeptides. Molecular chaperones and chaperone-related proteases thus control the delicate balance between natively folded functional proteins and aggregation-prone misfolded proteins, which may form during the lifetime and lead to cell death. Abundant data now point at the molecular chaperones and the proteases as major clearance mechanisms to remove toxic protein aggregates from cells, delaying the onset and the outcome of protein-misfolding diseases. Therapeutic approaches include treatments and drugs that can specifically induce and sustain a strong chaperone and protease activity in cells and tissues prone to toxic protein aggregations.

Neuronal inputs and outputs of aging and longevity.

An animal's survival strongly depends on its ability to maintain homeostasis in response to the changing quality of its external and internal environment. This is achieved through intracellular and intercellular communication within and among different tissues. One of the organ systems that plays a major role in this communication and the maintenance of homeostasis is the nervous system. Here we highlight different aspects of the neuronal inputs and outputs of pathways that affect aging and longevity. Accordingly, we discuss how sensory inputs influence homeostasis and lifespan through the modulation of different types of neuronal signals, which reflects the complexity of the environmental cues that affect physiology. We also describe feedback, compensatory, and feed-forward mechanisms in these longevity-modulating pathways that are necessary for homeostasis. Finally, we consider the temporal requirements for these neuronal processes and the potential role of natural genetic variation in shaping the neurobiology of aging.

Self-perception of aging and vulnerability to adverse outcomes at the age of 65-70 years.

OBJECTIVES. This study examines the relationship between self-perception of aging and vulnerability to adverse outcomes in adults aged 65-70 years using data from a cohort of 1,422 participants in Lausanne, Switzerland. METHODS: A positive or negative score of perception of aging was established using the Attitudes Toward Own Aging subscale including 5 items of the Philadelphia Geriatric Center Morale Scale. Falls, hospitalizations, and difficulties in basic and instrumental activities of daily living (ADL) collected in the first 3 years of follow-up were considered adverse outcomes. The relationship between perception and outcomes were evaluated using multiple logistic regression models adjusting for chronic medical conditions, depressive feelings, living arrangement, and socioeconomic characteristics. RESULTS: The strongest associations of self-perception of aging with outcomes were observed for basic and instrumental ADL. Associations with falls and hospitalizations were not constant but could be explained by health characteristics. CONCLUSIONS: A negative self-perception of aging is an indicator of risk for future disability in ADL. Factors such as a low-economic status, living alone, multiple chronic medical conditions, and depressive feelings contribute to a negative self-perception of aging but do not explain the relationship with incident activities of daily living disability.

No major impact of skin aging on the response of skin blood flow to a submaximal local thermal stimulus.

OBJECTIVE: This study was undertaken to investigate how aging affects dermal microvascular reactivity in skin areas differentially exposed to sunlight, and therefore to different degrees of photoaging. METHODS: We assessed, in young (18-30 years, n = 13) and aged males (≥60 years, n = 13), the thigh, forearm, and forehead's skin vasodilatory response to local heating (LTH) with a LDI. In each subject and at each location, local Tskin was brought from 34°C (baseline) to 39 or 41°C for 30 minutes, to effect submaximal vasodilation, with maximal vasodilation then elicited by further heating to 44°C. RESULTS: The CVCs evaluated at baseline and after maximal vasodilation (CVCmax ) were higher in the forehead than in the two other anatomical locations. On all locations, CVCmax decreased with age but less markedly in the forehead compared to the two other locations. When expressed in % of CVCmax , the plateau increase of CVCs in response to submaximal temperatures (39 and 41°C) did not vary with age, and minimally so with location. CONCLUSION: Skin aging, whether intrinsic or combined with photoaging, reduces the maximal vasodilatory capacity of the dermal microcirculation, but not its reactivity to local heating.

Successful migration of three tracers without identification of sentinel nodes during intraoperative lymphatic mapping for non-small cell lung cancer.

Prospective comparative evaluation of patent V blue, fluorescein and (99m)TC-nanocolloids for intraoperative sentinel lymph node (SLN) mapping during surgery for non-small cell lung cancer (NSCLC). Ten patients with peripherally localised clinical stage I NSCLC underwent thoracotomy and peritumoral subpleural injection of 2 ml of patent V blue dye, 1 ml of 10% fluorescein and 1ml of (99m)Tc-nanocolloids (0.4 mCi). The migration and spatial distribution pattern of the tracers was assessed by direct visualisation (patent V blue), visualisation of fluorescence signalling by a lamp of Wood (fluorescein) and radioactivity counting with a hand held gamma-probe ((99m)Tc-nanocolloids). Lymph nodes at interlobar (ATS 11), hilar (ATS 10) and mediastinal (right ATS 2,4,7; left ATS 5,6,7) levels were systematically assessed every 10 min up to 60 min after injection, followed by lobectomy and formal lymph node dissection. Successful migration from the peritumoral area to the mediastinum was observed for all three tracers up to 60 min after injection. The interlobar lympho-fatty tissue (station ATS 11) revealed an early and preferential accumulation of all three tracers for all tumours assessed and irrespective of the tumour localisation. However, no preferential accumulation in one or two distinct lymph nodes was observed up to 60 min after injection for all three tracers assessed. Intraoperative SLN mapping revealed successful migration of the tracers from the site of peritumoral injection to the mediastinum, but in a diffuse pattern without preferential accumulation in sentinel lymph nodes.

Generative FDG-PET and MRI model of aging and disease progression in Alzheimer's disease.

The failure of current strategies to provide an explanation for controversial findings on the pattern of pathophysiological changes in Alzheimer's Disease (AD) motivates the necessity to develop new integrative approaches based on multi-modal neuroimaging data that captures various aspects of disease pathology. Previous studies using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (sMRI) report controversial results about time-line, spatial extent and magnitude of glucose hypometabolism and atrophy in AD that depend on clinical and demographic characteristics of the studied populations. Here, we provide and validate at a group level a generative anatomical model of glucose hypo-metabolism and atrophy progression in AD based on FDG-PET and sMRI data of 80 patients and 79 healthy controls to describe expected age and symptom severity related changes in AD relative to a baseline provided by healthy aging. We demonstrate a high level of anatomical accuracy for both modalities yielding strongly age- and symptom-severity- dependant glucose hypometabolism in temporal, parietal and precuneal regions and a more extensive network of atrophy in hippocampal, temporal, parietal, occipital and posterior caudate regions. The model suggests greater and more consistent changes in FDG-PET compared to sMRI at earlier and the inversion of this pattern at more advanced AD stages. Our model describes, integrates and predicts characteristic patterns of AD related pathology, uncontaminated by normal age effects, derived from multi-modal data. It further provides an integrative explanation for findings suggesting a dissociation between early- and late-onset AD. The generative model offers a basis for further development of individualized biomarkers allowing accurate early diagnosis and treatment evaluation.

Alterations in neurofilament protein immunoreactivity in human hippocampal neurons related to normal aging and Alzheimer's disease.

The distribution of immunoreactivity for the neurofilament triplet class of intermediate filament proteins was examined in the hippocampus of young, adult and elderly control cases and compared to that of Alzheimer's disease cases. In a similar fashion to non-human mammalian species, pyramidal neurons in the CA1 region showed a very low degree of neurofilament triplet immunoreactivity in the three younger control cases examined. However, in the other control cases of 49 years of age and older, many CA1 pyramidal neurons showed elevated neurofilament immunoreactivity. In the Alzheimer's disease cases, most of the surviving CA1 neurons showed intense labeling for the neurofilament triplet proteins, with many of these neurons giving off abnormal "sprouting" processes. Double labeling demonstrated that many of these neurons contained tangle-like or granular material that was immunoreactive for abnormal forms of tau and stained with thioflavine S, indicating that these neurons are in a transitional degenerative stage. An antibody to phosphorylated neurofilament proteins labeled a subset of neurofibrillary tangles in the Alzheimer's disease cases. However, following formic acid pre-treatment, the number of neurofibrillary tangles showing phosphorylated neurofilament protein immunoreactivity increased, with double labeling confirming that all of the tau-immunoreactive neurofibrillary tangles were also immunoreactive for phosphorylated neurofilament proteins. Immunoblotting demonstrated that there was a proportionately greater amount of the neurofilament triplet subunit proteins in hippocampal tissue from Alzheimer's disease cases as compared to controls. These results indicate that there are changes in the cytoskeleton of CA1 neurons associated with age which are likely to involve an increase in the level of neurofilament proteins and may be a predisposing factor contributing towards their high degree of vulnerability in degenerative conditions such as Alzheimer's disease. The cellular factors affecting hippocampal neurons during aging may be potentiated in Alzheimer's disease to result in even higher levels of intracellular neurofilament proteins and the progressive alterations of neurofilaments and other cytoskeletal proteins that finally results in neurofibrillary tangle formation and cellular degeneration.

Aging preferentially affects molecular pathways implicated in development and disease of myelinating glial cells

The central and peripheral nervous systems are involved in multiple age-dependent neurological deficits that are often attributed to alterations in function of myelinating glial cells. However, the molecular events that underlie the age-related decline of glial cell function are unknown. We used Schwann cells as a model to study biological processes affected in glial cells by aging. We comprehensively profiled gene expression of the Schwann cellrich mouse sciatic nerve throughout life, from day of birth until senescence (840 days of age). We combined the aging data with the microarray transcriptional data obtained using nerves isolated from Schwann cell-specific neuropathy-inducing mutants MPZCre/+/Lpin1fE2−3/fE2−3 , MPZCre/+/ScapfE1/fE1 and Pmp22-null mice. The majority of age related transcripts were also affected in the analyzed mouse models of neuropathy (54.4%) and in development (59.5%) indicating a high level of overlapping in implicated molecular pathways. We observed that compared to peripheral nerve development, dynamically changing expression profiles in aging have opposite (anticorrelated) orientation while they copy the orientation of transcriptional changes observed in analyzed neuropathy models. Subsequent clustering and biological annotation of dynamically changing transcripts revealed that the processes most significantly deregulated in aging include inflammatory/immune response and lipid biosynthesis/metabolism. Importantly, the changes in these pathways were also observed in myelinated oligodendrocyte-rich optic nerves of aged mice, albeit with lower magnitude. This observation suggests that similar biological processes are affected in aging glial cells in central and peripheral nervous systems, however with different dynamics. Our data, which provide the first comprehensive comparison of molecular changes in glial cells in three distinct biological conditions comprising development, aging and disease, provide not only a new inside into the molecular alterations underlying neural system aging but also identify target pathways for potential therapeutic approaches to prevent or delay complications associated with age-related and inherited forms of neuropathies. *Current address: Department of Physiology, UCSF, San Francisco, CA, USA.

Interhemispheric coupling between the posterior sylvian regions impacts successful auditory temporal order judgment.

Accurate perception of the temporal order of sensory events is a prerequisite in numerous functions ranging from language comprehension to motor coordination. We investigated the spatio-temporal brain dynamics of auditory temporal order judgment (aTOJ) using electrical neuroimaging analyses of auditory evoked potentials (AEPs) recorded while participants completed a near-threshold task requiring spatial discrimination of left-right and right-left sound sequences. AEPs to sound pairs modulated topographically as a function of aTOJ accuracy over the 39-77ms post-stimulus period, indicating the engagement of distinct configurations of brain networks during early auditory processing stages. Source estimations revealed that accurate and inaccurate performance were linked to bilateral posterior sylvian regions activity (PSR). However, activity within left, but not right, PSR predicted behavioral performance suggesting that left PSR activity during early encoding phases of pairs of auditory spatial stimuli appears critical for the perception of their order of occurrence. Correlation analyses of source estimations further revealed that activity between left and right PSR was significantly correlated in the inaccurate but not accurate condition, indicating that aTOJ accuracy depends on the functional decoupling between homotopic PSR areas. These results support a model of temporal order processing wherein behaviorally relevant temporal information--i.e. a temporal 'stamp'--is extracted within the early stages of cortical processes within left PSR but critically modulated by inputs from right PSR. We discuss our results with regard to current models of temporal of temporal order processing, namely gating and latency mechanisms.

A model for organ donation in switzerland, the latin organ donation programme (lodp); an ongoing successful regional initiative

Background: The 1st Swiss federal Transplant Law was finally enforced in July 2007 with the obligation to promote quality and efficiency in transplant procedures. The LODP was created to develop organ and tissue donation in the Latin area of Switzerland covering seventeen hospitals (29% of the population).Methods: Each of the partner hospitals designated at least one Local Donor Coordinator (LDC), member of the Intensive Care team, trained in the organ donation (OD) process. The principal tasks of the LDC's are the introduction of OD procedures, organisation of educational sessions for hospital staff and execution of the Donor Action programme. The LODP has been operational since July 2009, when training of the LDC's was completed, the web-site and hotline activated and the attendance of Transplant Procurement Coordinators (TPC) during the OD process organised.Results: National and regional guidelines are accessible on the LODP website. The Hospital Attitude Survey obtained a 57% return rate. Many of the staff requested training and sessions are now running in the partner hospitals. The Medical Record Revue revealed an increase in the conversion rate from 3.5% to 4.5%. During the 5 years before creation of LODP the average annual number of utilised donors was 31, an increase of 70%, has since been observed.Conclusion: This clear progression in utilised donors in the past two years can be attributed to the fact that partner hospitals benefit from the various support given (hotline, website and from TPC's). Despite the increase in OD within the LODP the Swiss donation rates remain low, on average 11.9 donors per million population. This successful model should be applied throughout Switzerland, but the crucial point is to obtain financial support.

Long live the queen: studying aging in social insects

Aging is a fascinating, albeit controversial, chapter in biology. Few other subjects have elicited more than a century of ever-increasing scientific interest. In this review, we discuss studies on aging in social insects, a group of species that includes ants and termites, as well as certain bee and wasp species. One striking feature of social insects is the lifespan of queens (reproductive females), which can reach nearly 30 years in some ant species. This is over 100 times the average lifespan of solitary insects. Moreover, there is a tremendous variation in lifespan among castes, with queens living up to 500 times longer than males and 10 times longer than workers (non-reproductive individuals). This lifespan polymorphism has allowed researchers to test the evolutionary theory of aging and Y more recently Y to investigate the proximate causes of aging. The originality of these studies lies in their use of naturally evolved systems to address questions related to aging and lifespan determination that cannot be answered using the conventional model organisms.