Multiple right-sided pulmonary nodules: metastatic cancer or resectable early stage tumor?

The aim of this paper is to focus attention on complex cases of lung disease that may benefit from being managed outside formal guidelines. A 52 year-old man who had previously undergone a laryngectomy for squamous cell carcinoma, presented with a 1.2 cm nodule in the right upper pulmonary lobe. Three months later a new CT scan found that the nodule had slightly increased in size and also detected two new smaller nodules in the middle lobe. A PET/CT scan showed metabolic hyperactivity of all nodules. Since needle aspiration of the upper one revealed malignant cells, the patient was considered to be suffering from metastatic cancer and started on chemotherapy. At follow-up both CT and PET scans found a significant reduction in volume and activity of the lower nodules but no change in the upper one. At diagnostic thoracoscopy, histology demonstrated that the upper nodule was an adenocarcinoma while the lower ones were inflammatory. An upper lobectomy and systematic nodal dissection were therefore performed. Histology established a diagnosis of upper pulmonary adenocarcinoma and sarcoidosis. Our report suggests that in complicated oncologic cases in which non-invasive diagnostic tools yield incongruous results surgery should be considered without delay

The critical role of logarithmic transformation in Nernstian equilibrium potential calculations

The membrane potential, arising from uneven distribution of ions across cell membranes containing selectively permeable ion channels, is of fundamental importance to cell signaling. The necessity of maintaining the membrane potential may be appreciated by expressing Ohm’s law as current = voltage/resistance and recognizing that no current flows when voltage = 0, i.e., transmembrane voltage gradients, created by uneven transmembrane ion concentrations, are an absolute requirement for the generation of currents that precipitate the action and synaptic potentials that consume >80% of the brain’s energy budget and underlie the electrical activity that defines brain function. The concept of the equilibrium potential is vital to understanding the origins of the membrane potential. The equilibrium potential defines a potential at which there is no net transmembrane ion flux, where the work created by the concentration gradient is balanced by the transmembrane voltage difference, and derives from a relationship describing the work done by the diffusion of ions down a concentration gradient. The Nernst equation predicts the equilibrium potential and, as such, is fundamental to understanding the interplay between transmembrane ion concentrations and equilibrium potentials. Logarithmic transformation of the ratio of internal and external ion concentrations lies at the heart of the Nernst equation, but most undergraduate neuroscience students have little understanding of the logarithmic function. To compound this, no current undergraduate neuroscience textbooks describe the effect of logarithmic transformation in appreciable detail, leaving the majority of students with little insight into how ion concentrations determine, or how ion perturbations alter, the membrane potential

Chemical pneumonitis and subsequent reactive airways dysfunction syndrome after a single exposure to a household product: a case report

<p>Abstract</p> <p>Introduction</p> <p>Household products are usually safe to use. Adverse events arising from their use are mostly reported in patients with pre-existing atopy or pulmonary problems and usually only after a prolonged exposure to such products. We report the case of a patient with no prior problems who developed significant side effects from a single exposure to a domestic product.</p> <p>Case presentation</p> <p>A 43-year-old Caucasian American man, previously in good health, used a domestic aerosol product called 'Stand N' Seal "Spray-On" Grout Sealer' in an enclosed room in his house. The product contained n-butyl acetate (<5%), propane (10%), isobutane (<5%), C8-C9 petroleum hydrocarbon solvent (80%), a fluoropolymer resin and a solvent. Within a few hours of exposure to the sealant, he developed rapidly progressive shortness of breath and a severe non-productive cough. By the time he reached the emergency room he was severely hypoxic. A diagnosis of chemical pneumonitis was made based on the clinical scenario and the diffuse infiltrates on the computer tomography scan. With supportive therapy, his condition improved and he was discharged from the hospital. However, he continued to have symptoms of intermittent cough and shortness of breath in response to strong odours, fumes, cold air and exertion even after his chest radiograph had normalized. Three months later, bronchial hyper-responsiveness was documented by a methacholine inhalation test and a diagnosis of reactive airways dysfunction syndrome was made. The patient was started on high-dose inhaled steroids and his symptoms improved. The mechanism of toxicity and determination of the exact agent responsible is still under investigation.</p> <p>Conclusion</p> <p>A household product may still prove unsafe to use even after it has gone through vigorous testing and approval processes. Even healthy individuals are susceptible to adverse outcomes after a brief exposure. Extra precautions should be taken when using any chemical product at home.</p

Multidisciplinary team meetings and their impact on workflow in radiology and pathology departments

<p>Abstract</p> <p>Background</p> <p>The development of multidisciplinary team meetings (MDTMs) for radiology and pathology is a burgeoning area that increasingly impacts on work processes in both of these departments. The aim of this study was to examine work processes and quantify the time demands on radiologists and pathologists associated with MDTM practices at a large teaching hospital. The observations reported in this paper reflect a general trend affecting hospitals and our conclusions will have relevance for others implementing clinical practice guidelines.</p> <p>Methods</p> <p>For one month, all work related to clinical meetings between pathology and radiology with clinical staff was documented and later analysed.</p> <p>Results</p> <p>The number of meetings to which pathology and radiology contribute at a large university teaching hospital, ranges from two to eight per day, excluding grand rounds, and amounts to approximately 50 meetings per month for each department. For one month, over 300 h were spent by pathologists and radiologists on 81 meetings, where almost 1000 patients were discussed. For each meeting hour, there were, on average, 2.4 pathology hours and 2 radiology hours spent in preparation. Two to three meetings per week are conducted over a teleconferencing link. Average meeting time is 1 h. Preparation time per meeting ranges from 0.3 to 6 h for pathology, and 0.5 to 4 for radiology. The review process in preparation for meetings improves internal quality standards. Materials produced externally (for example imaging) can amount to almost 50% of the material to be reviewed on a single patient. The number of meetings per month has increased by 50% over the past two years. Further increase is expected in both the numbers and duration of meetings when scheduling issues are resolved. A changing trend in the management of referred patients with the development of MDTMs and the introduction of teleconferencing was noted.</p> <p>Conclusion</p> <p>Difficulties are being experienced by pathology and radiology departments participating fully in several multidisciplinary teams. Time spent at meetings, and in preparation for MDTMs is significant. Issues of timing and the coordination of materials to be reviewed are sometimes irreconcilable. The exchange of patient materials with outside institutions is a cause for concern when full data are not made available in a timely fashion. The process of preparation for meetings is having a positive influence on quality, but more resources are needed in pathology and radiology to realise the full benefits of multidisciplinary team working.</p

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive

Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson’s disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model

Susceptibility of Human Lymphoid Tissue Cultured ex vivo to Xenotropic Murine Leukemia Virus-Related Virus (XMRV) Infection

BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV) was generated after a recombination event between two endogenous murine leukemia viruses during the production of a prostate cancer cell line. Although the associations of the XMRV infection with human diseases appear unlikely, the XMRV is a retrovirus of undefined pathogenic potential, able to replicate in human cells in vitro. Since recent studies using animal models for infection have yielded conflicting results, we set out an ex vivo model for XMRV infection of human tonsillar tissue to determine whether XMRV produced by 22Rv1 cells is able to replicate in human lymphoid organs. Tonsil blocks were infected and infection kinetics and its pathogenic effects were monitored RESULTS: XMRV, though restricted by APOBEC, enters and integrates into the tissue cells. The infection did not result in changes of T or B-cells, immune activation, nor inflammatory chemokines. Infectious viruses could be recovered from supernatants of infected tonsils by reinfecting DERSE XMRV indicator cell line, although these supernatants could not establish a new infection in fresh tonsil culture, indicating that in our model, the viral replication is controlled by innate antiviral restriction factors. CONCLUSIONS: Overall, the replication-competent retrovirus XMRV, present in a high number of laboratories, is able to infect human lymphoid tissue and produce infectious viruses, even though they were unable to establish a new infection in fresh tonsillar tissue. Hereby, laboratories working with cell lines producing XMRV should have knowledge and understanding of the potential biological biohazardous risks of this virus

Mitochondrial phylogeography of baboons (Papio spp.) – Indication for introgressive hybridization?

<p>Abstract</p> <p>Background</p> <p>Baboons of the genus <it>Papio </it>are distributed over wide ranges of Africa and even colonized parts of the Arabian Peninsula. Traditionally, five phenotypically distinct species are recognized, but recent molecular studies were not able to resolve their phylogenetic relationships. Moreover, these studies revealed para- and polyphyletic (hereafter paraphyletic) mitochondrial clades for baboons from eastern Africa, and it was hypothesized that introgressive hybridization might have contributed substantially to their evolutionary history. To further elucidate the phylogenetic relationships among baboons, we extended earlier studies by analysing the complete mitochondrial cytochrome <it>b </it>gene and the 'Brown region' from 67 specimens collected at 53 sites, which represent all species and which cover most of the baboons' range.</p> <p>Results</p> <p>Based on phylogenetic tree reconstructions seven well supported major haplogroups were detected, which reflect geographic populations and discordance between mitochondrial phylogeny and baboon morphology. Our divergence age estimates indicate an initial separation into southern and northern baboon clades 2.09 (1.54–2.71) million years ago (mya). We found deep divergences between haplogroups within several species (~2 mya, northern and southern yellow baboons, western and eastern olive baboons and northern and southern chacma baboons), but also recent divergence ages among species (< 0.7 mya, yellow, olive and hamadryas baboons in eastern Africa).</p> <p>Conclusion</p> <p>Our study confirms earlier findings for eastern Africa, but shows that baboon species from other parts of the continent are also mitochondrially paraphyletic. The phylogenetic patterns suggest a complex evolutionary history with multiple phases of isolation and reconnection of populations. Most likely all these biogeographic events were triggered by multiple cycles of expansion and retreat of savannah biomes during Pleistocene glacial and inter-glacial periods. During contact phases of populations reticulate events (i.e. introgressive hybridization) were highly likely, similar to ongoing hybridization, which is observed between East African baboon populations. Defining the extent of the introgressive hybridization will require further molecular studies that incorporate additional sampling sites and nuclear loci.</p

Astrocytic Ca2+ Waves Guide CNS Growth Cones to Remote Regions of Neuronal Activity

Activity plays a critical role in network formation during developmental, experience-dependent, and injury related remodeling. Here we report a mechanism by which axon trajectory can be altered in response to remote neuronal activity. Using photoconductive stimulation to trigger high frequency action potentials in rat hippocampal neurons in vitro, we find that activity functions as an attractive cue for growth cones in the local environment. The underlying guidance mechanism involves astrocyte Ca2+ waves, as the connexin-43 antagonist carbenoxolone abolishes the attraction when activity is initiated at a distance greater than 120 µm. The asymmetric growth cone filopodia extension that precedes turning can be blocked with CNQX (10 µM), but not with the ATP and adenosine receptor antagonists suramin (100 µM) and alloxazine (4 µM), suggesting non-NMDA glutamate receptors on the growth cone mediate the interaction with astrocytes. These results define a potential long-range signalling pathway for activity-dependent axon guidance in which growth cones turn towards directional, temporally coordinated astrocyte Ca2+ waves that are triggered by neuronal activity. To assess the viability of the guidance effect in an injury paradigm, we performed the assay in the presence of conditioned media from lipopolysaccharide (LPS) activated purified microglial cultures, as well as directly activating the glia present in our co-cultures. Growth cone attraction was not inhibited under these conditions, suggesting this mechanism could be used to guide regeneration following axonal injury