Vitamin B12 deficiency-induced neuropathy secondary to prolonged recreational use of nitrous oxide

A 24-year-old female, otherwise healthy, presented to the Emergency Department (ED) with difficulty walking and bilateral leg pain. The patient was a recreational nitrous oxide (NO₂) user, also known as “whippets” or simply nitrous. Neurologic examination demonstrated an unsteady gait and positive Romberg sign along with normal deep tendon reflexes and normal muscle strength in upper and lower extremities. Laboratory results demonstrated macrocytic erythropoiesis, reduced B₁₂, elevated homocysteine, and elevated methylmalonic acid. Outpatient MRI later demonstrated degeneration of the posterior spinal column. The patient was empirically treated in the ED with intramuscular B₁₂ and admitted to the evaluation unit for pain control and Physical Therapy (PT) evaluation.Emergency Medicine (EM) physicians should be aware of this condition because NO₂ is used both recreationally and in medicine. With the popularity of recreational nitrous oxide, many emergency patients have experience with this drug. As in our case report, the toxic effects can be profound and mimic other emergent conditions like stroke. Emergency physicians should have a higher index of suspicion for the toxic effects of this common drug. Elderly, vegetarians and patients with Irritable Bowel Disease are at higher risk and may even experience toxicity from nitrous oxide used therapeutically during routine anesthesia.     

Targeted sequencing using a 47 gene multiple myeloma mutation panel (M3P) in ‐17p high risk disease

We constructed a multiple myeloma (MM)‐specific gene panel for targeted sequencing and investigated 72 untreated high‐risk (del17p) MM patients. Mutations were identified in 78% of the patients. While the majority of studied genes were mutated at similar frequency to published literature, the prevalence of TP53 mutation was increased (28%) and no mutations were found in FAM46C. This study provides a comprehensive insight into the mutational landscape of del17p high‐risk MM. Additionally, our work demonstrates the practical use of a customized sequencing panel, as an easy, cheap and fast approach to characterize the mutational profile of MM.     

Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition

Dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32), encoded by PPP1R1B, is a pivotal integrator of information in dopaminoceptive neurons, regulating the response to neuroleptics, psychotomimetics, and drugs of abuse, and affecting striatal function and plasticity. Despite extensive preclinical work, there are almost no data on DARPP-32 function in humans. Here, we identify, through resequencing in 298 chromosomes, a frequent PPP1R1B haplotype predicting mRNA expression of PPP1R1B isoforms in postmortem human brain. This haplotype was associated with enhanced performance on several cognitive tests that depend on frontostriatal function. Multimodal imaging of healthy subjects revealed an impact of the haplotype on neostriatal volume, activation, and the functional connectivity of the prefrontal cortex. The haplotype was associated with the risk for schizophrenia in 1 family-based association analysis. Our convergent results identify a prefrontal-neostriatal system affected by variation in PPP1R1B and suggest that DARPP-32 plays a pivotal role in cognitive function and possibly in the pathogenesis of schizophrenia.     

A qualitative study of the experiences of people who identify themselves as having adjusted positively to a visible difference

Individual and group interviews explored experiences of positive adjustment among 12 people with a range of visible differences. Thematic analysis identified four main themes: importance of appearance; personal growth; relationships with others; and coping (factors in the coping theme considered to be paramount to positive adjustment were inner strength and positivity, active coping techniques, downward social comparisons, taking things day-by-day, spirituality and humour). The findings provide insight into behaviours and personal outlooks that may contribute to adaptive coping and have implications for future research and interventions aimed at those who exhibit poor adjustment to visible difference. The article reflects on the use of both individual and group interviews for research in this field.     

An association between reduced interhemispheric EEG coherence in the temporal lobe and genetic risk for schizophrenia

Previous studies have suggested that schizophrenic patients show resting changes such as frequency-slowing and decreased coherence in the frontal and temporal area. We sought to determine whether these findings are also found in clinically unaffected siblings of schizophrenics and estimate heritability by calculating relative risk. We investigated two independent data sets: (1) from the NIMH St. Elisabeth's campus (59 schizophrenics, 76 unaffected siblings and 32 unrelated normal controls) and (2) from the NIH-campus (Bethesda) (59 schizophrenics, 90 unaffected siblings and 26 unrelated normal controls). We computed power spectra and coherence on the first data set and then tried to replicate the results on the second data set. Power spectrum analysis suggested that schizophrenics are cortically hypoactivated, whereas in unaffected siblings, a tendency for hyperactivation was found. In contrast, spectral coherences (0.5-5Hz) were reduced in both data sets in the temporal lobe areas in schizophrenics and in their unaffected siblings. Changes were most pronounced for the interhemispheric coherence linking both posterior temporal lobe areas. Relative risk calculations (lambda(S)) ranged between 3.7 and 9.8, depending on phenotype definition. Thus, while power spectrum EEG abnormalities may be state-dependent, reduced coherence as a possible measure of neuronal synchronization is familial and potentially a heritable trait related to genetic risk for schizophrenia.     

Neural correlates of the emergence of consciousness of thirst

Thirst was induced by rapid i.v. infusion of hypertonic saline (0.51 M at 13.4 ml/min). Ten humans were neuroimaged by positron-emission tomography (PET) and four by functional MRI (fMRI). PET images were made 25 min after beginning infusion, when the sensation of thirst began to enter the stream of consciousness. The fMRI images were made when the maximum rate of increase of thirst occurred. The PET results showed regional cerebral blood flow changes similar to those delineated when thirst was maximal. These loci involved the phylogenetically ancient areas of the brain. fMRI showed activation in the anterior wall of the third ventricle, an area that is key in the genesis of thirst but is not an area revealed by PET imaging. Thus, this region plays as major a role in thirst for humans as for animals. Strong activations in the brain with fMRI included the anterior cingulate, parahippocampal gyrus, inferior and middle frontal gyri, insula, and cerebellum. When the subjects drank water to satiation, thirst declined immediately to baseline. A precipitate decline in intensity of activation signal occurred in the anterior cingulate area (Brodmann area 32) putatively related to consciousness of thirst. The intensity of activation in the anterior wall of the third ventricle was essentially unchanged, which is consistent with the fact that a significant time (15-20 min) would be needed before plasma Na concentration changed as a result of water absorption from the gut.     

Comparison of human metapneumovirus and respiratory syncytial virus in children admitted to a paediatric intensive care unit

Aim: To describe the clinical presentation and course of children admitted to the paediatric intensive care unit (PICU) with human metapneumovirus (hMPV) infection, and compare them with children admitted to the PICU with respiratory syncytial virus (RSV) infection. Methods: hMPV was identified by immunofluorescence in 22 children admitted to the PICU over a 16‐month period. The medical records of these children were reviewed retrospectively, and their clinical and laboratory data were compared with 66 children admitted to the PICU with positive tests for RSV over the same period. Results: Children admitted to the PICU with hMPV were significantly older than children with RSV (P= 0.003). Children with hMPV presented more commonly with pneumonia or pneumonitis (29% vs. 16%), and less commonly with bronchiolitis (43% vs. 68%) than RSV (P= 0.13). Invasive ventilation was required in 10 patients (48%) with hMPV, and non‐invasive ventilation was required in a further 5 (28%), similar to patients with RSV. Children with hMPV were more likely to have an underlying co‐morbidity (P= 0.11). Conclusions: Children admitted to the PICU with hMPV have a similar disease presentation and severity as children admitted with RSV, including some with extremely severe disease who require additional ventilatory or cardiovascular support. Children with hMPV are likely to be older than those with RSV, and more likely to present with pneumonia and less likely to present with bronchiolitis.     

Assessment of Real-Time 3D Visualization for Cardiothoracic Diagnostic Evaluation and Surgery Planning

Rationale and Objectives Rationale and Objectives: Three-dimensional (3D) real-time volume rendering has demonstrated improvements in clinical care for several areas of radiological imaging. We test whether advanced real-time rendering techniques combined with an effective user interface will allow radiologists and surgeons to improve their performance for cardiothoracic surgery planning and diagnostic evaluation.Material and Methods Materials and Methods: An interactive combination 3D and 2D visualization system developed at the University of North Carolina at Chapel Hill was compared against standard tiled 2D slice presentation on a viewbox. The system was evaluated for 23 complex cardiothoracic computed tomographic (CT) cases including heart–lung and lung transplantation, tumor resection, airway stent placement, repair of congenital heart defects, aortic aneurysm repair, and resection of pulmonary arteriovenous malformation. Radiologists and surgeons recorded their impressions with and without the use of the interactive visualization system.Results Results: The cardiothoracic surgeons reported positive benefits to using the 3D visualizations. The addition of the 3D visualization changed the surgical plan (65% of cases), increased the surgeons confidence (on average 40% per case), and correlated well with the anatomy found at surgery (95% of cases). The radiologists reported fewer and less major changes than the surgeons in their understanding of the case due to the 3D visualization. They found new findings or additional information about existing findings in 66% of the cases; however, they changed their radiology report in only 14% of the cases.Conclusion Conclusion: With the appropriate choice of 3D real-time volume rendering and a well-designed user interface, both surgeons and radiologists benefit from viewing an interactive 3D visualization in addition to 2D images for surgery planning and diagnostic evaluation of complex cardiothoracic cases. This study finds that 3D visualization is especially helpful to the surgeon in understanding the case, and in communicating and planning the surgery. These results suggest that including real-time 3D visualization would be of clinical benefit for complex cardiothoracic CT cases.Supported in part by NIH RO1-CA 44060, NIH PO1-CA 47982, and NIH RO1-CA 60193.