Lev's Syndrome: A rare case of progressive cardiac conduction disorder presenting to the emergency department

Lev's Syndrome is a rare, progressive cardiac conduction defect (PCCD) due to myocardial fibrosis first described by Maurice Lev in 1964. This condition, proposed to start in the fourth decade of life, involves a sclerotic fibro-fatty degeneration of the Bundle of His and Purkinje fibers, which Lev proposed caused increasing AV delay with age. With the prevalence of electrocardiogram (ECG) use in the emergency department (ED) for cardiac- and non-cardiac complaints, dysrhythmias can be incidentally found and confuse diagnosis and disposition. We highlight the case of an 84-year-old male who presented to the ED for acute onset of diffuse facial paresthesias with elevated blood pressure at home and was found to be significantly bradycardic on initial evaluation. On serial ECGs, the conduction rhythm changed from an initial new first-degree atrioventricular (AV) block with left bundle branch block (LBBB), to a later first-degree AV block without LBBB. Cardiology was consulted. Serial ECGs demonstrated an evolving conduction block arrhythmia consistent with Lev's Syndrome. Here we describe a case of symptomatic bradycardia found to be consistent with Lev's Syndrome.     

A Murine Monoclonal Antibody with Broad Specificity for Occupationally Relevant Diisocyanates

Diisocyanates (dNCOs) used in industrial applications are well known low molecular weight allergens. Occupational exposure is associated with adverse health outcomes including allergic sensitization and occupational asthma. In this study, we report the production and initial characterization of a dNCO-hapten specific murine IgM monoclonal antibody (mAb). Female BALB/c mice were immunized intraperitoneally with 25 μg of 4,4′-methylene diphenyl diisocyanate (MDI)-keyhole limpet hemocyanin. Following six biweekly booster immunizations, splenocytes were recovered and fused to Sp2/0-Ag14 murine myeloma cell line for hybridoma production. Hybridomas were then screened in a solid-phase indirect enzyme-linked immunosorbent assay (ELISA) against 40:1 4,4′-MDI– human serum albumin (HSA). mAb reactivity to dNCO-HSA conjugates and dNCO-HSA spiked human serum were characterized using a sandwich ELISA. One hybridoma produced a multimeric IgM mAb (15D4) that reacted with 4,4′-MDI-HSA. Sandwich ELISA analysis demonstrated comparable reactivity with other occupationally relevant dNCO-HSA adducts, including 2,4-toluene diisocyanate (TDI)-HSA, 2,6-TDI-HSA, and 1,6-hexamethylene diisocyanate (HDI)-HSA, but not other electrophilic chemical HSA conjugates. The limit of quantification (LOQ) of 4,4′-MDI-HSA, 2,4-TDI-HSA, 2,6-TDI-HSA, and 1,6-HDI-HSA sandwich ELISAs were 567.2, 172.7, 184.2, and 403.5 ng/mL (8.67, 2.60, 2.77, and 6.07 pmol/mL), respectively. In contrast, experiments using dNCO-supplemented human sera showed an increase in the detectable limit of the assay. A mAb has been produced that has potential utility for detecting mixed diisocyanate exposures in occupational environments. The mAb may have additional utility in the standardization of specific IgE detection immunoassays as well as chromatographic-mass spectrometric methods to enrich dNCO adducted HSA in the plasma of occupationally exposed workers.     

Corneal collagen cross-linking: An introduction and literature review

BackgroundThis literature review analyzes the scientific evidence available regarding corneal collagen cross-linking (CXL) as a treatment option for progressive keratectasia.MethodsA literature search was performed using dates from 1990 to August 2010 regarding CXL Specific areas of focus for the literature review include safety and efficacy of the procedure as a stand-alone treatment or when used in conjunction with Intacs^® corneal implants (Addition Technology?) or photorefractive keratectomy (PRK).ResultsA total of 50 clinical trials and studies were identified, 20 of which met the inclusion criteria. Results of the included literature support the conclusion that CXL is a safe and efficacious treatment for progressive keratectasia. The results of CXL alone have shown stabilization or improvement in the maximum keratometry readings, best-corrected visual acuity, uncorrected visual acuity, and spherical and cylinder refractive measurements. CXL has been shown to enhance the effects of Intacs and has been proven successful when used in conjunction with PRK.ConclusionCXL is an effective treatment for limiting the progression of keratectasia, thus reducing the need for penetrating keratoplasty. CXL has a similar side-effect profile and similar risk level as PRK.     

Micronucleus formation in human keratinocytes is dependent on radiation quality and tissue architecture

The cytokinesis‐block micronucleus (MN) assay was used to assess the genotoxicity of low doses of different types of space radiation. Normal human primary keratinocytes and immortalized keratinocytes grown in 2D monolayers each were exposed to graded doses of 0.3 or 1.0 GeV/n silicon ions or similar energies of iron ions. The frequencies of induced MN were determined and compared to γ‐ray data. RBE_max values ranged from 1.6 to 3.9 for primary keratinocytes and from 2.4 to 6.3 for immortalized keratinocytes. At low radiation doses ≤0.4 Gy, 0.3 GeV/n iron ions were the most effective at inducing MN in normal keratinocytes. An “over‐kill effect” was observed for 0.3 GeV/n iron ions at higher doses, wherein 1.0 GeV/n iron ions were most efficient in inducing MN. In immortalized keratinocytes, 0.3 GeV/n iron ions produced MN with greater frequency than 1.0 GeV/n iron ions, except at the highest dose tested. MN formation was higher in immortalized keratinocytes than in normal keratinocytes for all doses and radiation qualities investigated. MN induction was also assessed in human keratinocytes cultured in 3D to simulate the complex architecture of human skin. RBE values for MN formation in 3D were reduced for normal keratinocytes exposed to iron ions, but were elevated for immortalized keratinocytes. Overall, MN induction was significantly lower in keratinocytes cultured in 3D than in 2D. Together, the results suggest that tissue architecture and immortalization status modulate the genotoxic response to space radiation, perhaps via alterations in DNA repair fidelity. Environ. Mol. Mutagen. 56:22–31, 2015. © 2014 Wiley Periodicals, Inc.     

Novel variants in TUBA1A cause congenital fibrosis of the extraocular muscles with or without malformations of cortical brain development

Variants in multiple tubulin genes have been implicated in neurodevelopmental disorders, including malformations of cortical development (MCD) and congenital fibrosis of the extraocular muscles (CFEOM). Distinct missense variants in the beta-tubulin encoding genes TUBB3 and TUBB2B cause MCD, CFEOM, or both, suggesting substitution-specific mechanisms. Variants in the alpha tubulin-encoding gene TUBA1A have been associated with MCD, but not with CFEOM. Using exome sequencing (ES) and genome sequencing (GS), we identified 3 unrelated probands with CFEOM who harbored novel heterozygous TUBA1A missense variants c.1216C>G, p.(His406Asp); c.467G>A, p.(Arg156His); and c.1193T>G, p.(Met398Arg). MRI revealed small oculomotor-innervated muscles and asymmetrical caudate heads and lateral ventricles with or without corpus callosal thinning. Two of the three probands had MCD. Mutated amino acid residues localize either to the longitudinal interface at which α and β tubulins heterodimerize (Met398, His406) or to the lateral interface at which tubulin protofilaments interact (Arg156), and His406 interacts with the motor domain of kinesin-1. This series of individuals supports TUBA1A variants as a cause of CFEOM and expands our knowledge of tubulinopathies.Subject terms: DNA sequencing, Neurodevelopmental disorders     

Quantitative 3-dimensional CT analyses of fractures of the middle phalanx base

BackgroundQuantitative 3-dimensional computed tomography (3DCT) analyses can provide a more detailed understanding of fracture morphology. For fracture-dislocation of the proximal interphalangeal joint, the extent of fragmentation of the volar lip of the middle phalanx—a factor that might influence treatment—is not always apparent from radiographs. We hypothesized that there is no correlation between number of fracture fragments and the percentage of articular surface area involved in intra-articular fractures of the base of the middle phalanx using quantitative 3DCT analyses.MethodsWe used 13 computed tomography scans with a slice thickness of 1.25 mm or less to create 3-dimensional models of 15 intra-articular fractures of the base of the middle phalanx in 13 patients. We resized 3-dimensional models of a non-fractured middle phalanx of the same hand to fit the fractured middle phalanx in order to approximate the size and shape of the fractured middle phalanx in its pre-injury state. We created a heatmap to demonstrate the location of the fractured articular surface.ResultsWith the number of scans available, we did not find a significant correlation between the percentage of articular surface area involved and the number of fracture fragments. The median percentage of articular surface area involved was 46 % (range, 21–90 %). The heatmap demonstrated that the radio-volar side of the articular surface seems to be more involved than the ulnar-volar side in intra-articular fractures of the base of the middle phalanx.ConclusionQuantitative 3DCT analysis of fracture fragments provides useful information that could facilitate surgery and analysis of complex fractures of the base of the middle phalanx.Level of Evidence: IV, Basic Science Study, Anatomic Study, Imaging.     

Of Ghosts, Horses, and Psychopaths

Recognition and respect for the cultures of Native Americans constitutes a basic requirement for cancer care and education approaches. This reflection shares the insights gained in fieldwork excavations in a pre-Apache archeological site on the Cibaque reservation. Despite the ghost pollution associated with contact with the dead, the Apache invited me to be a sponsor for a young girl’s coming of age ceremony. I owed this gracious invitation to the wild horses, for the Apache had observed the horses’ responses to my calls. Since horses are considered spiritually sensitive animals, their acceptance was an indicator of my resistance to ghost pollution. Therefore, I was a strong contender as a sponsor. My days among the tribe made me a better listener and observer, and thus a better physician to the cancer patients I continue to serve as a radiologist.