The first biallelic missense mutation in the FXN gene in a consanguineous Turkish family with Charcot-Marie-Tooth-like phenotype

neurogenetics - Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy with a prevalence of 1 in 2500 individuals worldwide. Here, we report three Turkish siblings from...     

Intratracheal administration of liposomal clodronate accelerates alveolar macrophage reconstitution following fetal liver transplantation

To facilitate study of alveolar macrophages in vivo, we developed a method to rapidly and efficiently replace resident alveolar macrophages with macrophages of a different (donor) genotype. Chimeric mice were generated by lethal irradiation followed by fetal liver transplantation (FLT) using green fluorescent protein (GFP) transgenic reporter mice as donors. Kinetics of peripheral blood monocyte (PBM) and alveolar macrophage reconstitution was determined 4 and 10 weeks post-FLT by quantifying the percentage of GFP+ cells. To enhance the recruitment of donor monocytes into the lung after FLT, mice were treated with intratracheal administration of liposomal clodronate to deplete host alveolar macrophages at 6 weeks post-FLT. PBM reconstitution occurred by 4 weeks after FLT (85.7+/-1.6% of CD11b+/Gr-1+ monocytes were GFP+), and minimal alveolar macrophage repopulation was observed (9.5% GFP+). By 10 weeks following FLT, 48% of alveolar macrophages were GFP+ by immunostaining of macrophages on lung tissue sections, and 55.1 +/- 1.6% of lung lavage macrophages were GFP+ by fluorescein-activated cell sorter analysis. Clodronate treatment resulted in a significant increase in GFP+ alveolar macrophages 10 weeks after FLT. By immunostaining, 90% of macrophages were GFP+ on lung tissue sections and 87.5 +/- 1.1% GFP+ in lung lavage (compared with GFP-transgenic controls). The ability of newly recruited alveolar macrophages to clear Pseudomonas aeruginosa and activate nuclear factor-kappaB in response to Eschericia coli lipopolysaccharide demonstrated normal macrophage function. Optimizing this methodology provides an important tool for the study of specific genes and their contribution to alveolar macrophage function in vivo.     

Cognition of the mothers of patients with Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) has been found to be associated with cognitive impairment. However, few studies have addressed cognitive impairment among mothers of children with DMD. In the present study, the neuropsychological profiles of both carrier mothers (C-Ms) and noncarrier mothers (NC-Ms) were examined, and the findings were compared with healthy control mothers (HC-Ms). There were 90 participants, consisting of 31 C-Ms, 24 NC-Ms, and 35 HC-Ms, each of whom completed a neuropsychological test battery. C-Ms had poorer cognition performance in attention, working memory, immediate verbal memory, visuospatial skills, and executive functions than NC-Ms, and HC-Ms. This study provides evidence that there may be cognitive impairment in mothers of patients with DMD. The cognitive impairment of C-Ms has similarities to that seen in children with DMD.     

Hereditary neuropathies

PURPOSE OF REVIEW: The purpose of this review is to help neurologists understand new concepts in hereditary neuropathies, from the clinician's point of view, in the molecular era after the burst of information regarding peripheral nerve biology. RECENT FINDINGS: Recent studies have focused on understanding the pathomechanisms involved in hereditary neuropathies. In the past year identification of new genes has slowed down since scientists have concentrated more on the function of genes causing Charcot-Marie-Tooth disease and Schwann cell-axon interactions to reveal the molecular cell biology of the disease. Animal models for the most common subtypes of human Charcot-Marie-Tooth disease are now available. SUMMARY: Rapid advances in the molecular genetics and cell biology of hereditary neuropathies have highlighted the great genetic complexity of Charcot-Marie-Tooth disease. The evolution from a simple clinical classification to a complex molecular one has not facilitated our understanding of the disease. Moreover, the new molecular classification is not simple to use as different mutations of the same gene produce a range of phenotypes. The clinicians have to look for specific clinical and electrophysiological clues to direct the patient to appropriate genetic testing.     

Aerial adulticiding for the suppression of Culex tarsalis in Kern County, California, using low-volume propoxur: 1. Selection and evaluation of the application system

Propoxur applied aerially at 4.7 liters/ha was an effective adulticide against organophosphate resistant Culex tarsalis. Applications by fixed-wing and helicopter underslung spray systems equipped with hydraulic nozzles provided good coverage of test areas as indicated by the mortality patterns of sentinel mosquitoes. However, the propoxur wettable powder in larvicide oil formulation was dispersed in a very broad particle range. The fixed-wing (Ayres Thrush) aircraft treated 260 ha (640 acres) in 45 min and could carry a full load of 1500 liters (400 gal) at temperatures in excess of 38 degrees C. In contrast, the helicopter (Bell UH-1) with an underslung spray system (Simplex Model 6800) required over 2 hrs to treat the same area at lower temperatures and could not carry a full load of 570 liters (150 gal) at temperatures greater than 38 degrees C.     

Assessment of patients with hereditary transthyretin amyloidosis – understanding the impact of management and disease progression

Timely diagnosis of hereditary variant transthyretin (ATTRv) amyloidosis is critical for appropriate treatment and optimal outcomes. Significant differences are seen between patients receiving treatment and those who are not, though disease progression may continue despite treatment in some patients. Healthcare professionals caring for patients with ATTRv amyloidosis therefore need reliable ongoing assessments to understand the continuing course of disease and make appropriate treatment choices on an individual basis. Various signs and symptoms experienced by patients may be evaluated as indicators of disease progression, though there is currently no validated score that can be used for such ongoing assessment. Recognizing this situation, a group of clinicians highly experienced in ATTR amyloidosis developed an approach to understand and define disease progression in diagnosed and treated patients with ATTRv amyloidosis. The suggested approach is based on the recognition of distinct phenotypes which may usefully inform the particular tools, tests and investigations that are most likely to be appropriate for individual patients. It is aimed at implementing appropriate and ongoing assessment of patients being treated for ATTRv amyloidosis, such that the effectiveness of management can be usefully assessed throughout the course of disease and management can be tailored according to the patient's requirements.     

Cardiac telemetry coding.

In summary, documentation of the procedure performed and individual insurance payor guidelines will determine the procedure code billed for telemetry services. Because codes accepted for these services and reimbursement guidelines may vary, it may be necessary to obtain specific guidance before claim submission.