Nosological considerations of the neurofibromatoses.

We are on the threshold of evaluating the NF1 and NF2 loci with respect to variant forms of the neurofibromatoses. Genetic mapping of NF1, gene cloning and characterization of its encoded product, neurofibromin, provides a framework for the evaluation of the variant forms of NF. This may also apply to NF2 variant forms in the near future. The mapping approach in evaluating variant forms of NF should begin with the rigorous clinical assessment of familial cases whereby the establishment of genetic linkage in families with overlap syndromes might determine if either NF1, NF2, or a separate locus is involved in the phenotype. Conditions mapping to the NF1 locus could then be screened for mutations in hopes of identifying the etiologies of the variant forms of NF. Mutation identification should provide a molecular-based classification scheme for the variant forms of NF, now tentatively divided into alternative and related forms. It is expected that the nosology of the neurofibromatoses will most certainly change as more is learned of the NF1 and NF2 loci.     

The relationship between smartphone use and subjective musculoskeletal symptoms and university students

[Purpose] The purpose of this study was to investigate the use of smartphones by university students in selected areas, their musculoskeletal symptoms, and the associated hazard ratio. [Subjects and Methods] This involved the completion of a self-administered questionnaire by dental hygiene students in Seoul, Gyeonggido, and Gyeongsangbukdo. The 292 completed copies of the questionnaire were then analyzed. [Results] The most painful body regions after the use of smartphones were found to be the shoulders and neck. In the musculoskeletal system, back pain was found to have a positive correlation with the size of the smartphone’s liquid crystal display (LCD) screen, and pain in legs and feet were found to have a negative correlation with the length of time that the smartphone was used. As a result, it was revealed that the use of a smartphone was correlated with musculoskeletal symptoms. [Conclusion] Therefore, in today’s environment, where the use of smartphones is on the rise, it is necessary to improve the ways that they are used and to develop a preventive program to alleviate the symptoms of musculoskeletal damage.Key words: Smartphone, Musculoskeletal symptoms, Prevent     

A cost savings approach to SPRED1 mutational analysis in individuals at risk for neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a clinically diagnosed autosomal dominant disorder requiring routine clinical management, particularly during the pediatric years. An overlapping disorder, Legius syndrome, at times is clinically indistinguishable from NF1 and results in a small percentage of individuals being mischaracterized. Distinguishing these two entities is increasingly important for prognosis, reproductive planning, and clinical management. The goal of our study was to evaluate the cost impact of genetic testing for patients with solely pigmentary findings. The costs of genetic testing in patients aged 1.5–18 years were modeled using a simulated population, assuming the clinical management approach of a single NF1 clinic. Two genetic testing algorithms (SPRED1 testing alone, and NF1 mutation analysis with reflex to SPRED1) were compared against a baseline of no genetic testing. The cost for SPRED1 mutation analysis for each individual meeting NF1 diagnostic criteria without neoplastic or boney manifestation, when compared to the no‐testing approach with routine follow‐up mutations between the ages of 10 and 14 years, was minimal (range of $4–$16). Based on the clinical practice of one NF1 clinic, we found that the cost difference to perform SPRED1 mutation analysis on individuals who meet diagnostic criteria for NF1 without neoplastic or boney manifestation were minimal. Therefore it is important that “when to test decisions” remain a physician/patient discussion, as individual benefits may be greatest at a different age than when it is most cost efficient. © 2013 Wiley Periodicals, Inc.     

The diagnostic value of fine needle aspiration in parotid lumps

Introduction

Fine needle aspiration (FNA) is a safe and quick method of diagnosing superficial lumps, which aids preoperative planning. However, FNA of the parotid gland has not gained the widespread acceptance noted in other head and neck lumps. The aim of this study was to determine the ability of FNA of the parotid gland to differentiate benign and malignant disease, and to determine the impact on surgical outcome.

Methods

A retrospective analysis of 201 consecutive parotid operations with preoperative FNA in a large district hospital in the UK was performed. The diagnostic characteristics were calculated for benign and malignant disease, and the impact on surgical procedure was determined.

Results

In identifying benign disease, FNA has a sensitivity of 85% and a specificity of 76%. In detecting malignant disease, FNA has a sensitivity and specificity of 52% and 92% respectively. A false positive on FNA was associated with a higher incidence of neck dissection.

Conclusions

FNA is a useful diagnostic test. However, owing to low sensitivity, it is necessary to interpret it in the context of all other clinical information.     

Differential mobilization of myeloma cells and normal hematopoietic stem cells in multiple myeloma after treatment with cyclophosphamide and granulocyte-macrophage colony-stimulating factor

Peripheral blood stem cells (PBSCs) mobilized with high-dose chemotherapy and hematopoietic growth factors are now widely used to support myeloablative therapy of multiple myeloma and effect complete remissions in up to 50% of patients with apparent extension of event- free and overall survival. Because tumor cells are present not only in bone marrow, but also in virtually all PBSC harvests, it is conceivable that autografted myeloma cells contribute to relapse after autotransplants. In this study, the kinetics of mobilization of normal hematopoietic stem cells were compared with those of myeloma cells present in PBSC harvests of 12 patients after high-dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor administration. CD34+ and CD34+Lin-Thy+ stem cell contents were measured by multiparameter flow cytometry, and myeloma cells were quantitated by immunostaining for the relevant Ig light chain and by a quantitative polymerase chain reaction for the myeloma-specific CDRIII sequence. Results indicated marked heterogeneity in the percentages of mobilized stem cells among different patients (0.1% to 22.2% for CD34+ cells and 0.1% to 7.5% for CD34+Lin-Thy+ cells, respectively). The highest proportions of hematopoietic progenitor cells were observed early during apheresis, with 9 of 12 patients mobilizing adequate amounts of CD34+ cells for 2 autotransplants (> 4 x 10(6)/kg) within the first 2 days, whereas peak levels (percent and absolute numbers) of myeloma cells were present on days 5 and 6 (0.5% to 22.0%). During the last days of collection, mobilized tumor cells exhibited more frequently high labeling index values (1% to 10%; median, 4.4%) and an immature phenotype (CD19+). The differential mobilization observed between normal hematopoietic stem cells and myeloma cells can be exploited to reduce tumor cell contamination in PBSC harvests.     

Adhesion of platelets to surface-bound fibrinogen under flow

After platelet activation, fibrinogen mediates platelet-platelet interactions leading to platelet aggregation. In addition, fibrinogen can also function as a cell adhesion molecule, providing a substratum for adhesion of platelets and endothelial cells. In this report, we studied the adhesion of platelets to surface-immobilized fibrinogen under flow in different shear rates. Heparinized whole blood containing mepacrine-labeled platelets was perfused for two minutes at various wall shear rates from 250 to 2,000 s-1 in a parallel plate flow chamber. The number of adherent fluorescent platelets was quantitated every 15 seconds with an epifluorescent videomicroscope and digital image processing system. When compared with platelet adhesion and aggregation seen on glass surfaces coated with type I bovine collagen, a significant increase in platelet adhesion was observed on immobilized fibrinogen up to wall shear rates of 800 s-1. The adherent platelets formed a single layer on fibrinogen-coated surfaces. Under identical conditions, no significant adhesion was observed on fibronectin- or vitronectin-coated surfaces. Although platelet adhesion to collagen was substantially inhibited by the platelet inhibitors prostaglandin E1 and theophylline, these inhibitors had no effect on platelet adhesion to fibrinogen. Platelets adhered to recombinant homodimeric wild-type (gamma 400-411) fibrinogen, but not to the recombinant homodimeric gamma' variant of fibrinogen. Platelet adhesion to recombinant fibrinogen with RGD to RGE mutations at positions alpha 95-97 and alpha 572-574 was similar to that with plasma-derived fibrinogen. These results show that platelets adhere to fibrinogen-coated surfaces under moderate wall shear rates, that the interaction is mediated by the fibrinogen 400-411 sequence at the carboxy-terminus of the gamma chain, and that the interaction is independent of platelet activation and the RGD sequences in the alpha chain.     

Down-modulation of neutrophil production by erythropoietin in human hematopoietic clones

In clonogenic assays of hematopoietic progenitors, high concentrations (4 U/mL) of erythropoietin (epo) reduced the formation of granulocyte- macrophage (GM) colonies and diminished the number of granulocytes formed per culture plate. Fetal progenitors were more sensitive to these effects of epo than were progenitors from adults, displaying these reductions at greater than or equal to 1 U epo/mL. The mechanism was investigated by growing fetal progenitors stimulated by recombinant GM-CSF, in the absence of epo, and when eight-cell clones first appeared, mapping their location, then adding epo, and assessing its effect on the subsequent differentiation of the clones. In the absence of epo, the clones developed exclusively into GM colonies. However, if developing clones were presented with epo, 85% matured into GM colonies, but 15% became multilineage or normoblast colonies. In addition, developing clones that were presented with epo produced colonies that contained fewer neutrophils. These effects of epo on neutrophil generation were observed with each of three varieties of recombinant epo, and also with purified human epo, but were not observed using epo that had been neutralized with rabbit anti-epo antiserum.