Quantification of perfusion fMRI using a numerical model of arterial spin labeling that accounts for dynamic transit time effects.

A new approach to modeling the signal observed in arterial spin labeling (ASL) experiments during changing perfusion conditions is presented in this article. The new model uses numerical methods to extend first-order kinetic principles to include the changes in arrival time of the arterial tag that occur during neuronal activation. Estimation of the perfusion function from the ASL signal using this model is also demonstrated. The estimation algorithm uses a roughness penalty as well as prior information. The approach is demonstrated in numerical simulations and human experiments. The approach presented here is particularly suitable for fast ASL acquisition schemes, such as turbo continuous ASL (Turbo-CASL), which allows subtraction pairs to be acquired in less than 3 s but is sensitive to arrival time changes. This modeling approach can also be extended to other acquisition schemes.     

Rapid,simple identification of individual osteoblastic cells and their specific products by cell blotting assay

Biochemical and molecular biological studies of osteoblastic cell function and hormonal regulation are frequently confounded by the inherent cellular heterogeneity and phenotypic instability of existing in vitro and in vivo model systems. A new technique (derived from Western blotting or antibody-based detection of protein molecules bound to nitrocellulose paper) is described for identification of individual cells which synthesize osteoblast-specific gene products (bone Gla-protein, type I collagen, and alkaline phosphatase) or produce cAMP in response to parathyroid hormone (PTH) or isoproterenol. Dispersed primary neonatal rat calvariae or osteogenic sarcoma cells were “plated” on Immobilon-P (a hydrophobic transfer membrane with very high protein-binding capacity) for 30 minutes to several hours, followed by agonist treatment, formalin fixation, hematoxylin staining, and immunostaining with a battery of antibodies specific for osteoblastic products. Individual cells and their secretory zones were visualized by light microscopy and counted. Treatment with PTH with or without isoproterenol resulted in increases in the percentages of osteoblastic cells elaborating cAMP, as well as the intensity of immunostaining, but had no effects on MCF-7 cells, a nonosteoblastic breast carcinoma control line. The percentage of cells within each primary osteoblastic cell population isolated or rat osteogenic sarcoma cell clone (G2 or C12) that elaborated bone-specific proteins or that generated cAMP in response to PTH varied with time and the individual cellular preparation, reconfirming the cellular heterogeneity of these systems. This method, in conjunction with techniques such as in vitro hybridization, should prove useful in characterizing discrete osteoblastic bone cell subpopulations and in clarifying mechanisms of hormonal regulation by local and systemic agents.     

Surgical treatment of substernal thyroid disease

The thyroid surgeon must have a full understanding of the anatomy and surgical approaches to the mediastinum. Although most benign substernal goiters may be removed by a transcervical approach, the surgeon needs to know indications for transclavicular and median sternotomy approaches. When there is direct evidence of extension of thyroid cancer into the mediastinum, the possibility of median sternotomy should be considered. This is certainly mandated when disease extends to the inferior mediastinum. Superior mediastinal node dissection is usually easy to approach transcervically. Unilateral extension of the disease may be accessed readily with a transclavicular approach for most cases. Careful dissection of the recurrent laryngeal nerve as well as parathyroids is essential to diminish postoperative morbidity. The morbidity is a reflection of the experience and technical skills of the surgeon as well as the extent of the disease. The best results for resection of substernal thyroid disease are obtained by the experienced thyroid surgeon, not the occasional operator.     

A novel mutation in the last exon of ATRX in a patient with α-thalassemia myelodysplastic syndrome

Abstract:  We describe a patient with acquired alpha-thalassemia myelodysplastic syndrome (ATMDS). A previously healthy 66-year-old man presented with hemoglobin of 9.3 g/dL, mean corpuscular volume 59 fL, and a bone marrow aspirate with increased erythroid precursors and hypolobulated megakaryocytes. Hemoglobin H inclusions were seen in most red cells after 1% brilliant cresyl blue supravital stain of the peripheral blood. At the molecular level, we identified of a novel mutation in the most 3' exon of the ATRX gene ( C GA→ T GA substitution in codon 2407) resulting in a premature termination codon (p.R2407X). This case provides further evidence for a link between ATRX mutations and ATMDS, and suggests a possible role for the conserved Q-box element in ATRX function.     

A prototype retractor system designed to minimize ischemic brain retractor injury: initial observations

The authors have developed and patented a neurosurgical retractor system incorporating an infrared emitter and detector that allows detection of cerebral pulsations. Gentle contact with the surface of cat brains shows cerebral pulsations that correlate with arterial pulse as well as mechanical ventilation. The amplitude of cerebral pulsations decreases with higher retraction pressure and disappears at approximately 20 mmHg. The pressure on the surface of the brain decreased 50% in 5 minutes even though the position of the retractor was maintained constant. The authors postulate that monitoring cerebral pulsation may prove useful in clinical neurosurgery with respect to avoiding excessive retraction, which causes brain damage.