Citations

ABSTRACTIntroduction: The objective of this study was to answer the typical questions from patients regarding the likely neurologic outcome and likelihood of recurrence when discussing peroneal intraneural ganglion cysts preoperatively. Methods: Retrospective analysis of all patients who underwent surgery for a peroneal intraneural ganglion cyst between January 1, 2000, and April 1, 2017, was performed. Postoperative neurologic outcomes and radiologic recurrences are reported. Results: There were 65 patients. Average clinical follow‐up was 14 months. Median dorsiflexion and eversion preoperatively were 2/5 and 4/5, respectively. Median dorsiflexion and eversion at last follow‐up postoperatively were 5/5. Radiologic recurrence occurred in 6 (9%) patients, all extraneural. Discussion: The data support excellent postoperative motor outcomes, despite frequent dense weakness of peroneal‐innervated musculature preoperatively. The surgical approach appears to eliminate risk of intraneural recurrence and minimizes risk of extraneural recurrence. Muscle Nerve 57: 989–993, 2018

The production of the oncometabolite 2-hydroxyglutarate (2-HG) has been associated with c-MYC overexpression. c-MYC also regulates glutamine metabolism and drives progression of asymptomatic precursor plasma cell (PC) malignancies to symptomatic multiple myeloma (MM). However, the presence of 2-HG and its clinical significance in PC malignancies is unknown. By performing 13 C stable isotope resolved metabolomics (SIRM) using U[ 13 C 6 ]Glucose and U[ 13 C 5 ]Glutamine in human myeloma cell lines (HMCLs), we show that 2-HG is produced in clonal PCs and is derived predominantly from glutamine anaplerosis into the TCA cycle. Furthermore, the 13 C SIRM studies in HMCLs also demonstrate that glutamine is preferentially utilized by the TCA cycle compared with glucose. Finally, measuring the levels of 2-HG in the BM supernatant and peripheral blood plasma from patients with precursor PC malignancies such as smoldering MM (SMM) demonstrates that relatively elevated levels of 2-HG are associated with higher levels of c-MYC expression in the BM clonal PCs and with a subsequent shorter time to progression (TTP) to MM. Thus, measuring 2-HG levels in BM supernatant or peripheral blood plasma of SMM patients offers potential early identification of those patients at high risk of progression to MM, who could benefit from early therapeutic intervention.

Intravenous infusion of oncolytic reovirus in patients leads to infection of brain tumors, infiltration by cytotoxic T cells, and up-regulation of PD-L1.

Abstract Bannwarth syndrome (BWS), an infrequent manifestation of neuroinvasive Lyme disease (LD) characterized by radiculopathy, neuropathy, and lymphocytic pleocytosis, is more commonly documented in Europe than North America. Here, we describe a cluster of 5 neuroinvasive LD cases with BWS in the upper Midwest United States between July and August 2017.

Expired gas concentrations were measured during a multibreath washin of He in one female and seven male subjects at rest (seated) and during cycle exercise at work rates of 70–210 W. In a computational model, the ventilation distribution was represented as a log-normal distribution with standard deviation (ςV˙); values of ςV˙ were obtained by fitting the output of the model to the data. At rest, ςV˙ was 0.89 ± 0.18; during exercise, ςV˙ was 0.60 ± 0.13, independent of the level of exercise. These values for the width of the functional ventilation distribution at the scale of the acinus are approximately two times larger than those obtained from anatomic measurements in animals at a scale of 1 cm3. The values for ςV˙, together with data from the literature on the width of the functional ventilation-perfusion distribution, show that ventilation and perfusion are highly correlated at rest, in agreement with anatomic data. The structural sources of nonuniform ventilation and perfusion and of the correlation between them are unknown.

Using the parenchymal marker technique, we measured pressure (P)-volume (P-V) curves of regions with volumes of ∼1 cm3 in the dependent caudal lobes of oleic acid-injured dog lungs, during a very slow inflation from P = 0 to P = 30 cmH2O. The regional P-V curves are strongly sigmoidal. Regional volume, as a fraction of volume at total lung capacity, remains constant at 0.4–0.5 for airway P values from 0 to ∼20 cmH2O and then increases rapidly, but continuously, to 1 at P = ∼25 cmH2O. A model of parenchymal mechanics was modified to include the effects of elevated surface tension and fluid in the alveolar spaces. P-V curves calculated from the model are similar to the measured P-V curves. At lower lung volumes, P increases rapidly with lung volume as the air-fluid interface penetrates the mouth of the alveolus. At a value of P = ∼20 cmH2O, the air-fluid interface is inside the alveolus and the lung is compliant, like an air-filled lung with constant surface tension. We conclude that the properties of the P-V curve of edematous lungs, particularly the knee in the P-V curve, are the result of the mechanics of parenchyma with constant surface tension and partially fluid-filled alveoli, not the result of abrupt opening of airways or atelectatic parenchyma.

We sought to investigate further the roles of sweating, ACh spillover, and nitric oxide (NO) in the neurally mediated cutaneous vasodilation during body heating in humans. Six subjects were heated with a water-perfused suit while cutaneous blood flow was measured with a laser-Doppler flowmeter. After a rise in core temperature (1.0 ± 0.1°C) and the establishment of cutaneous vasodilation, atropine and subsequently the NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) were given to the forearm via a brachial artery catheter. After atropine infusion, cutaneous vascular conductance (CVC) remained constant in five of six subjects, whereasl-NAME administration blunted the rise in CVC in three of six subjects. A subsequent set of studies using intradermal microdialysis probes to selectively deliver drugs into forearm skin confirmed that atropine did not affect CVC. However, perfusion ofl-NAME resulted in a significant decrease in CVC (37 ± 4%, P < 0.05). The results indicate that neither sweating nor NO release via muscarinic receptor activation is essential to sustain cutaneous dilation during heating in humans.

Sieck, Gary C., Louise E. Wilson, Bruce D. Johnson, and Wen-Zhi Zhan. Hypothyroidism alters diaphragm muscle development. J. Appl. Physiol. 81(5): 1965–1972, 1996.—The impact of hypothyroidism (Hyp) on myosin heavy chain (MHC) isoform expression, maximum specific force (Po), fatigability, and maximum unloaded shortening velocity ( Vo) was determined in the rat diaphragm muscle (Dia) at 0, 7, 14, 21, and 28 days of age. Hyp was induced by treating pregnant rats with 6- n-propyl-2-thiouracil (0.05% in drinking water) beginning at gestational day 10 and was confirmed by reduced plasma levels of 3,5,3′-triiodothyronine and thyroxine. MHC isoforms were separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels and analyzed by densitometry. Isometric Poand fatigue resistance of the Dia were measured in vitro at 26°C, and Vowas determined at 15°C with the slack test. Compared with control muscles, expression of MHC-slow was higher and expression of adult fast MHC isoforms was lower in Hyp Dia at all ages. The neonatal isoform of MHC continued to be expressed in the Hyp Dia until day 28. At each age, Poand fatigability were reduced and Vowas slower in the Hyp Dia. We conclude that Hyp-induced alterations in MHC isoform expression do not fully predict the changes in Dia contractile properties.

The parenchymal marker technique was used to measure regional tidal volumes of samples of lung parenchyma in four open-chest supine dogs. Radiopaque markers that had been implanted in the lower lobe were tracked by biplane video fluoroscopy during sinusoidal volume oscillations at tidal volumes of approximately 20% of total lung capacity and frequencies of 1-40 breaths/min before and after methacholine was administered by aerosol. The volumes of tetrahedrons with apexes at four markers were computed, and sine waves were fit to the data for volume vs. time for each tetrahedron. The ratio of mean regional volume to mean airway pressure decreased by 10-45% after exposure to methacholine. Dynamic lung elastance and resistance of the constricted lungs were larger than control, and both were frequency dependent. Regional elastance and resistance varied considerably among tetrahedrons, and these were also frequency dependent. The data were fit by a model in which tissue elastance was uniform and nearly equal to elastance in the control state, but small-airway resistance was high and variable. We conclude that the lung contracts under bronchoconstriction but that the increased dynamic elastance and resistance of the constricted lung may be primarily the result of nonuniform increased airway resistance at the level of the terminal bronchioles.

The objective of this study was to determine the relationship between developmental transitions in myosin heavy chain (MHC) composition and changes in maximum unloaded shortening velocity (Vo) and maximum specific force (Po) of the rat diaphragm muscle. The diaphragm was excised at postnatal days 0, 3, 7, 14, 21, and 28 and in adults. MHC isoform expression was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and laser densitometry. In muscle fiber bundles, Vo was determined at 15 degrees C by use of the “slack” test. Isometric Po was determined at 15 and 26 degrees C. Simple and stepwise regressions were used to evaluate the correlations between Vo, Po, and MHC phenotype transitions and the various developmental ages. The progressive increases in Vo and Po with age were found to be inversely correlated to MHC-neonatal isoform expression (r2 = -0.84 and -0.63, respectively) and positively correlated to MHC-2X (r2 = 0.78 and 0.57) and MHC-2B (r2 = 0.51 and 0.40) isoform expression (P < 0.001). Changes in MHC-neonatal isoform expression contributed to most of the developmental variance in Vo and Po, with changes in MHC-2X and MHC-2B expression also contributing significant increments to total variance. The postnatal increase in Vo most likely relates to differences in the actomyosin adenosinetriphosphatase activity between neonatal and adult fast MHC phenotypes. The increase in Po may reflect inherent differences in myofibrillar density, cross-bridge cycling kinetics, and/or the force produced per cross bridge among fibers composed of the different MHC isoforms.