A Case of Vanishing Metastatic Mass: Right Atrial Mass in the Setting of Primary Epithelioid Hemangioendothelioma of the Spine.

Epithelioid hemangioendothelioma (EHE) is a rare low-grade vascular neoplasm that is characterized as intermediate between benign hemangioma and high-grade angiosarcoma affecting 1 in 1,000,000 people worldwide. It has been described throughout the body with lung, liver, skin, and bone being the most frequent sites. Primary EHE of the spine has been reported in 56 cases so far with no correlation of age and sex. Our case highlights a rare clinical presentation, etiopathogenesis, diagnosis, and treatment of EHE of the spine with metastasis to the right atrium. This is the first documented case of EHE of the spine with metastatic spread to the heart treated with bevacizumab leading to resolution of the heart metastatic mass. Further studies are warranted to develop a treatment formula for this rare tumor, to consider combination chemotherapy and new adjuvant targeted immunotherapies to prevent progression of disease.

Paraneoplastic Seronegative Pauci-Immune Glomerulonephritis Associated with Lung Adenocarcinoma Responds to Rituximab: A Case Report.

Anti-neutrophil cytoplasmic antibodies (ANCA) play an important role in the pathogenesis of pauci-immune renal vasculitis. However, in 10% of the cases, ANCA are absent. We present a case of a 64-year-old man with a chronic untreated hepatitis C virus infection and Middle Eastern thalassemia who was ANCA-negative when he was hospitalized due to acute kidney injury and accounts for an uncommon presentation of renal vasculitis. The patient had earlier reported to have undergone local lobectomy and adjuvant chemotherapy (carboplatin/pemetrexed) for lung adenocarcinoma a month prior. IL-6 has been reported to be involved in the pathophysiological cascade causing pauci-immune glomerulonephritis amongst non-small cell lung cancer patients. Previous studies with subgroup analysis have demonstrated that ANCA negativity has been associated with more chronic glomerular lesions and less crescent formation, which tends to have a critical outcome in the renal system. However, our patient underwent kidney biopsy exhibiting active crescentic glomerulonephritis, pauci-immune type with 5 cellular crescents amongst 15 glomeruli. To our knowledge, this is the third reported case of ANCA-negative vasculitis with typical presentation on biopsy in non-small cell lung cancer patients.

Probability distributions of Markovian sodium channel states during propagating axonal impulses with or without recovery supernormality.

This study addressed a macroscopic neurophysiological phenomenon - supernormality during the recovery phase of propagating axonal impulses - in explicit chemical terms. Excitation was reconstructed numerically using the kinetic scheme of multiple-state probabilistic transitions within a population of voltage-dependent sodium channels (NaCh) derived by Vandenberg and Bezanilla ("PC" scheme). Each NaCh transition was characterized as a reversible Markov process with voltage-dependent rate constants associated with each respective directional transition. While recovery reconstructed with the Hodgkin-Huxley formalism included a supernormal period, the PC scheme did not. The present analysis showed that the occurrence and degree of supernormality with the PC scheme was determined by the relative speed of the transitions within the closed loop of the kinetic scheme; supernormality was promoted by speeding these kinetics. The analysis also showed that concurrent with supernormality, the faster loop kinetics caused (1) an elevation in the C(1) --> C(2) transitions, and (2) a reduction in the I(4) --> I(5) transitions. Thus, macroscopic functionality in information processing could be expressed in terms of probabilistic interstate transitions among a population of NaCh molecules.

Rallian "equivalent" cylinders reconsidered: comparisons with literal compartments.

In Rall's "equivalent" cylinder morphological-to-electrical transformation, neuronal arborizations are reduced to single unbranched core-conductors. The conventional assumption that such an "equivalent" reconstructs the electrical properties of the fibers it represents was tested directly; electrical properties and responses of "equivalent" cylinders were compared with those of their literal branch constituents for fibers with a single symmetrical bifurcation. The numerical solution methods were validated independently by their accurate reconstruction of the responses of an analog circuit configured with compartmental architecture to solve the cable equation for passive fibers with a symmetrical bifurcation. In passive fibers, "equivalent" cylinders misestimated the spatial distribution of voltage amplitudes and steady-state input resistance, partly due to the lack of axial current bifurcation. In active fibers with a single propagating action potential, the spatial distributions of point-to-point conduction velocity values (measured in meters/second) for a literal branch point differed significantly from those of their "equivalent" cylinders. "Equivalent" cylinders also underestimated the diameter-dependent delay in propagation through the branch point and branches, due to the larger "equivalent" diameter. Corrections to the "equivalent" cylinder did not reconcile differences between "equivalent" and literal models. However, "equivalent" and literal branch fibers had the same (a) steady-state resistance "looking into" an isolated symmetrical branch point and (b) geometry-independent point-to-point propagation velocity when measured in space constants per millisecond except within +/-1 space constant from the geometrical inhomogeneity. In summary, Rall's "equivalent" cylinders did not accurately reconstruct all passive or active electrophysiological properties and responses of their literal compartments. For the modeling of individual neurons, the requirement of single-branch resolution is discussed.

Computation of high safety factor impulse propagation at axonal branch points.

The propagation of single impulses at axonal branch points and widenings was computed numerically. Previous computational studies have held that an action potential propagates across an unmyelinated axonal branch point with diameter-dependent lowered likelihood, such that increasingly complex arborizations could eliminate propagating information. This result is counter-intuitive to the principle of information divergence within neuronal circuits. The present study re-examined this result. The boundary conditions at a branch point were extracted from a physical analog circuit with actual branches. The main results were that impulse propagation was reliable past branch points and widenings, and that conduction velocity changed spatially as a function of fiber geometrical inhomogeneity.

Factors associated with unplanned hospital readmission among patients 65 years of age and older in a Medicare managed care plan.

PURPOSE: Unplanned hospital readmission within 30 days of discharge is considered a "sentinel event" for poor quality. Patients at high risk for this adverse event could be targeted for interventions designed to reduce their risk of readmission. The purpose of this study was to identify patient characteristics and risk factors at discharge associated with unplanned readmission within 30 days of hospital discharge. SUBJECTS AND METHODS: We performed a matched case-control study among patients in a Medicare managed care plan who had been admitted to an academic hospital. The cases were patients aged 65 years or older who were urgently or emergently readmitted to the hospital within 30 days of discharge. One control patient who was not readmitted within 30 days was matched to each case by principal diagnosis. The medical records of the first admission of the cases and the admission of the controls underwent review (blinded to case-control status) to determine the patient's baseline demographic characteristics, comorbid conditions, previous health care utilization, and functional status. The records were also reviewed to assess risk factors on discharge, including clinical instability, inability to ambulate and feed, mental status changes, number of discharge medications, and discharge disposition. RESULTS: Five factors were independently associated (P < 0.05) with unplanned readmission within 30 days. These included four baseline patient characteristics: age 80 years or older [odds ratio = 1.8; 95% confidence interval (CI), 1.02-3.2], previous admission within 30 days (odds ratio = 2.3; 95% CI, 1.2-4.6), five or more medical comorbidities (odds ratio = 2.6; 95% CI, 1.5-4.7), and history of depression (odds ratio = 3.2; 95% CI, 1.4-7.9); and one discharge factor: lack of documented patient or family education (odds ratio = 2.3; 95% CI, 1.2-4.5). CONCLUSIONS: If validated, these factors may identify patients at high risk of readmission. They suggest that interventions, such as improved discharge education programs, may reduce unplanned readmission.

Nifedipine gastrointestinal therapeutic system versus nifedipine coat-core: comparison of efficacy via 24-hour ambulatory blood pressure monitoring.

OBJECTIVE: To assess the comparable efficacy and adverse effect profile of two extended-release preparations of nifedipine--gastrointestinal therapeutic system (GITS) and coat-core (CC)--in patients with mild-to-moderate hypertension. DESIGN: Single institution, single-blind, prospective study. SETTING: Dwight David Eisenhower Army Medical Center, Fort Gordon, GA. PATIENTS: Ninety-one patients who were taking nifedipine GITS as a sole antihypertensive agent were randomized to receive either GITS or CC. After 3 weeks, 24-hour ambulatory blood pressure monitoring was conducted and an adverse effect questionnaire was administered. The patients were then crossed over to the other treatment arm and monitoring was repeated after 3 weeks. MEASUREMENTS: Mean blood pressure, heart rates, and the percentage of readings exceeding 140 mm Hg systolic and 90 mm Hg diastolic were compared for the 24-hour period. Additionally, mean blood pressures at 4-hour intervals after drug administration and heart rate during the first 8 hours of the dosage interval were compared. RESULTS: Ninety-one patients enrolled, 79 completed the study, and 62 patients were included in the efficacy analysis. A statistically significant difference (p = 0.020) was shown only in the last 4-hour systolic blood pressure. However, this difference was small (122 +/- 15 mm Hg with GITS vs. 126 +/- 14 mm Hg with CC). There was no difference in the percentage of readings exceeding 140 mm Hg systolic or 90 mm Hg diastolic. Neither dosage nor treatment order had an effect on the results. Adverse effects were reported with a greater frequency during CC therapy (40 with CC vs. 22 with GITS; p = 0.006), but were generally transient. Discontinuation of the drug was necessary in 3 patients during the CC cycle. CONCLUSIONS: GITS and CC demonstrated clinically equivalent antihypertensive efficacy in the study population. The CC produce may have a higher rate of adverse effects, but drug discontinuation was uncommon.

Computation of long-distance propagation of impulses elicited by Poisson-process stimulation.

1. The purpose of this work was to determine whether computed temporally coded axonal information generated by Poisson process stimulation were modified during long-distance propagation, as originally suggested by S. A. George. Propagated impulses were computed with the use of the Hodgkin-Huxley equations and cable theory to simulate excitation and current spread in 100-microns-diam unmyelinated axons, whose total length was 8.1 cm (25 lambda) or 101.4 cm (312.5 lambda). Differential equations were solved numerically, with the use of trapezoidal integration over small, constant electrotonic and temporal steps (0.125 lambda and 1.0 microsecond, respectively). 2. Using dual-pulse stimulation, we confirmed that for interstimulus intervals between 5 and 11 ms, the conduction velocity of the second of a short-interval pair of impulses was slower than that of the first impulse. Further, with sufficiently long propagation distance, the second impulse's conduction velocity increased steadily and eventually approached that of the first impulse. This effect caused a spatially varying interspike interval: as propagation proceeded, the interspike interval increased and eventually approached stabilization. 3. With Poisson stimulation, the peak amplitude of propagating action potentials varied with interspike interval durations between 5 and 11 ms. Such amplitude attenuation was caused by the incomplete relaxation of parameters n (macroscopic K-conductance activation) and h (macroscopic Na-conductance inactivation) during the interspike period. 4. The stochastic properties of the impulse train became less Poisson-like with propagation distance. In cases of propagation over 99.4 cm, the impulse trains developed marked periodicities in Interevent Interval Distribution and Expectation Density function because of the axially modulated transformation of interspike intervals. 5. Despite these changes in impulse train parameters, the arithmetic value of the mean interspike interval did not change as a function of propagation distance. This work showed that in theory, whereas the pattern of Poisson-like impulse codes was modified during long-distance propagation, their mean rate was conserved.

Poisson-process electrical stimulation: circuit and axonal responses.

This work describes a simple circuit which generated a highly Poisson-like sequence of pulses. Resistor noise was amplified in three series stages followed by rectification through a relatively large shunt resistance. This yielded a sequence of variable-amplitude transients, which were inverted, amplified with DC adjustment, and fed into a Schmitt trigger/multivibrator chip for pulse generation. The pulse generation frequency was modulated by the amplification of the rectified transients. The stochastic characteristics of the output pulse train were Poisson-like over a wide frequency range, as assessed using the intervent interval distribution and expectation density as steady-state and real-time estimators, respectively. In separate tests, the output pulse train was applied to forelimb cutaneous axons of the anesthetized cat; trains of elicited propagating action potentials were recorded extracellularly from individual G1 axons in the cuneate fasciculus. The stochastic properties of the action potential train differed from those of the stimulus, with longer deadtime, lower mean rate, and an early expectation density peak. These physiological responses to circuit output were similar to those elicited by other generators of Poisson-like stimulation.

Evidence for amino acid concentration gradients between CSF and extracellular fluid.

A small volume in the extracellular space of the medulla in the anesthetized cat was perfused with cisternal cerebrospinal fluid (CSF) using a push-pull technique. The recovered perfusate was a mixture of pushed CSF and the extracellular fluid. HPLC-EC analysis showed that the concentration of some primary amino acids in recovered perfusate often differed from their concentrations in CSF. These results suggested that amino acid gradients existed between CSF and the extracellular space.

Isolation of plasma membranes, Golgi bodies and mitochondria of Xenopus laevis morulae. Identification of plasma membrane proteins.

Homogenates of Xenopus morulae at the 16-32 cell stage were centrifuged on discontinuous sucrose gradients. Isolated fractions were identified by electron microscopy (EM) as mitochondria, a fraction enriched in Golgi vesicles, and plasma membranes. A special effort was made to prepare plasma membranes free of cytoplasmic contaminants. The resulting purified plasma membranes appeared morphologically identical to plasma membranes in situ. The external surface is covered with a fibrillar coat while vesicles are seen attached to their inner surface. O'Farell's method (1975) was used to obtain protein patterns of the various fractions on 2-dimensional gel electrophoresis. Each fraction displayed a specific pattern. By comparing the different patterns, it was possible to identify a group of proteins as belonging to the plasma membrane fractions. Labelling of cell surface with sulfo-N-hydroxysuccinimido-biotin together with differential extraction of proteins has allowed us to tentatively allocate these proteins in different structures of the plasma membrane fractions. The data presented in this paper corroborate and extend our ultrastructural studies on neogenesis of interblastomeric plasma membranes (Bieliavsky and Geuskens, 1990).

Autonomous mesoderm formation in blastocoelic roof explants from inverted Xenopus embryos.

Xenopus eggs, artificially fertilized, were prevented from undergoing equilibrium rotation by incubation in medium containing ficoll. Three orientations were selected: normal, with animal pole uppermost; inverted, with vegetal pole away from gravity; and an off-axis orientation, with embryos tilted approximately 90 degrees from the animal-vegetal axis. At blastula stage 8, cells forming the blastocoelic roof were cultured in isolation as explants. These cells are normally fated to from epidermis ventrally and neural derivatives dorsally. Unexpectedly, in the fragments originating from inverted or 90 degrees-off-axis embryos, axial structures were found: notochord, somites, neural cells, cement glands, and sometimes sensory organs. Inverted eggs could be exploited in studies of mesodermal specification.

Theoretical studies of impulse propagation in serotonergic axons.

Impulse propagation in small-diameter (1-3 microns) axons with inhomogeneous geometry was simulated. The fibres were represented by a series of 3 microns-long compartments. The cable equation was solved for each compartment by a finite-difference approximation (Cooley and Dodge 1966). First-order differential equations governing temporal changes in membrane potential or Hodgkin-Huxley (1952) conductance parameters were solved by numerical integration. It was assumed that varicosity and intervaricosity segments had the same specific cable constants and excitability properties, and differed only in length and diameter. A single long varicosity or a 'clump' of 3 microns-long varicosities changed the point-to-point (axial) conduction velocity within as well as to either side of the geometrically inhomogeneous regions. When 2 microns-diameter, 3 microns-long varicosities were distributed over the 1 micron-diameter fiber length as observed in serotonergic axons, mean axial conduction velocity was between that of uniform-diameter 1 and 2 microns fibers, and changed predictably with different cable parameters. Fibers with inexcitable varicosity membranes also supported impulse propagation. These simulations provided a general theoretical basis for the slow (less than 1 M/s) conduction velocity attributed to small-diameter unmyelinated varicose axons.

HPLC-EC determination of free primary amino acid concentrations in cat cisternal cerebrospinal fluid.

This paper describes an HPLC-EC method for measuring the concentrations of 9 free primary amino acids in cerebrospinal fluid (CSF) withdrawn from the cisterna magna of Nembutal-anesthetized adult cats. Amino acid derivatives were formed with o-phthalaldehyde and beta-mercaptoethanol; subsequently, excess thiol reagent was removed with iodoacetamide. During elution through a C18 5-micron column, the electrochemical detector's sensitivity was switched to accommodate the wide ranges of CSF amino acid concentrations. The analysis was acceptably precise and linear at and above the CSF levels and did not require CSF deproteinization. During the 23 min elution, the concentrations of 8 CSF amino acids were determined: alanine, asparagine, glutamate, glutamine, glycine, serine, taurine, and tyrosine; measurable concentrations were between 1 and 800 microM. The concentration of GABA was below its detection limit (0.5 microM). To assess the ability to detect small concentration increases which might occur due to experimental manipulations, the minimum detectable increments in CSF amino acid concentrations above endogenous levels were determined.

Amino acid content of rat cerebral astrocytes adapted to hyperosmotic medium in vitro.

Rat cerebral astrocytes from confluent primary cultures were grown for two weeks in medium made hyperosmotic with additional NaCl. At the time the cells were harvested (four weeks in culture), the medium osmolality of experimental cultures was approximately 600 mOsm. Amino acid, protein, and potassium contents and the cell volume were measured. Compared to cells maintained in control medium (approximately 300 mOsm), cells grown in hyperosmotic conditions had over two times the content of taurine and five times the content of glutamine. Alanine, aspartate, glutamate, glycine, and tyrosine contents also were elevated in these hyperosmotic-treated cells, while asparagine contents were unchanged relative to control cells. Cell volume and potassium content were decreased to approximately 50% of control levels by the hyperosmotic treatment while total protein content per cell was unchanged relative to cells from control cultures. Seven min after hyperosmotic-exposed cells were rapidly diluted into PBS with osmolality equal to about 330 mOsm, cell contents of alanine, asparagine, glutamine, glutamate, glycine, taurine, and tyrosine fell toward control levels. The data indicate that significant alterations in intracellular osmolytes occur in astrocytes adapted to hyperosmotic conditions. We suggest that a loss of intracellular potassium is at least partially compensated by accumulation of taurine, glutamine, and perhaps other amino acids acting as intracellular osmolytes.

Random-sequence stimulation of the G1 hair afferent unit.

Impulse trains were recorded from the parent axon of the cat G1 hair afferent unit. Separate random (Poisson-like) trains of mechanical stimuli were applied to two coinnervated receptive field hairs individually or concurrently. The objective was to determine whether the parent axonal impulse train elicited by dual-hair stimulation was due to a temporal combining ("mixing"; Fukami, 1980) of the impulse trains elicited in the parent axons by the same stimulation to each hair alone. Both impulse rates and patterns were assessed. During single-hair random stimulation, impulse trains differed from stimulus trains, having lower mean rates and short-interval doublets. During dual-hair random stimulation, mean impulse frequencies were on average 36% less than those predicted for mixing. There were no correlations between stimulus amplitude and departures from mixing. As a further test of the mixing hypothesis, the two single-hair-elicited impulse trains were temporally merged (i.e., superimposed to form one impulse train). Such merged impulse trains were compared with the corresponding dual-hair-elicited impulse train. Dual-hair-elicited frequencies were typically less than those of the merged trains, despite the use of an absolute-refractory-period criterion during merging. The impulse patterns elicited by dual-hair stimulation usually differed from the merged-train patterns. Temporal coupling between stimuli and impulses was either variable or absent during single-hair random stimulation; such coupling was altered during dual-hair random stimulation. In summary, this work showed that the dual-hair responses could not be predicted from the single-hair responses. Limitations of the mixing hypothesis and possible biophysical mechanisms in the axonal arborization are discussed. The results are consistent with a general hypothesis of analog processing within the arborization of the parent axon.

Presence of high molecular weight glycans on the surface of germ and embryonic cells of Xenopus laevis.

Xenopus laevis male germ cells, fertilized eggs and gastrula cells were labelled with 3H labelled sodium borohydride reduction after galactose oxidase treatment. After pronase digestion, the bulk of the label is carried by high molecular weight glycans (greater than or equal to 6,000 D). The high molecular weight of these labelled glycans and their susceptibility to degradation by endo-beta-galactosidase suggest that they may be related to the polylactosaminoglycans.

Intraoperative ultrasound in the conservative resection of testicular neoplasms.

In a series of approximately 400 patients investigated for oligospermia 4 had small testicular tumors demonstrated by high resolution real-time ultrasound. The lesions ranged in size from 3 to 6 mm., were clinically impalpable and were demonstrated on repeated sonograms. Exploration was done in all 4 patients with the aid of intraoperative high resolution ultrasound. This procedure allowed for conservative resection of the tumor with preservation of the testicle. The pathological diagnosis in all cases was benign Leydig cell tumor.

Identification of gamma-aminobutyric acid-like immunoreactive neurons in the rat cuneate nucleus.

Neurons in the cuneate nucleus of the rat were examined for gamma-aminobutyric acid-like immunoreactivity (GABA-LI) using antiserum raised against GABA-glutaraldehyde-keyhole limpet hemocyanin. GABA-LI neurons were analyzed for size, shape, and distribution and compared to Nissl-stained neurons. GABA-LI cell bodies were located at all rostral-caudal levels and were distributed randomly throughout the nucleus except at the level of the obex, where they were limited to the peripheral region of the cuneate nucleus. GABA-LI cell bodies had a significantly smaller mean cross-sectional area than the total cuneate neuronal population and comprised 21.5% of the total neuronal population as assessed with Nissl-staining. These results are consistent with the hypothesis that GABA is involved in processing somatosensory information in the rat dorsal column nuclei.