A right atrial mass: thrombus, tumour or other?
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Aged↗
Biomedical subjects
H Eisenberg
Publications and source records attributed to H Eisenberg.
Use of the LandmarXtrade mark Surgical Navigation System in Lateral Skull Base and Temporal Bone Surgery.
Despite the widespread availability of surgical navigation devices, their use in lateral skull base and temporal bone surgery has been limited. Problems with current systems include difficulty of use and inadequate accuracy. We present a series of cases using the LandmarXtrade mark surgical navigation system as an adjunct for lateral skull base and temporal bone procedures. This infrared emitting diodes (IRED)-driven system has a post that carries the IREDs and bypasses the need to place the patient in a Mayfield head holder. This configuration allows greater mobility of the surgical field. Registration of the patient can include a combination of fiducial and anatomic landmarks that significantly increase accuracy compared to fiducial calibration alone. We introduced the use of the lateral process of the malleus as a landmark, thereby increasing accuracy within the temporal bone to a range of 0.9 to 1.5 mm. We used the system on encephaloceles, glomus tumors, meningiomas, and schwannomas, and revision surgery for chronic otitis media. It decreased operating time, allowed more effective use of "keyhole" approaches, and increased safety. As the availability and flexibility of these systems increase, their use should become the standard of care in revision temporal bone and lateral skull base procedures.
Journal Article↗
Analytical ultracentrifugation in a Gibbsian perspective.
The analytical ultracentrifuge has come into new intensive use following complete instrumental redesign and the use of advanced computer technologies for the analysis and interpretation of experimental results. Major attention is now devoted to the evaluation of interactions between similar and dissimilar biological macromolecules in dilute and concentrated systems. Electrostatically charged biological solute systems additionally comprise low molecular weight charged and non-charged cosolvents. Solvent/cosolvent interactions, insufficiently considered in most current analytical ultracentrifugation analyses, may quantitatively affect solute/solute interactions. For comprehensive analysis the Svedberg derivation considering a buoyant molar mass (1 - rho0 partial specific volume)M2 and valid at vanishing solute concentration for strictly two component systems only, should be replaced, following classical thermodynamic analysis, by the ratio (delta rho/delta c2)(mu)/d pi/dc2 of the density increment at constant chemical potential of diffusible cosolvents, to the derivative of the osmotic pressure with solute concentration. Disregard of the solvent/cosolvent and solute/cosolvent interactions should be avoided.
Centrifugation, Density Gradient↗
Coronary artery calcium evaluation by electron beam computed tomography and its relation to new cardiovascular events.
Electron beam computed tomography is widely used to screen for coronary artery calcium (CAC). We evaluated the relation of CAC to future cardiovascular disease events in 926 asymptomatic persons (735 men and 191 women, mean age 54 years) who underwent a baseline electron beam computed tomographic scan. All subjects included in this report returned a follow-up questionnaire 2 to 4 years (mean 3.3) after scanning, inquiring about myocardial infarction, stroke, and revascularizations. Sixty percent of men and 40% of women had a positive scan at baseline. Twenty-eight cardiovascular events occurred and were confirmed by blinded medical record review. The presence of CAC (a total calcium score of >0) and increasing score quartiles were related to the occurrence of new myocardial infarction (p <0.05), revascularizations (p <0.001), and total cardiovascular events (p <0.001). Those with scores at or above the median (score of 5) had a relative risk of 4.5 (p <0.01) for new events. From Cox regression models, adjusted for age, gender, and coronary risk factors, the relative risks for those with scores of 81 to 270 and -271 (compared with 0) for cardiovascular events were 4.5 (p <0.05) and 8.8 (p <0.001), respectively. These data support previous reports showing CAC to be a modest predictor of future cardiovascular events.
Adult↗
Robotics in child neurosurgery.
We felt there was a need for a new device with "minimal invasive" tracking hardware, to be used in image-guided neurosurgery, and the system we designed to fill this need is now presented. It combines precision of movement, stability and self-positioning capabilities together with optically tracked registration and procedural control within the structure of a surgical microscope. The results are reduced setup time and minimal "distraction" from the procedure itself, factors of special relevance in child neurosurgery. The system is composed of a six-axis industrial robot suitable for use in the operating room, carrying a surgical microscope. Three progressive scan-synchronized infrared cameras mounted around the lenses of the scope are used to register the patient's position and track surgical instruments with reference to the registered space. Orientation of the microscope during surgery is obtained with a six-axis joystick used as a microscope handle. The system has been clinically used in 14 cases, and it has proven itself to be reliable, providing the expected performance advantages. The implementation of a tracked ultrasound or endoscope intraoperative imaging source is also described.
Brain Diseases↗
Probing protein-sugar interactions.
We have investigated the partial specific volumes (2) (ml/g), hydration, and cosolvent interactions of rabbit muscle aldolase by equilibrium sedimentation in the analytical ultracentrifuge and by direct density increment (partial differential/partial differentialc(2))(mu) measurements over a range of sugar concentrations and temperature. In a series of sugars increasing in size, glucose, sucrose, raffinose, and alpha-cyclodextrin, (partial differential/ partial differentialc(2))(mu) decreases linearly with the solvent density rho(0). These sugar cosolvents do not interact with the protein; however, the interaction parameter B(1) (g water/g protein) mildly increases with increasing sugar size. The experimental B(1) values are smaller than values calculated by excluded volume (rolling ball) considerations. B(1) relates to hydration in this and in other instances studied. It decreases with increasing temperature, leading to an increase in (2) due to reduced water of hydration electrostriction. The density increments (partial differential/ partial differentialc(2))(mu), however, decrease in concave up form in the case of glycerol and in concave down form for trehalose, leading to more complex behavior in the case of carbohydrates playing a biological role as osmolytes and antifreeze agents. A critical discussion, based on the thermodynamics of multicomponent solutions, is presented.
Animals↗
Gamma knife radiosurgery for the treatment of brain metastases.
One hundred and ninety-three patients with brain metastases from various primary sites received Gamma Knife radiosurgery (GKR) from July 1992 to August 1997 and were reviewed to evaluate their clinical outcome. Survival follow-up was available on 173 patients. Whole-brain radiation therapy was also administered to 148 of these patients. The median survival was 13.1 months from initial detection of brain metastases, and 7.5 months from GKR. Univariate and multivariate analyses were performed to determine prognostic factors that influenced survival following GKR. Enhanced survival is observed in patients with radiosensitive tumor types, supratentorial tumor, history of brain tumor resection, controlled primary site, and absent extracranial metastases. Local lesion control was obtained in 82% of the patients according to their last follow-up MRI scan. GKR is an effective means of treating patients with brain metastases.
Adult↗
Expression of nicotinic acetylcholine receptor subunits in the cerebral cortex in Alzheimer's disease: histotopographical correlation with amyloid plaques and hyperphosphorylated-tau protein.
Impairment of cholinergic transmission and decreased numbers of nicotinic binding sites are well-known features accompanying the cognitive dysfunction seen in Alzheimer's disease (AD). In order to elucidate the underlying cause of this cholinoceptive dysfunction, the expression of two pharmacologically different nicotinic acetylcholine receptor (nAChR) subunits (alpha4, alpha7) was studied in the cerebral cortex of Alzheimer patients as compared to controls. Patch-clamp recordings of 14 dissociated neurons of control cortices showed responses suggesting the existence of alpha4- and alpha7-containing functional nAChRs in the human cortex. In cortices of Alzheimer patients and controls, the pattern of distribution and the number of alpha4 and alpha7 mRNA-expressing neurons were similar, whereas at the protein level a decrease in the density of alpha4- and alpha7-expressing neurons of approximately 30% was observed in Alzheimer patients. The histotopographical correlation of nAChR expression with accompanying pathological changes, e.g. accumulation of hyperphosphorylated-tau (HP-tau) protein and beta-amyloid showed that neurons in the vicinity of beta-amyloid plaques bore both nAChR transcripts. Neurons heavily labelled for HP-tau, however, expressed little or no alpha4 and alpha7 mRNA. These results point to an impaired synthesis of nAChRs on the protein level as a possible cause of the cholinoceptive deficit in AD. Further investigations need to elucidate whether interactions of HP-tau with nAChR mRNA, or alterations in the quality of alpha4 and alpha7 transcripts give rise to decreased protein expression at the level of individual neurons.
Aged↗
Birth of the macromolecule.
The science of chemistry has made considerable advances over the last few hundred years in the characterization of "small" molecules which can be purified and studied by melting, distillation, crystallization and solubility in various liquids. When the study of "large" natural and biological molecules, limited in these properties, rose in significance at the turn of the century, it was first attempted to explain their properties by the concepts of colloid chemistry of aggregation and complex formation. The struggle for the acceptance of the concept of the natural or biological covalently bonded macromolecule, as recalled by Herman Mark, is one of the interesting chapters in recent science history. A specific phase in the establishment of the macromolecular concept centered around the development by The Svedberg of the analytical ultracentrifuge, a versatile tool of highly practical and profound thermodynamic significance.
Journal Article↗
Radiosurgery for cerebral arteriovenous malformations: assessment of early phase magnetic resonance imaging and significance of gadolinium-DTPA enhancement.
PURPOSE: To evaluate the initial changes within the nidus of arteriovenous malformations (AVMs) and to assess the reaction to the brain tissue surrounding AVMs after radiosurgery by serial magnetic resonance (MR) imaging. METHODS AND MATERIALS: Twenty-one patients, treated using 60Co gamma knife unit with cerebral AVMs, were retrospectively evaluated. Forty-seven follow-up MR images of the 21 patients were performed including 10 patients with two or more serial gadolinium enhanced studies (Gd-MR). Two or more sequential MR angiographies (MRA) were obtained in 13 patients. Three-dimensional (3D) time-of-flight MRA and two-dimensional (2D) phase contrast MRA were used in 13 patients for evaluating the flow changes of AVMs. The follow-up period after radiosurgery ranged from 3 to 30 months (average 10.8 months) and the interval time of MRI ranged from 34 days to 13 months (average 4.9 months). RESULTS: Reduction of nidus size was observed in 14 of 21 patients (67%) between 4 to 13 months on spin echo (SE) images. Complete obliteration was observed on SE images in 4 of these 14 patients; three were confirmed by conventional angiography. New hyperintense areas surrounding the nidus on T2s-weighted images (T2WI) developed in 9 of the 14 patients who showed nidus reduction between 5 to 17 months after radiosurgery; in three patients, size of the hyperintense area started to decrease between 6 to 7 months after its appearance. Probable radiation necrosis of pons developed in one patient 26 months after radiosurgery. The irradiated area within the AVM nidus was significantly enhanced in 8 of the 10 patients who underwent Gd-MR. The degrees of enhancement within the nidus increased with time in 7 of the 10 patients. Overall, total enhancement of irradiated areas was observed in four of the 10 patients; in three of the four, the enhancement decreased in size and degree, indicating nidus reduction. In three patients who had a partial volume irradiation within the nidus, the enhancing areas corresponded with the exact portions of irradiated volume. The nidus reduction was observed in 7 of the 13 patients on MRA during 5 to 13 months after radiosurgery. MRA was more useful compared to SE images in four of the seven patients in evaluating the size change of AVM nidus, feeding arteries, and draining veins. CONCLUSION: Magnetic resonance imaging and MRA were useful in assessing the progress of nidus reduction. T2-weighted imaging was sensitive to radiation-induced reaction in and around the AVM nidus. The enhancement within the AVM nidus on Gd-MR may represent the initial sign of nidus reduction and demonstrates the exact location of irradiation in the nidus. The changes of the enhancement pattern are presumed to represent the processes of nidus reduction and irradiated reaction within the AVM nidus.
Adolescent↗
Human microglia activate lymphoproliferative responses to recall viral antigens.
The capacity of adult human microglia to activate memory T-lymphocyte responses to recall viral antigens in autologous peripheral blood lymphocytes (PBL) was examined using measles and influenza viruses. Microglia and peripheral blood macrophages were isolated form 6 patients who underwent surgical brain biopsies. Microglial cultures readily expressed high levels of HLA class II molecules under basal culture conditions. However, compared to macrophages, microglia appeared to express much lower levels of CD45, a phenotype that has been associated with the ability of rat brain macrophage/microglia to present antigen. PBL were depleted of macrophages (D-PBL) and the efficacy of the depletion was assessed by a reduction in the T-cell response to concanavalin A. D-PBL were reconstituted with macrophages, microglia, or in some cases microglia pretreated with interferon-gamma (IFN gamma). It was observed that microglia were as efficient as macrophages in presenting viral antigens. Pretreatment of microglia with IFN gamma did not enhance further antigen presentation. Oligodendrocytes which lack constitutive or inducible HLA class II molecules failed to present viral antigens. The results have implications of the direct function of microglia as perpetuators and possibly initiators of immune responses to virus infection in the central nervous system compartment.
Adult↗
Life in unusual environments: progress in understanding the structure and function of enzymes from extreme halophilic bacteria.
Extreme halophilic archaea are saturated with salt and the intracellular electrolyte concentration exceeds that of the extracellular environment. Enzymes and other proteins from extreme halophilic archaea have been purified for many years and studied by biochemical and biophysical solution methodologies. They are active and stable at multimolar salt concentrations and denature below 2 to 3 M NaCl or KCl. Adaptation to these high concentrations of salt, genetic and evolutionary aspects, and the possibility of biotechnological applications are problems of considerable interest. Since the status of this fascinating field of research was reviewed in 1992, malate dehydrogenase from Haloarcula marismortui, now known to be a tetramer, was sequenced, its gene was cloned and expressed in active form, and its physical properties were redefined. A single mutation of Arg100 (in the enzyme active site) to Gln switched the enzyme specificity from malate to lactate dehydrogenase. Recent determination of its molecular structure by X-ray crystallography (O. Dym et al., in press) provides an exciting basis for the understanding of the structure and function of extreme halophilic enzymes. A major problem which so far has not been tackled in the study of extreme halophilic archaea is the understanding of protein nucleic acid interactions which are essential for the performance of biological function. Whereas the stability and activity of enzymes and other proteins can be modified to perform at high salt concentrations by use of currently known structural concepts, the existence of meaningful protein nucleic acid interactions in physiological concentrations of 4 to 5 M KCl constitutes an unsolved enigma worth intensive investigation.
Environment↗
Robot-assisted microscope for neurosurgery.
We describe the implementation of a robotic arm connected to a neurosurgical operative microscope. A force feedback sensor drives the motors of the arm in response to the positioning of the microscope by the surgeon. Computer graphic techniques allow tracking of the current position of the microscope within the volumetric reconstruction of the brain. The integration of the prototype into the neurosurgical operating room is currently being evaluated. Preliminary comments on this experimental phase are offered.
Angiography, Digital Subtraction↗
Detection of coronary artery calcium by ultrafast computed tomography and its relation to clinical evidence of coronary artery disease.
Ultrafast computed tomography (CT) was used to evaluate the relation of coronary artery calcium, a marker of atherosclerosis, with a reported history of coronary artery disease (CAD) in 928 men and 290 women (mean age 53 +/- 10 years; 11% with previous CAD). Total calcium score was calculated as the sum of each lesion-specific score, calculated as the product of pixel area and density > 130 Hounsfeld units. Total score was 3 to 6 times greater (p < 0.01) and the probability of coronary artery calcium 30 to 40% greater (p < 0.01) in patients with a reported history of myocardial infarction, positive angiography, bypass surgery or angioplasty. From score cutoffs ranging from 1 to 500 for defining calcium, a negative test was accurate 93 to 98% of the time in ruling out CAD, whereas specificity increased from 43 to 93%; however, sensitivity decreased from 92 to 42%. A score cutoff of 50 showed modest sensitivity (78%) and specificity (71%); however, the predictive value for CAD from a positive test remained low (< or = 40%), regardless of score cutoff. From multiple logistic regression, total score was also an independent indicator of CAD after considering any effects due to age, sex and other CAD risk factors. Further study is needed to document the long-term prognostic use of coronary calcium screening, including criteria that best project future risk of CAD.
Adult↗
Extracellular human T-cell lymphotropic virus type I Tax protein induces cytokine production in adult human microglial cells.
Tropical spastic paraparesis (HAM/TSP) is caused by human T-cell lymphotropic virus type I (HTLV-I) infection. Although the virus infects T cells in vivo and is capable of infecting microglia in vitro, the inflammatory demyelination has not been linked to virus in central nervous system tissue. Thus, indirect mechanisms (e.g., cytokines) could be involved in demyelination and inflammation. The ability of HTLV-I Tax protein to induce tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 in primary adult human microglia and peripheral blood macrophages (PBMs) was examined by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction (RT-PCR). Tax (20 ng/ml) induced TNF-alpha in microglia (from undetectable or low basal levels to 215-1,075 pg/ml, mean 576 +/- 375 pg/ml, n = 4) and in PBMs (70-1,900, mean 646 +/- 844 pg/ml, n = 4). This induction was dose dependent, Tax specific, and maximal at 8 hours after stimulation. IL-6 levels in microglia increased from a basal level of 368 +/- 194 to 664 +/- 270 pg/ml 24 hours after Tax stimulation. In contrast, IL-1 beta levels were modestly induced (< or = 26 pg/ml). An increase in mRNA levels of the three cytokines was observed by semiquantitative RT-PCR (TNF-alpha = 28-fold; IL-6 = 5.6-fold; IL-1 beta = 3.6-fold). Thus, in HAM/TSP, extracellular Tax released from infiltrating T cells could induce cytokine release by microglia and contribute to demyelination and inflammation in the absence of detectable virus.
Adult↗
Coronary calcium and atherosclerosis by ultrafast computed tomography in asymptomatic men and women: relation to age and risk factors.
We evaluated 675 men and 190 women who had no symptoms or history of clinical CHD, to determine the prevalence and risk factor correlates of CAC deposits as a marker of atherosclerosis. Measurements were taken noninvasively by ultrafast CT. The presence and extent of CAC deposits as measured by ultrafast CT was determined in all subjects, who also received personal and family medical history and risk factor questionnaire. The prevalence of CAC deposits increased significantly with age, ranging from 15% and 30% in men and women, respectively, < 40 years of age to 93% and 75% in those aged > or = 70 years. Prevalence and total score also increased by the number of risk factors present, although in those aged > 60 years a high prevalence (> 80% in men) of calcium was present regardless of the presence of risk factors. In multiple logistic regression, age, male gender, hypertension, diabetes, hypercholesterolemia, and obesity were independently associated with CAC deposits. These results suggest a high prevalence of atherosclerosis with increasing age and the presence of risk factors in men and women who have no symptoms. Studies to determine the prognostic value of CAC in individuals with no symptoms are needed to determine which populations may benefit most from CAC deposit screening.
Adult↗
Protein and nucleic acid hydration and cosolvent interactions: establishment of reliable baseline values at high cosolvent concentrations.
Hydration and cosolvent interactions of biological macromolecules can be derived, subject to excluded volume corrections, from studies of density increments at constant chemical potentials of diffusible solutes through a semipermeable membrane. In addition to precision density determinations of solutions dialyzed to equilibrium, the analytical ultracentrifuge, static and dynamic light and small angle X-ray and neutron scattering, and combined pairwise use of, for instance, ultracentrifugation and neutron scattering, considerably strengthen the experimental analysis and its interpretation. We have examined hydration of bovine serum albumin (BSA) in the native and denatured states, and binding of the denaturant guanidinium chloride (GdmCl) to the latter form; hydration of DNA and interaction with NaCl and CsCl; revised values of the halophilic malate dehydrogenase (hMDH) tetramer hydration and 'binding' of salts; probing of nucleosome core particle hydration as distinct from and additionally to the evaluation of volume exclusion (holes), by use of variously sized sugar related probes. Conclusions presented are compared to results from precision calorimetry and from X-ray crystallography structures, whenever applicable, and comparisons made with alternative interpretations and experimental approaches.
Light↗
Effect of positive supercoiling on DNA compaction by nucleosome cores.
We have used the analytical ultracentrifuge to measure the ability of histone octamers to compact DNA as a function of DNA supercoiling. Plasmid DNA (3.25 kb) was prepared at various linking numbers (delta Lk), ranging from -35 to +8. Relaxed plasmid (delta Lk = 0) was the least compact. We reconstituted a fixed number of nucleosome cores (either 11 or 13) on these DNAs. The dependence of the frictional coefficient of delta Lk showed that the reconstitute with an initial number of negative supercoils equal to the number of nucleosome cores was the least compact, as expected if each nucleosome core formed requires the constraint of one negative supercoil, resulting in relaxed linker DNA. With DNAs containing an initial number of negative supercoils unequal to the number of nucleosome cores, reconstitutes contained either negative or positive unconstrained supercoils. Reconstitutes with the same number of unconstrained supercoils, whether positive or negative, have similar frictional coefficients and are, therefore, compacted to similar degrees. We conclude that nucleosome cores compact positively and negatively supercoiled DNA equally well. Thus, nucleosome cores formed on positively supercoiled DNA with a superhelical density as high as +0.07 are not significantly unfolded.
Animals↗