GBA mutations in Parkinson disease: earlier death but similar neuropathological features.

BACKGROUND AND PURPOSE: Mutations in the glucocerebrosidase (GBA) gene are known to be a risk factor for Parkinson's disease (PD). Data on clinicopathological correlation are limited. The purpose of this study was to determine the clinicopathological findings that might distinguish PD cases with and without mutations in the GBA gene. METHODS: Data from the Arizona Study of Aging and Neurodegenerative Disorders were used to identify autopsied PD cases that did or did not have a GBA gene mutation. Clinical and neuropathological data were compared. RESULTS: Twelve PD cases had a GBA mutation and 102 did not. The GBA mutation cases died younger (76 vs. 81 years of age) but there was no difference in disease duration or clinical examination findings. No neuropathological differences were found in total or regional semi-quantitative scores for Lewy-type synucleinopathy, senile plaques, neurofibrillary tangles, white matter rarefaction or cerebral amyloid angiopathy scores. CONCLUSIONS: In longitudinally assessed, autopsied PD cases, those with GBA mutations had a younger age at death but there was no evidence for clinical or neuropathological differences compared to cases without GBA mutations. Due to the small GBA group size, small differences cannot be excluded.

Lunar and terrestrial planet formation in the Grand Tack scenario.

We present conclusions from a large number of N-body simulations of the giant impact phase of terrestrial planet formation. We focus on new results obtained from the recently proposed Grand Tack model, which couples the gas-driven migration of giant planets to the accretion of the terrestrial planets. The giant impact phase follows the oligarchic growth phase, which builds a bi-modal mass distribution within the disc of embryos and planetesimals. By varying the ratio of the total mass in the embryo population to the total mass in the planetesimal population and the mass of the individual embryos, we explore how different disc conditions control the final planets. The total mass ratio of embryos to planetesimals controls the timing of the last giant (Moon-forming) impact and its violence. The initial embryo mass sets the size of the lunar impactor and the growth rate of Mars. After comparing our simulated outcomes with the actual orbits of the terrestrial planets (angular momentum deficit, mass concentration) and taking into account independent geochemical constraints on the mass accreted by the Earth after the Moon-forming event and on the time scale for the growth of Mars, we conclude that the protoplanetary disc at the beginning of the giant impact phase must have had most of its mass in Mars-sized embryos and only a small fraction of the total disc mass in the planetesimal population. From this, we infer that the Moon-forming event occurred between approximately 60 and approximately 130 Myr after the formation of the first solids and was caused most likely by an object with a mass similar to that of Mars.

Formation of asteroid pairs by rotational fission.

Pairs of asteroids sharing similar heliocentric orbits, but not bound together, were found recently. Backward integrations of their orbits indicated that they separated gently with low relative velocities, but did not provide additional insight into their formation mechanism. A previously hypothesized rotational fission process may explain their formation-critical predictions are that the mass ratios are less than about 0.2 and, as the mass ratio approaches this upper limit, the spin period of the larger body becomes long. Here we report photometric observations of a sample of asteroid pairs, revealing that the primaries of pairs with mass ratios much less than 0.2 rotate rapidly, near their critical fission frequency. As the mass ratio approaches 0.2, the primary period grows long. This occurs as the total energy of the system approaches zero, requiring the asteroid pair to extract an increasing fraction of energy from the primary's spin in order to escape. We do not find asteroid pairs with mass ratios larger than 0.2. Rotationally fissioned systems beyond this limit have insufficient energy to disrupt. We conclude that asteroid pairs are formed by the rotational fission of a parent asteroid into a proto-binary system, which subsequently disrupts under its own internal system dynamics soon after formation.

Spinal cord injury in Vietnamese combat.

This report deals with the experience gained by observation and treatment of 114 Vietnamese combat injuries from December 1965 to April 1969. The report covers all aspects of rehabilitation, medical, physical and socio-economic.

Role of the unquantified electroencephalography in psychiatric research.

This paper outlines potential research applications of the unquantified (paper or digital) electroencephalography (EEG) in psychiatry. Three main areas are highlighted: first, the need for thorough familiarity with the unquantified EEG is emphasized, including the ability to confidently recognize all normal and abnormal activities that could influence further analysis of the record as well as artifacts that can contaminate the tracings; second, the fact that definitive studies relating EEG abnormalities to psychiatric symptomatology and clinical response are lacking; and third, the potential for EEG to be utilized as a tool to decrease the risk of invasive research studies is discussed.

Phase III multicenter trial comparing the efficacy of 2% dodecafluoropentane emulsion (EchoGen) and sonicated 5% human albumin (Albunex) as ultrasound contrast agents in patients with suboptimal echocardiograms.

OBJECTIVES: This study was performed to compare the safety and efficacy of intravenous 2% dodecafluoropentane (DDFP) emulsion (EchoGen) with that of active control (sonicated human albumin [Albunex]) for left ventricular (LV) cavity opacification in adult patients with a suboptimal echocardiogram. BACKGROUND: The development of new fluorocarbon-based echocardiographic contrast agents such as DDFP has allowed opacification of the left ventricle after peripheral venous injection. We hypothesized that DDFP was clinically superior to the Food and Drug Administration-approved active control. METHODS: This was a Phase III, multicenter, single-blind, active controlled trial. Sequential intravenous injections of active control and DDFP were given 30 min apart to 254 patients with a suboptimal echocardiogram, defined as one in which the endocardial borders were not visible in at least two segments in either the apical two- or four-chamber views. Studies were interpreted in blinded manner by two readers and the investigators. RESULTS: Full or intermediate LV cavity opacification was more frequently observed after DDFP than after active control (78% vs. 31% for reader A; 69% vs. 34% for reader B; 83% vs. 55% for the investigators, p < 0.0001). LV cavity opacification scores were higher with DDFP (2.0 to 2.5 vs. 1.1 to 1.5, p < 0.0001). Endocardial border delineation was improved by DDFP in 88% of patients versus 45% with active control (p < 0.001). Similar improvement was seen for duration of contrast effect, salvage of suboptimal echocardiograms, diagnostic confidence and potential to affect patient management. There was no difference between agents in the number of patients with adverse events attributed to the test agent (9% for DDFP vs. 6% for active control, p = 0.92). CONCLUSIONS: This Phase III multicenter trial demonstrates that DDFP is superior to sonicated human albumin for LV cavity opacification, endocardial border definition, duration of effect, salvage of suboptimal echocardiograms, diagnostic confidence and potential to influence patient management. The two agents had similar safety profiles.

Renal carcinoid and horseshoe kidney: a frequent association of two rare entities--a case report and review of the literature.

We report the case of a primary renal carcinoid tumor associated with a horseshoe malformation in a 43-year-old man who presented with testicular pain. The tumor was centrally located and purely solid and had features ascribed to hindgut neuroendocrine neoplasia. The relative risk of developing a carcinoid tumor in a horseshoe kidney is estimated to be x82.

Priapism secondary to penile metastasis: a report of two cases and a review of the literature.

Malignancy metastasis to the penis is an uncommon clinicopathological entity. We present two cases of malignant priapism following penile metastasis, in which the diagnosis was established by core needle biopsy of the corpus cavernosum. Primary tumors were urothelial carcinoma of the urinary bladder in one case (the patient having concomitant high-grade prostatic adenocarcinoma) and prostatic adenocarcinoma in the other. The clinicopathological features of 51 previously reported cases of penile metastasis in the recent literature are reviewed.

Delirium in the elderly.

Delirium is a state of disturbed consciousness and attention and cognition or perception, which develops acutely, fluctuates during the course of the day, and is attributable to a physical disorder. This syndrome is the focus of increasing attention in light of emerging evidence of its enormous impact in human suffering as well as patient care costs. As currently conceptualized, delirium is a threshold phenomenon in which systemic and cerebral insults are cumulative and, in most cases, are multifactorial in origin. Because delirium results from an underlying medical condition, its prognosis is dependent largely on how quickly that condition is identified and appropriately treated. A basic algorithm for initial delirium management is reviewed, which includes discontinuing noncritical medications, instituting close observation, monitoring vital signs and fluid intake and output, obtaining a complete history, performing initial laboratory studies to determine the causes, implementing environmental and psychosocial interventions, and instituting pharmacologic treatment as indicated for agitation and psychosis. The pharmacologic treatment of choice is an antipsychotic of the butyrophenone class. Benzodiazepine use is reserved for the specific treatment of alcohol and sedative withdrawal, and for adjunctive use with antipsychotic agents in treatment-refractory cases. There is growing evidence that the cognitive impairment of delirium is not entirely reversible in all patients, and it may be that delirium represents a time of significant risk for progression of underlying dementia. Preventive measures discussed in the text are, therefore, of particular importance in this population.

Serial quantitative EEG among elderly subjects with delirium.

Serial quantitative electroencephalographic (QEEG) studies were performed in 33 elderly delirious, demented, and control subjects to determine which QEEG variables were associated with changes in clinical state as measured by the Folstein Mini-mental State Examination (MMSE). Conventional EEGs and brain maps were independently rated by two electroencephalographers without knowledge of clinical diagnoses. Correlational analyses were performed using these ratings, along with numerical data from QEEG. In the delirium group (n = 15), changes in scores for the relative power map and changes in relative power in the alpha band had significant associations with changes in MMSE. In the dementia group (n = 10), changes in score for absolute power maps and changes in absolute power in the delta band had significant associations with changes in MMSE. In the control group, changes in MMSE over time were negligible. These findings have potential clinical utility in diagnosing delirium, and in providing a quantitative measure of its severity, which can be used serially.

Conventional and quantitative EEG in the diagnosis of delirium among the elderly.

This study was performed to determine whether an admission quantitative EEG (QEEG) could assist in the differential diagnosis of encephalopathy among a group of elderly subjects with delirium, dementia, and delirium coexistent with dementia. Thirty four subjects from 57 to 93 years had standard 17-channel EEG and quantitative EEG studies, using a linked-ear reference. EEGs were independently rated by two electroencephalographers blind to clinical diagnosis, using conventional criteria to assess the degree of encephalopathy. Brain maps were scored by a scale developed by the authors. Numerical data examined included mean posterior dominant frequency, absolute and relative power in the delta, theta and alpha bands, and slow-wave ratios. The grouping of experimental subjects was by the discharge diagnosis, made using DSM-III-R criteria. Stepwise discriminant analysis was performed to determine which EEG and QEEG variables were best able to distinguish cases. Variables which collectively distinguished normal from encephalopathic records were Mini-Mental State Examination scores and relative power in the alpha frequency band. Variables which collectively distinguished delirium from dementia were EEG theta activity, relative power in delta, and brain map rating. The results suggest that cross-sectional QEEG study is potentially useful in the early differential diagnosis of encephalopathy, and that the variables which distinguish normal from encephalopathic patients might differ from the variables which distinguish delirium from dementia.

Torsional sensor applications in two-phase fluids.

A solid corrosion-resistant torsional waveguide of diamond cross section has been developed to sense, online and in real-time, the characteristics of the liquid in which it is submerged. The sensor can measure, among other things, the liquid content of a bubbly medium, the density of adjacent pure liquids, the equivalent density of liquid-vapor mixtures or particulate suspensions, a suspension's concentration, and the liquid level. The sensor exploits the phenomenon that the speed of propagation of a torsional stress wave in a submerged waveguide with a noncircular cross section is inversely proportional to the equivalent density of the liquid in which the waveguide is submerged. The sensor may be used to conduct measurements along distances ranging from 20 mm to 20 m and over a wide range of temperatures and pressures, e.g., from the cryogenic temperature of liquid nitrogen, -196 degrees C, up to hot pressurized water at 300 degrees C and 7 MPa. A self-calibrating three-zone sensor and associated electronics have also been developed to compensate for any sensor inaccuracies due to operation over a wide range of temperature.

Quantitative measurement of brain electrical activity in delirium.

It has long been known that the conventional electroencephalogram (EEG) is a useful tool in the evaluation of delirium. There are moderate correlations between the amount of slowing seen on EEG and the degree of confusion or level of arousal observed among delirious patients. The usefulness of the EEG for assessment and diagnosis in this area has been limited, however, by: (a) difficulties in assessing the significance of slow-wave activity, (b) problems in detecting changes in relative EEG power, and (c) the logistical problem of lengthy recording sessions with agitated patients. This article selectively reviews the development of quantitative EEG methods and presents preliminary data from an ongoing longitudinal study of the use of these methods among elderly delirious patients. There has been little work done in applying quantitative methods to the study of delirium, and no work done that has systematically compared conventional EEG analysis to quantitative analysis. Delirium shares electrophysiological characteristics with other organic mental syndromes, however, where quantitative EEG has been shown to be useful. Furthermore, analysis of digital EEG data is inherently superior to visual inspection in assessing the distribution of EEG power among different frequency bands. Previous studies, as well as data presented here, suggest that quantitative EEG is a clinically useful supplement to the conventional EEG for the assessment of elderly patients with delirium.

Acute adrenal insufficiency as a complication of urological surgery.

Acute adrenal insufficiency postoperatively is an uncommon problem and, if unrecognized, it may cause serious morbidity and can be fatal. It can occur as the result of acute bilateral adrenal hemorrhage associated with anticoagulation, inadvertent injury to or removal of a solitary adrenal gland, or postoperative stress in an individual with incipient adrenal insufficiency. Its manifestations, such as fever, tachycardia, hypotension, lethargy, abdominal pain and gastrointestinal dysfunction, mimic the other more common postoperative complications and compound the difficulty in establishing the correct diagnosis. Once the diagnosis is made the condition is readily managed successfully. We report 3 cases of acute adrenal insufficiency occurring after salvage cystectomy, ileal replacement of the ureter and retropubic prostatectomy, which illustrate the salient clinical features, problems in diagnosis and predisposing risk factors. All 3 patients survived once the diagnosis of adrenal insufficiency was made. These cases emphasize the need to be aware of the possibility of this complication to make the correct diagnosis and to institute proper treatment.

Polyhistioma: a malignant tumor of bone and extraskeletal tissues.

Polyhistioma, a neoplasm whose basic cells are small and round like those of Ewing's sarcoma, but which differentiate into various mesenchymal structures, most often bone, is described. Those cases that produce cartilage have been called mesenchymal chondrosarcoma; the others therefore are mostly urecognized. The name "polyhistioma" is suggested in the hope that with this terminology more of these tumors will be diagnosed. Polyhistiomas are not excessively rare; they affect bone and soft tissue. Half the patients with polyhistiomas died within 2 years. Treatment has resulted in survival of over 20 years. Thirty-eight of the 144 patients with polyhistioma have survived 5 years or more following first definitive treatment. Thirty-seven cases of the disease are presented.