Aeroacoustic catastrophes: upstream cusp beaming in Lilley's equation.

The downstream propagation of high-frequency acoustic waves from a point source in a subsonic jet obeying Lilley's equation is well known to be organized around the so-called 'cone of silence', a fold catastrophe across which the amplitude may be modelled uniformly using Airy functions. Here we show that acoustic waves not only unexpectedly propagate upstream, but also are organized at constant distance from the point source around a cusp catastrophe with amplitude modelled locally by the Pearcey function. Furthermore, the cone of silence is revealed to be a cross-section of a swallowtail catastrophe. One consequence of these discoveries is that the peak acoustic field upstream is not only structurally stable but also at a similar level to the known downstream field. The fine structure of the upstream cusp is blurred out by distributions of symmetric acoustic sources, but peak upstream acoustic beaming persists when asymmetries are introduced, from either arrays of discrete point sources or perturbed continuum ring source distributions. These results may pose interesting questions for future novel jet-aircraft engine designs where asymmetric source distributions arise.

Resection of a catecholamine-elaborating retroperitoneal paraganglioma invading the inferior vena cava.

Paragangliomas are rare tumors originating outside of the adrenal medulla which can be associated with catecholamine secretion or mass effect, one of which typically leads to their discovery. The differences between these tumors and traditional intra-adrenal pheochromocytomas are a subject of recent investigations. Standard of care therapy is medical management and surgical resection of the tumor. When tumors are biochemically active, medical optimization of the autonomic nervous system is a critical component to a safe, definitive resection. Tumors arising in the retroperitoneum present technical challenges for the surgeon as they are often large and difficult to access, making an oncologic resection much more difficult. Lastly, these tumors are mostly benign and rarely invade adjacent structures-an operative finding not always predicted by preoperative imaging-which, if present, adds significant complexity and risk to the resection. A case illustrating these challenges in the management of a biochemically active retroperitoneal paraganglioma invading the inferior vena cava follows.

Selective vulnerability of hippocampal cornu ammonis 1 pyramidal cells to excitotoxic insult is associated with the expression of polyamine-sensitive N-methyl-D-asparate-type glutamate receptors.

Excess glutamate release and stimulation of post-synaptic glutamatergic receptors have been implicated in the pathophysiology of many neurological diseases. The hippocampus, and the pyramidal cell layer of the cornu ammonus 1 (CA1) region in particular, has been noted for its selective sensitivity to excitotoxic insults. The current studies examined the role of N-methyl-D-aspartate (NMDA) receptor subunit composition and sensitivity to stimulatory effects of the polyamine spermidine, an allosteric modulator of NMDA NR2 subunit activity, in hippocampal CA1 region sensitivity to excitotoxic insult. Organotypic hippocampal slice cultures of 8 day-old neonatal rat were obtained and maintained in vitro for 5 days. At this time, immunohistochemical analysis of mature neuron density (NeuN); microtubule associated protein-2(a,b) density (MAP-2); and NMDA receptor NR1 and NR2B subunit density in the primary cell layers of the dentate gyrus (DG), CA3, and CA1 regions, was conducted. Further, autoradiographic analysis of NMDA receptor distribution and density (i.e. [(125)I]MK-801 binding) and spermidine (100 microM)-potentiated [(125)I]MK-801 binding in the primary cell layers of these regions was examined. A final series of studies examined effects of prolonged exposure to NMDA (0.1-10 microM) on neurodegeneration in the primary cell layers of the DG, CA3, and CA1 regions, in the absence and presence of spermidine (100 microM) or ifenprodil (100 microM), an allosteric inhibitor of NR2B polypeptide subunit activity. The pyramidal cell layer of the CA1 region demonstrated significantly greater density of mature neurons, MAP-2, NR1 and NR2B subunits, and [(125)I]MK-801 binding than the CA3 region or DG. Twenty-four hour NMDA (10 microM) exposure produced marked neurodegeneration (approximately 350% of control cultures) in the CA1 pyramidal cell region that was significantly reduced by co-exposure to ifenprodil or DL-2-Amino-5-phosphonopentanoic acid (APV). The addition of spermidine significantly potentiated [(125)I]MK-801 binding and neurodegeneration induced by exposure to a non-toxic concentration of NMDA, exclusively in the CA1 region. This neurodegeneration was markedly reduced with co-exposure to ifenprodil. These data suggest that selective sensitivity of the CA1 region to excitotoxic stimuli may be attributable to the density of mature neurons expressing polyamine-sensitive NR2B polypeptide subunits.

Improved jet noise modeling using a new time-scale.

To calculate the noise emanating from a turbulent flow using an acoustic analogy knowledge concerning the unsteady characteristics of the turbulence is required. Specifically, the form of the turbulent correlation tensor together with various time and length-scales are needed. However, if a Reynolds Averaged Navier-Stores calculation is used as the starting point then one can only obtain steady characteristics of the flow and it is necessary to model the unsteady behavior in some way. While there has been considerable attention given to the correct way to model the form of the correlation tensor less attention has been given to the underlying physics that dictate the proper choice of time-scale. In this paper the authors recognize that there are several time dependent processes occurring within a turbulent flow and propose a new way of obtaining the time-scale. Isothermal single-stream flow jets with Mach numbers 0.75 and 0.90 have been chosen for the present study. The Mani-Gliebe-Balsa-Khavaran method has been used for prediction of noise at different angles, and there is good agreement between the noise predictions and observations. Furthermore, the new time-scale has an inherent frequency dependency that arises naturally from the underlying physics, thus avoiding supplementary mathematical enhancements needed in previous modeling.

Intra-cornu ammonis 1 administration of the human immunodeficiency virus-1 protein trans-activator of transcription exacerbates the ethanol withdrawal syndrome in rodents and activates N-methyl-D-aspartate glutamate receptors to produce persisting spatial learning deficits.

Human immunodeficiency virus-1 (HIV-1) infection may produce neurological deficits, such as cognitive decline, that may be worsened by concurrent ethanol (EtOH) abuse. Among the many biochemical cascades likely mediating HIV-1-associated neuronal injury is enhancement of N-methyl-d-aspartate (NMDA) receptor function and progression to excitotoxicity, an effect that may be directly or indirectly related to accumulation in brain of the HIV-1 trans-activator of transcription (Tat) factor. The present studies were designed to examine the hypothesis that binge-like EtOH pre-exposure would enhance effects of Tat on NMDA receptor function. These studies employed a modified in vivo binge EtOH exposure regimen designed to produce peak blood EtOH levels (BEL) of <200 mg/dl in adult male rats and were designed to examine effects of intra-hippocampal injection of Tat (0.5 microl/500 pM/2 min) on EtOH withdrawal-related behavior, spatial learning, and histological measures. Unilateral cannulae were implanted into the cornu ammonis 1 (CA1) pyramidal cell layer of animals prior to beginning a 4-day binge EtOH regimen. EtOH was administered via intragastric intubation ( approximately 3.0-5.0 g/kg) with dose determined by behavioral ratings of intoxication daily for 4 days (at 08:00, 16:00, and 24:00 h). EtOH withdrawal behaviors were monitored 12 h after the last administration of EtOH. Morris water maze learning was assessed during the following 4 days, at which times brains were harvested for autoradiographic measurement of NMDA receptor density and neuroinflammation. Maximal BELs of 187.69 mg/dl were observed 60 min after EtOH administration on day 2 of the regimen. In contrast, peak BELs of approximately 100 mg/dl were observed 60 min after EtOH administration on day 4 of the regimen, suggesting development of metabolic tolerance. Significant behavioral abnormalities were observed in EtOH withdrawn animals, including tremor and seizures. Intra-CA1 region injection of Tat significantly potentiated EtOH withdrawal behavioral abnormalities, an effect that was reduced by MK-801 pre-exposure. While EtOH withdrawn animals showed learning similar to control animals, EtOH withdrawn animals that received intra-CA1 Tat injection demonstrated persisting deficits in spatial learning on days 3 and 4 of training, effects that were markedly reduced by administration of the competitive NMDA receptor antagonist MK-801 30 min prior to Tat injection. No changes in [(3)H]MK-801 binding were observed. Binding density of [(3)H]PK11195, a ligand for peripheral benzodiazepine receptors expressed on activated microglia, was elevated proximal to cannula tracks in all animals, but was not altered by EtOH or Tat exposure. These findings suggest that EtOH abuse and/or dependence in HIV-positive individuals may promote HIV-1-associated cognitive deficits by altering NMDA receptor function in the absence of microglial activation or neuroinflammation.

Microtubule-associated targets in chlorpyrifos oxon hippocampal neurotoxicity.

Prolonged exposure to organophosphate (OP) pesticides may produce cognitive deficits reflective of hippocampal injury in both humans and rodents. Recent work has indicated that microtubule trafficking is also adversely affected by exposure to the OP pesticide chlorpyrifos, suggesting a novel mode of OP-induced neurotoxicity. The present studies examined effects of prolonged exposure to chlorpyrifos oxon (CPO) on acetylcholinesterase (AChE) activity, immunoreactivity (IR) of microtubule-associated proteins, neuronal injury, and tubulin polymerization using in vitro organotypic slice cultures of rat hippocampus and bovine tubulin. Cultures were exposed to CPO (0.1-10 microM) in cell culture medium for 1-7 days, a regimen producing progressive reductions in AChE activity of 15-60%. Cytotoxicity (somatic uptake of the non-vital marker propidium iodide), as well as IR of alpha-tubulin and microtubule-associated protein-2 (a/b) [MAP-2], was assessed 1, 3, and 7 days after the start of CPO exposure. As early as 24 h after the start of exposure, CPO-induced deficits in MAP-2 IR were evident and progressive in each region of slice cultures at concentrations as low as 0.1 microM. CPO exposure did not alter alpha-tubulin IR at any time point. Concentration-dependent injury in the cornu ammonis (CA)1 pyramidal cell layer and to a lesser extent, CA3 and dentate cells, was evident 3 days after the start of CPO exposure (>or=0.1 microM) and was greatest after 7 days. Tubulin polymerization assays indicated that CPO (>or=0.1 microM) markedly inhibited the polymerization of purified tubulin and MAP-rich tubulin, though effects on MAP-rich tubulin were more pronounced. These data suggest that exposure to CPO produces a progressive decrease in neuronal viability that may be associated with impaired microtubule synthesis and/or function.

Use of the platelet function analyser (PFA-100) to quantify the effect of low dose aspirin in patients with ischaemic heart disease.

Continuing aspirin up until surgery in cardiac surgical patients may increase peri-operative blood loss. It is possible that there is a subset of patients particularly sensitive to aspirin. The platelet function analyser (PFA-100) can demonstrate the antiplatelet effect of aspirin. This study was designed to assess the effect of daily 75 mg aspirin on platelet function, as measured by the PFA-100, in 92 patients with ischaemic heart disease. Patients were classified into three groups according to their PFA-100 results; aspirin hyper-responders (16%), aspirin normal responders (33%) and aspirin non-responders (51%). The PFA-100 has potential as a screening tool to identify patients who are either hyper-responsive or resistant to aspirin. Pre-operative PFA-100 screening to isolate aspirin hyper-responders could enable the vast majority of patients to continue with aspirin therapy pre-operatively, avoiding the risks of stopping treatment.

Corticosterone and dexamethasone potentiate cytotoxicity associated with oxygen-glucose deprivation in organotypic cerebellar slice cultures.

Many patients display elevated levels of serum cortisol following acute ischemic stroke. Given that glucocorticoids may potentiate some forms of insult, these studies examined the effects of corticosterone or dexamethasone exposure on cytotoxicity following oxygen-glucose deprivation in the cerebellum, a brain region susceptible to stroke. In organotypic cerebellar slice cultures prepared from neonatal rat pups, 90-min of oxygen-glucose deprivation at 15 days in vitro resulted in significant cytotoxicity at 24-, 48-, and 72-h post-oxygen-glucose deprivation, as measured by uptake of propidium iodide. Exposure of cultures following oxygen-glucose deprivation to the antioxidant trolox (500 microM), but not to the glucocorticoid receptor antagonist RU486 (10 microM), completely blocked oxygen-glucose deprivation-induced cytotoxicity. Corticosterone (1 microM) or dexamethasone (10 microM) exposure alone did not significantly increase propidium iodide uptake above levels observed in control cultures. However, corticosterone or dexamethasone exposure after oxygen-glucose deprivation potentiated oxygen-glucose deprivation-mediated propidium iodide uptake at each time point. Trolox, as well as RU486, co-exposure of cultures to corticosterone or dexamethasone after oxygen-glucose deprivation abolished all cytotoxicity. In conclusion, these data demonstrated that glucocorticoid exposure modulated oxygen-glucose deprivation-mediated propidium iodide uptake, which likely involved glucocorticoid receptor activation and pro-oxidant effects.

Thiamine deficiency in the pathogenesis of chronic ethanol-associated cerebellar damage in vitro.

Nutritional deficiencies associated with long-term ethanol consumption may cause neuronal damage in ethanol-dependent individuals. Thiamine deficiency, in particular, is thought to contribute to ethanol-associated cerebellar degeneration, although damage may occur in adequately nourished alcoholics. Thus, the present study examined the effects of thiamine depletion and ethanol exposure on cytotoxicity in rat cerebellum. Organotypic cerebellar slice cultures were treated starting at 25 days in vitro with 100 mM ethanol for 11 days or 10 days followed by a 24-h withdrawal period. This exposure paradigm has previously been shown in hippocampal slice cultures to result in spontaneous cytotoxicity upon ethanol withdrawal. Additional cerebellar cultures were exposed to the thiamine depleting agent pyrithiamine (10-500 microM) for 10 or 11 days, some in the presence of ethanol exposure or withdrawal. Other cultures were co-exposed to thiamine (1-100 microM), 500 microM pyrithiamine, and ethanol for 10 or 11 days. The results demonstrated that neither 11-day ethanol treatment nor withdrawal from 10-day exposure significantly increased cerebellar cytotoxicity, as measured by propidium iodide fluorescence. The 11-day treatment with 100 or 500 microM pyrithiamine significantly increased propidium iodide fluorescence approximately 21% above levels observed in control tissue. Cultures treated with both ethanol (11 days or 10 days plus withdrawal) and 500 microM pyrithiamine displayed a marked increase in cytotoxicity approximately 60-90% above levels observed in control cultures. Pyrithiamine and ethanol-induced cytotoxicity was prevented in cultures co-exposed to thiamine (10-100 microM) for the duration of pyrithiamine treatment. Findings from this report suggest that the cerebellum may be more sensitive to the toxic effects of thiamine deficiency, as compared with alcohol withdrawal, associated with alcohol dependence.

The prevalence of overweight adults living in a rural and remote community. The Bella Coola Valley.

OBJECTIVE: To determine the prevalence of overweight adults living in the Bella Coola Valley. DESIGN: A retrospective chart review of all people attending the Bella Coola Medical Clinic, and residing in the Bella Coola Valley. MAIN OUTCOME MEASURES: Weight (killograms) and body mass index (BMI). RESULTS: More than 92% of clinic charts had a recent measurement of weight and 65% of clinic charts had height measured; accordingly, we were able to calculate the BMI on 65% of the clinic population. Over 50% of the adults residing in the Bella Coola Valley are considered overweight (BMI > 27, the Health Canada definition) and only 25% have a BMI within an acceptable range (20.0 to 24.9). Proportionately more Aboriginal people are overweight (65%) than non-Aboriginal people (47%); men and women were similarly overweight (56% and 53%, respectively); and proportionately more people were overweight with increased age. The prevalence of being overweight in people aged 65 years and older is 66%. As weight increased so did the prevalence of diabetes mellitus, hypertension, hypercholesterolemia, diverticular disease, dyspepsia/gastroesophageal reflux disease (GERD), alcohol issues, asthma, depression, coronary artery disease, and eczematous dermatitis. There was no relationship between increasing weight and atrial fibrillation, cerebrovascular disease, inflammatory arthritis, hypothyroidism, chronic back/neck pain, peripheral vascular disease, chronic obstructive lung disease, congestive heart failure, and cancer. CONCLUSION: Living in a remote community does not protect against obesity and the complications of obesity. Obesity is present in a greater proportion of Aboriginal people. The treatment and prevention of obesity in rural populations of differing ethnicity may need to be individualized.

(-)-nicotine ameliorates corticosterone's potentiation of N-methyl-d-aspartate receptor-mediated cornu ammonis 1 toxicity.

Hypercortisolemia, long-term exposure of the brain to high concentrations of stress hormones (i.e. cortisol), may occur in patients suffering from depression, alcoholism, and other disorders. This has been suggested to produce neuropathological effects, in part, via increased function or sensitivity of N-methyl-d-aspartate (NMDA)-type glutamate receptors. Given that cigarette smoking is highly prevalent in some of these patient groups and nicotine has been shown to reduce toxic consequences of NMDA receptor function, it may be suggested that nicotine intake may attenuate the neurotoxic effects of hypercortisolemia. To investigate this possibility, organotypic hippocampal slice cultures derived from rat were pre-treated with corticosterone (0.001-1 microM) alone or in combination with selective glucocorticoid receptor antagonists for 72-h prior to a brief (1-h) NMDA exposure (5 microM). Pre-treatment with corticosterone (0.001-1 microM) alone did not cause hippocampal damage, while NMDA exposure produced significant cellular damage in the cornu ammonis (CA)1 subregion. No significant damage was observed in the dentate gyrus or CA3 regions following NMDA exposure. Pre-treatment of cultures with corticosterone (0.1-1 microM) markedly exacerbated NMDA-induced CA1 and dentate gyrus region damage. This effect in the CA1 region was prevented by co-administration of the glucocorticoid receptor antagonist RU486 (>or=1 microM), but not spironolactone (1-10 microM), a mineralocorticoid receptor antagonist. In a second series of studies, both acute and pre-exposure of cultures to (-)-nicotine (1-10 microM) significantly reduced NMDA toxicity in the CA1 region. Co-administration of cultures to (-)-nicotine (1-10 microM) with 100 nM corticosterone prevented corticosterone's exacerbation of subsequent CA1 insult. This protective effect of (-)-nicotine was not altered by co-exposure of cultures to 10 microM dihydro-beta-erythroidine but was blocked by co-exposure to 100 nM methyllycaconitine, suggesting the involvement of nicotinic acetylcholine receptors possessing the alpha7* subunit. The present studies suggest a role for hypercortisolemia in sensitizing the hippocampal NMDA receptor system to pathological activation and indicate that prolonged nicotine exposure attenuates this sensitization. Thus, it is possible that one consequence of heavy smoking in those suffering from hypercortisolemia may be a reduction of neuronal injury and sparing of cellular function.

Acute cardiac herniation after radical pleuropneumonectomy.

Acute cardiac herniation after radical pneumonectomy is extremely rare and is associated with an immediate mortality greater than 50%. We report a patient in whom cardiac herniation produced no signs or symptoms. The heart was returned to its correct position and the pericardial defect was repaired.

Traveling-wave relaxation in elongated liquid crystal cells.

We have made a theoretical study of Freedericksz relaxation in a long thin nematic liquid crystal cell subject to strong anchoring on the short ends and weak anchoring on the long sides. On removing an imposed magnetic field, three different types of relaxation behavior may be observed. Two of these are simple generalizations of one-dimensional relaxation channels, and are dominated by either the ends or the sides. The third is a traveling wave, nucleated by the strong anchoring ends of the cell but driven by the weak anchoring sides and is the result of a subtle balance between the two classical mechanisms. A phase diagram is derived, identifying the relaxation regimes as a function of the nondimensional initial field and the anchoring strength in the long cell limit. A comparison is made between numerical results and a simple one-dimensional theory derived from an asymptotic analysis. Surprisingly, the traveling wave behavior occurs for a large region of parameter space.