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Biomedical subjects

D W Roberts

Publications and source records attributed to D W Roberts.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of UVB irradiance on conidia and germinants of the entomopathogenic Hyphomycete Metarhizium anisopliae: a study of reciprocity and recovery.

We tested the effects of irradiances of 920 and 1200 mW m-2 (weighted irradiance) on the conidia and germinants of the entomopathogenic Hyphomycete Metarhizium anisopliae. The conidia were exposed to the two irradiances for 1, 2, 4, 6, 7 or 8 h. Increased exposure decreased relative percent culturability. The inactivation provoked by the irradiance of 1200 mW m-2 was higher than for the 920 mW m-2, with a reduction in the 50% lethal time (LT50) from 6 h 40 min to 4 h 26 min. Reciprocity was not observed when conidia in water suspension and germinants in different stages of the germinative process were exposed to a 17.3 kJ m-2 total dose at both irradiance levels. Although nonreciprocity was observed in all situations, its magnitude varied as a function of metabolic state and/or cell-cycle phase in which the conidia were at the exposure time. The least difference between the effects of the two irradiance levels was observed when nongerminating conidia in suspension were exposed, and the greatest was observed when conidia were exposed during an advanced germination phase. Doses of 6.6 and 17.3 kJ m-2 supplied through the two irradiance levels delayed the germination of the surviving conidia. At both doses, delay was greater during exposure to the higher irradiance. Nonreciprocity was higher for the 17.3 kJ m-2 dose. Nonreciprocity magnitude, in addition to depending on the conidial physiological state, also depended on dose. The results demonstrate the importance of evaluating the impact of the increase in irradiance during the different stages of the fungal life cycle, especially during the stages which are more sensitive to UV, and not simply in dormant conidia.

Animals↗
PubMed2001

Both solar UVA and UVB radiation impair conidial culturability and delay germination in the entomopathogenic fungus Metarhizium anisopliae.

The entomopathogenic hyphomycete Metarhizium anisopliae has been used in programs of agricultural pest and disease vector control in several countries. Exposure to simulated solar radiation for a few hours can completely inactivate the conidia of the fungus. In the present study we determined the effect of exposures to full-spectrum sunlight and to solar ultraviolet A radiation at 320-400 nm (UVA) on the conidial culturability and germination of three M. anisopliae strains. The exposures were performed in July and August 2000 in Logan, UT. The strains showed wide variation in tolerance when exposed to full-spectrum sunlight as well as to UVA sunlight. Four-hour exposures to full-spectrum sunlight reduced the relative culturability by approximately 30% for strain ARSEF 324 and by 100% for strains ARSEF 23 and 2575. The relative UV sensitivity of the two more sensitive strains was different under solar UV from that under ultraviolet B radiation at 280-320 nm (UVB) in the laboratory. Four-hour exposures to solar UVA reduced the relative culturability by 10% for strain ARSEF 324, 40% for strain ARSEF 23 and 60% for strain ARSEF 2575. Exposures to both full-spectrum sunlight and UVA sunlight delayed the germination of the surviving conidia of all three strains. These results, in addition to confirming the deleterious effects of UVB, clearly demonstrate the negative effects of UVA sunlight on the survival and germination of M. anisopliae conidia under natural conditions. The negative effects of UVA in sunlight also emphasize that the biological spectral weighting functions for this fungus must not neglect the UVA wavelengths.

Dose-Response Relationship, Radiation↗
PubMed2000

Identification of fumonisin B1 as an inhibitor of argininosuccinate synthetase using fumonisin affinity chromatography and in vitro kinetic studies.

Fumonisin B1, a fungal mycotoxin that grows on corn and other agricultural products, alters sphingolipid metabolism by inhibiting ceramide synthase. The precise mechanism of fumonisin B1 toxicity has not been completely elucidated; however, a central feature in the cytotoxicity is alteration of sphingolipid metabolism through interruption of de novo ceramide synthesis. An affinity column consisting of fumonisin B1 covalently bound to an HPLC column matrix was used to isolate a rat liver protein that consistently bound to the column. The protein was identified as argininosuccinate synthetase by protein sequencing. The enzyme-catalyzed formation of argininosuccinic acid from citrulline and aspartate by recombinant human and rat liver argininosuccinate synthetase was inhibited by fumonisin B1. Fumonisin B1 showed mixed inhibition against citrulline, aspartate, and ATP to the enzyme. Fumonisin B1 had a Ki' of approximately 6 mM with the recombinant human argininosuccinate synthase and a Ki' of 35 mM with a crude preparation of enzyme prepared from rat liver. Neither tricarballylic acid nor hydrolyzed fumonisin B1 inhibited recombinant human argininosuccinate synthetase. This is the first demonstration of fumonisin B1 inhibition of argininosuccinate synthethase, a urea cycle enzyme, which adds to the list of enzymes that are inhibited in vitro by fumonisin B1 (ceramide synthase, protein serine/threonine phosphatase). The extent of the inhibition of argininosuccinate synthetase in cells, and the possible role of this enzyme inhibition in the cellular toxicity of FB1, remains to be established.

Animals↗
PubMed2000

Pure lesionectomy versus tailored epilepsy surgery in treatment of cavernous malformations presenting with epilepsy.

Cerebral cavernous malformations (CM) are well-circumscribed vascular malformations that often present with epileptic seizures. Although patients may initially benefit from antiepileptic drugs, surgical treatment may become necessary due to medically intractable seizures. However, it is unclear whether lesionectomy alone or tailored epilepsy surgery with previous invasive monitoring is the optimal strategy in such cases. We report two patients with epileptic seizures due to CM. One patient with few seizures prior to surgery became seizure-free following resection of the CM and the surrounding tissue. In the second patient with long-lasting epilepsy, lesionectomy was performed because of the proximity to a functioning left hippocampus. This limited resection failed and the patient still had seizures. Subsequently, invasive monitoring with intracranial depth and strip electrodes was performed in order to localize the epileptogenic area and determine whether the left hippocampus could be spared. The invasive study showed the seizure origin in the tissue around the former CM but no epileptic discharges in the hippocampus. In a second operation, an anterior temporal resection was performed with removal of the epileptogenic surrounding tissue and the patient became seizure-free without cognitive deficits. The optimal surgical strategy for CM presenting with epileptic seizures must take into account various factors such as underlying mechanisms and duration of epilepsy, and location of the lesion.

Adult↗
PubMed2000

Quantitative structure-activity relationships: sulfonate esters in the local lymph node assay.

The biological activity of skin-sensitizing chemicals is related to their ability to react, either directly or after metabolic activation, with appropriate skin proteins. For direct acting electrophilic compounds, this ability can be modelled, using the RAI (relative alkylation index) approach, by a combination of electrophilicity and hydrophobicity parameters. The development of predictive quantitative structure-activity relationships (QSAR) models of skin sensitization, using mechanism-based physicochemical parameters, has been greatly facilitated by the introduction of the murine local lymph node assay (LLNA), which is able to describe the extent of the biological response in objective and quantitative terms. In the present work, sensitization response data in the LLNA is generated for a series of 6 sulfonate esters. An RAI-based hybrid QSAR/dose-response relationship is derived using a negative hydrophobicity coefficient in the RAI expression, to model the effect of retention of the hydrophobic test chemicals in the stratum corneum. Dose-response analyses are used to estimate EC3 and EC20 values as quantitative indices of skin sensitization potential for each compound, and regression analysis is applied to develop QSARs correlating these EC3 and EC20 values with an RAI-based parameter. The high statistical quality of these QSARs demonstrates both the consistency of the LLNA method for generating high quality skin sensitization data, and the value of the RAI approach in development of mathematical models for skin sensitization.

Alkylation↗
PubMed2000

In vivo quantification of a homogeneous brain deformation model for updating preoperative images during surgery.

Clinicians using image-guidance for neurosurgical procedures have recently recognized that intraoperative deformation from surgical loading can compromise the accuracy of patient registration in the operating room. While whole brain intraoperative imaging is conceptually appealing it presents significant practical limitations. Alternatively, a promising approach may be to combine incomplete intraoperatively acquired data with a computational model of brain deformation to update high resolution preoperative images during surgery. The success of such an approach is critically dependent on identifying a valid model of brain deformation physics. Towards this end, we evaluate a three-dimensional finite element consolidation theory model for predicting brain deformation in vivo through a series of controlled repeat-experiments. This database is used to construct an interstitial pressure boundary condition calibration curve which is prospectively tested in a fourth validation experiment. The computational model is found to recover 75%-85% of brain motion occurring under loads comparable to clinical conditions. Additionally, the updating of preoperative images using the model calculations is presented and demonstrates that model-updated image-guided neurosurgery may be a viable option for addressing registration errors related to intraoperative tissue motion.

Animals↗
PubMed2000

The role of intracranial electrode reevaluation in epilepsy patients after failed initial invasive monitoring.

PURPOSE: Intracranial electrode recording often provides localization of the site of seizure onset to allow epilepsy surgery. In patients whose invasive evaluation fails to localize seizure origin, the utility of further invasive monitoring is unknown. This study was undertaken to explore the hypothesis that a second intracranial investigation is selected patients warrants consideration and can lead to successful epilepsy surgery. METHODS: A series of 110 consecutive patients with partial epilepsy who had undergone intracranial electrode evaluation (by subdural strip, subdural grid, and/or depth electrodes) between February 1992 and October 1998 was retrospectively analyzed. Of these, failed localization of seizure origin was thought to be due to sampling error in 13 patients. Nine of these 13 patients underwent a second intracranial investigation. RESULTS: Reevaluation with intracranial electrodes resulted in satisfactory seizure-onset localization in seven of nine patients, and these seven had epilepsy surgery. Three frontal, two temporal, and one occipital resection as well as one multiple subpial transection were performed. Six patients have become seizure free, and one was not significantly improved. The mean follow-up is 2.8 years. There was no permanent morbidity. CONCLUSIONS: In selected patients in whom invasive monitoring fails to identify the site of seizure origin, reinvestigation with intracranial electrodes can achieve localization of the region of seizure onset and allow successful surgical treatment.

Adolescent↗
PubMed2000

An unusual complication of intracranial electrodes.

This report describes two patients who developed persistent neurologic deficits during intracranial EEG recording without clear evidence of intracranial edema or infarction. Both patients had previously received high-dose brain radiation therapy and chemotherapy. Because of this experience, we strongly caution the use of intracranial electrodes in patients with similar profiles.

Adult↗
PubMed2000

Intractable seizures of frontal lobe origin: clinical characteristics, localizing signs, and results of surgery.

PURPOSE: We analyzed the clinical characteristics of seizures of frontal lobe (FL) origin with particular emphasis on establishing different categories and determining if these categories had any localizing or lateralizing value. In addition, results of surgery are reported. METHODS: Seizure characteristics were established by historical review and electroencephalographic/videotape analysis of 449 seizures in 26 adult patients with refractory seizures of FL origin. RESULTS: No outstanding risk factor was identified for seizures of FL origin. Seizures were frequent (7.1 per week), brief (mean duration, 48.3 seconds), and had a nocturnal preponderance in 58% of the patients. Status epilepticus was reported in 54%, and generalized convulsions as a prominent seizure type were reported in 26% of patients. The most common reported aura was a nonspecific sensation, often localized to the head (35%). Early forced head and eye deviation was not a consistent lateralizing sign, whereas late head and eye deviation always occurred contralateral to the site of seizure origin. Early asymmetric tonic posturing occurred consistently contralateral to the side of seizure origin. Clinical seizure patterns did not consistently localize to specific regions of the frontal lobe, although there were some noticeable trends: focal clonic seizures were associated with seizure origin in the frontal convexity; tonic seizures were most often associated with origin in the supplementary motor area but also occurred with origin in other parts of the frontal lobe; seizures resembling typical temporal lobe seizures with oroalimentary automatisms were observed with seizure origin in the orbitofrontal region; and seizures with hyperactive, frenetic automatisms were not associated with any specific region within the frontal lobes. Eighty percent of patients had favorable seizure outcome after surgery (class I/II). CONCLUSION: Although certain clinical features are characteristic for seizures of frontal lobe origin and some have lateralizing value, they do not localize to specific areas within the FL. After careful presurgical evaluation, both lesional and nonlesional patients benefit from epilepsy surgery.

Age of Onset↗
PubMed2000

In vivo modeling of interstitial pressure in the brain under surgical load using finite elements.

Current brain deformation models have predominantly reflected solid constitutive relationships generated from empirical ex vivo data and have largely overlooked interstitial hydrodynamic effects. In the context of a technique to update images intraoperatively for image-guided neuronavigation, we have developed and quantified the deformation characteristics of a three-dimensional porous media finite element model of brain deformation in vivo. Results have demonstrated at least 75-85 percent predictive capability, but have also indicated that interstitial hydrodynamics are important. In this paper we investigate interstitial pressure transient behavior in brain tissue when subjected to an acute surgical load consistent with neurosurgical events. Data are presented from three in vivo porcine experiments where subsurface tissue deformation and interhemispheric pressure gradients were measured under conditions of an applied mechanical deformation and then compared to calculations with our three-dimensional brain model. Results demonstrate that porous-media consolidation captures the hydraulic behavior of brain tissue subjected to comparable surgical loads and that the experimental protocol causes minimal trauma to porcine brain tissue. Working values for hydraulic conductivity of white and gray matter are also reported and an assessment of transient pressure gradient effects with respect to deformation is provided.

Animals↗
PubMed2000

Frameless stereotaxy of the brain.

Today's neurosurgical journals are replete with advertisements for systems designed to provide image guidance during surgery. These so-called "frameless" stereotactic systems provide the surgeon with navigational information, relating the location of instruments in the operative field to preoperative imaging data. Such information minimizes invasiveness by more accurately selecting the best trajectory to the lesion, ensures more precise identification of normal structures, and guides complete removal of a lesion. To achieve these goals, all of these systems utilize the stereotactic principle of co-registration of the patient with an imaging study. This review will trace the development of image-guided surgery from its origins in frame-based stereotaxy to its current use as a surgical navigation methodology. A review of the more prevalent techniques and available systems will be presented, along with examples of specific applications of surgical navigation. Finally, some of the future directions of frameless stereotaxy will be discussed.

Brain↗
PubMed2000

Does performing image registration and subtraction in ictal brain SPECT help localize neocortical seizures?

UNLABELLED: Ictal brain SPECT (IS) findings in neocortical epilepsy (patients without mesiotemporal sclerosis) can be subtle. This study is aimed at assessing how the seizure focus identification was improved by the inclusion of individual IS and interictal brain SPECT (ITS)-MRI image registration as well as performing IS - ITS image subtraction. METHODS: The study involved the posthoc analysis of 64 IS scans using 99mTc-ethyl cysteinate dimer that were obtained in 38 patients without mesiotemporal sclerosis but with or without other abnormalities on MRI. Radiotracer injection occurred during video-electroencephalographic (EEG) monitoring. Patients were injected 2-80 s (median time, 13 s) after clinical or EEG seizure onset. All patients had sufficient follow-up to correlate findings with the SPECT results. All patients had ITS and MRI, including a coronal volume sequence used for registration. Image registration (IS and ITS to MRI) was performed using automated software. After normalization, IS - ITS subtraction was performed. The IS, ITS, and subtraction studies were read by 2 experienced observers who were unaware of the clinical data and who assessed the presence and localization of an identifiable seizure focus before and after image registration and subtraction. Correlation was made with video-EEG (surface and invasive) and clinical and surgical follow-up. RESULTS: Probable or definite foci were identified in 38 (59%) studies in 33 (87%) patients. In 52% of the studies, the image registration aided localization, and in 58% the subtraction images contributed additional information. In 9%, the subtraction images confused the interpretation. In follow-up after surgery, intracranial EEG or video-EEG monitoring (or both) has confirmed close or reasonable localization in 28 (74%) patients. In 6 (16%) patients, SPECT indicated false seizure localization. CONCLUSION: Image registration and image subtraction improve the localization of neocortical seizure foci using IS, but close correlation with the original images is required. False localizations occur in a minority of patients.

Adult↗
PubMed1999

Physiological consequences of ectopic agouti gene expression: the yellow obese mouse syndrome.

This review summarizes primary and downstream phenotypic manifestations, with emphasis on altered responsiveness to environmental stimuli, of dominant yellow mutations at the mouse agouti locus. Obvious effects include hyperinsulinemia, obesity, stimulation of somatic growth and tumorigenesis, and coat color. Downstream influences of hyperinsulinemia and obesity on the individual's physiology determine important components of the obese yellow agouti mouse syndrome. Collectively, the phenotypic aberrations described support the concept that identical genomes are expressed in a spectrum of physiological phenotypes that reflect the complex interdependence of gene-regulated physiological pathways and processes in the organism throughout extended, but temporally ordered, periods of fetal and neonatal development and aging. This summary identifies important areas for additional research and provides integrated information required for a systematic approach to the development of interventions for common adult human health problems.

Agouti Signaling Protein↗
PubMed1999

Repeat exposure to incremental doses of acetaminophen provides protection against acetaminophen-induced lethality in mice: an explanation for high acetaminophen dosage in humans without hepatic injury.

In studies designed to simulate a clinical observation in which an individual became tolerant to normally lethal doses of acetaminophen (APAP), mice were pretreated with increasing doses of APAP for 8 days and challenged on day 9 with normally supralethal doses of APAP. These animals developed minimal hepatotoxicity after a challenge dose with a fourfold increase in LD50 to 1,350 mg/kg. The pretreatment regimen resulted in hepatic changes including: centrilobular localization of 3-(cysteine-S-yl)APAP protein adducts, selective down-regulation of cytochrome P4502E1 (CYP2E1) and CYP1A2 that produced the toxic metabolite, N-acetyl-p-benzoquinone imine, higher levels of reduced glutathione (GSH), centrilobular inflammation, and a fourfold increase in hepatocellular proliferation. The protection against the lethal APAP doses afforded by pretreatment is secondary to these changes and to the associated regional shift in the bioactivation of the APAP challenge dose from centrilobular to periportal regions where CYP2E1 is not found, protective GSH is more abundant, and where cell-proliferative responses are better able to sustain repair. This shift in APAP bioactivation results in less-intense covalent binding that is more diffuse and spread uniformly throughout the hepatic lobe, most likely contributing to protection by delaying the early onset of liver injury that has been generally associated with centrilobular localization of the adducts. Intervention of APAP pretreatment-induced cell division in mice with colchicine left them resistant to a 500-mg/kg (normally lethal) dose of APAP, but unable to survive a 1,000-mg/kg APAP challenge dose. The data demonstrate multiple mechanistic components to the protection afforded by APAP pretreatment. Whereas metabolic and physiological changes not dependent on cell proliferation are adequate to protect against 500 mg/kg APAP, these changes plus a potentiated cell-proliferative response are necessary for protection against the supralethal 1,000-mg/kg APAP dose. Furthermore, the data document an uncoupling of the traditional association between covalent binding and toxicity, and suggest that the assessment of toxicity following repeated or chronic APAP exposure must consider altered drug interactions and parameters besides those historically used to assess acute APAP overdose.

Acetaminophen↗
PubMed1999

Arctic and Antarctic exploration including the contributions of physicians and effects of disease in the polar regions.

A history of Arctic and Antarctic exploration, whether to find a Northwest Passage, North Pole, or South Pole, is a story of triumph and tribulation. The hardship experienced by polar explorers in the last 1000 years permeates the tales of achievement. Physicians and surgeons have played prominent roles in all major polar explorations. No significant Arctic voyage, particularly in the last 300 years, was made without a member of the party trained in the management of medical emergencies and in basic surgery. During times of health, surgeons functioned as the voyage naturalists with expertise in biology, botany, zoology, and the writing of scientific catalogs. Spurred by our interest and fascination with the history of polar exploration, we reviewed the roles of physicians and natural scientists in Arctic and Antarctic adventures.

Antarctic Regions↗
PubMed1999

Magnetic resonance imaging versus computed tomography for target localization in functional stereotactic neurosurgery.

OBJECTIVE: To determine whether magnetic resonance imaging (MRI), compared with computed tomography (CT), provides consistent and accurate target localization for ventrolateral thalamotomy and posteroventral pallidotomy. METHODS: For 93 procedures (78 pallidotomies and 15 thalamotomies) in 83 patients, coordinates for the anterior commissure, posterior commissure, and stereotactic target were calculated from MRI- and CT-derived images and compared. RESULTS: The mean differences for the target were -0.41 mm on the x axis (P < 0.001), 0.06 mm on the y axis (P = 0.412), and -0.34 mm on the z axis (P < 0.01). The mean absolute differences were 0.53 mm on the x axis (median, 0.50 mm; range, 0.00-2.00 mm), 0.46 mm on the y axis (median, 0.50 mm; range, 0.00-2.00 mm), and 0.78 mm on the z axis (median, 0.50 mm; range, 0.00-6.00 mm). The mean three-dimensional distance between MRI- and CT-derived coordinates for the anterior commissure was 1.65 mm, with a distance of more than 4 mm in two cases (2%). The mean three-dimensional distance for the posterior commissure was 1.65 mm, with a distance of more than 4 mm in two cases (2%). The mean three-dimensional distance for the target was 1.25 mm (median, 1.14 mm; range, 0.00-6.27 mm), with a distance of more than 4 mm in one case (1%). CONCLUSION: Statistically significant but relatively small differences between MRI- and CT-derived target coordinates were found. In some cases (approximately 2% of this series), the differences between MRI- and CT-derived coordinates may be relatively large (greater than 4 mm and up to 8 mm). However, given the superior anatomic resolution of MRI and the nature of the stereotactic procedures under consideration, we conclude that MRI, when validated within an institution, may be used alone for target localization in pallidotomy and thalamotomy.

Adult↗