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Biomedical subjects

D C Wright

Publications and source records attributed to D C Wright.

At least 73 records · Page 4Linked to original sources
PubMed1990

Attenuation provided by four different audiometric earphone systems.

The attenuation provided by TDH earphones in MX-41/AR and P/N 51 cushions, Audiocup earphone enclosures and ER-3A insert earphones with ER3-14 foam earplugs was determined for 30 normally hearing subjects using a real-ear attenuation at threshold paradigm. The MX-41/AR and P/N 51 cushions provided about the same amount of attenuation which was less than the attenuation provided by the Audiocup enclosures. The ER-3A/ER3-14 provided the highest amount of attenuation. The MX-41/AR and ER-3A/ER3-14 attenuation values were in agreement with other studies using similar methodology. However, the attenuation provided by the Audiocup enclosures was considerably less, in the lower frequencies, than reported in two other studies. ANSI S3.1-1977 supra-aural earphone cushion attenuation values, which were determined using pure-tones presented in a free-field, should be replaced by earphone cushion attenuation values determined with 1/3 octave bands of noise presented in a diffuse sound field.

Adult↗
PubMed1990

Diphtheria toxin effects on brain-tumor xenografts. Implications for protein-based brain-tumor chemotherapy.

A model was developed to determine whether protein-based chemotherapeutic agents can cross the blood-brain barrier and successfully treat brain tumors. The human small-cell lung carcinoma N417D was grown as a solid tumor in the nude rat brain, and diphtheria toxin (DT) was administered intravenously as therapy. Because rat cells lack functional DT receptors and are 1000 to 10,000 times less sensitive to DT than human cells, a therapeutic window exists between the implanted human tumor and the nude rat host. The pharmacokinetic and pharmacodynamic characteristics of DT were defined. Within 6 hours, more than 90% of the initial DT concentration was removed from the blood. The blood-to-tumor transfer constant Ki for DT in small N417D tumors was 0.49 microliters/gm-min, one-fourth to one-fifth the reported values for permeability to proteins in other experimental tumor models. Despite the toxin's short plasma half-life and the relatively intact blood-tumor barrier, DT administered intravenously as a single dose significantly extended animal survival. Untreated nude rats developed solid parenchymal tumors and died in 11 to 16 days (median 15 days). When administered at 0.1 micrograms/animal, DT increased the median survival time to 19 days (p less than 0.0016) while 1.0-microgram doses extended median survival times to 26.5 days (p less than 0.0002). A higher dose of DT (3.0 micrograms) had no further beneficial effect on survival (26.1 days). Blood-brain barrier constraints to successful monoclonal antibody-based therapies of brain tumors may have been overestimated since antibody conjugates have plasma half-lives longer than DT, and the permeability of N417D tumors to DT is equal to or less than the permeability of other experimental tumors to large proteins. Recently developed immunotoxins that have the higher potency of DT and a therapeutic window as wide as DT has in this nude rat/human tumor paradigm may be effective in treating brain tumors despite limited blood-tumor permeability.

Animals↗
PubMed1989

Binding of [3H]inositoltrisphosphate and [3H]phorbol 12,13-dibutyrate in rat hippocampus following transient global ischemia: a quantitative autoradiographic study.

An in vitro quantitative autoradiographic binding study of the phosphatidylinositol system ligands [3H]inositol 1,4,5-trisphosphate (IP3) and [3H]phorbol 12,13-dibutyrate (PDBU) to rat brain slices was performed at 6, 12, 24, 28 and 72 h following a 20 min ischemic injury. PDBU binding showed a transient 20% decrease in the dentate gyrus and the CA3 the first 24 h as well as a 50% decrease in the CA1 at 72 h. A 50% decline in IP3 binding was seen in all regions at 6-12 h except the pyramidal cell layer of the CA1. This downregulation of calcium mobilizing intracellular receptors is probably a defence against ischemic neuronal cell death.

Animals↗
PubMed1989

Delayed c-fos proto-oncogene expression in the rat hippocampus induced by transient global cerebral ischemia: an in situ hybridization study.

The relative levels of c-fos mRNA in individual neurons of the hippocampal formation of rats is dramatically increased following 20 min of cerebral ischemia induced by 4-vessel occlusion. After 24 h of recirculation, a number of scattered neurons in the dentate hilus became hybridization positive. This effect appeared to peak between 24 and 48 h. A few neurons in the pyramidal cell layer of CA1 expressed c-fos as early as 24 h, but the most intense labeling in this region was seen at 72 h of recirculation. These results correlate well with the known distribution of delayed ischemic necrosis in the brain.

Animals↗
PubMed1989

Positron emission tomography in the detection of malignant degeneration of low-grade gliomas.

The management of low-grade gliomas represents a challenge to the physician as a significant proportion may undergo malignant degeneration to a high-grade tumor. We present the positron emission tomography (PET) scans, using [18F] fluorodeoxyglucose (FDG), of 12 patients who have histological and/or clinical evidence of malignant degeneration of a low-grade glioma. Each scan displays a focal area of hypermetabolism similar to that of malignant gliomas which arise de novo. Three patients also underwent PET scanning prior to malignant degeneration. When the initial scan is compared with the postmalignant degeneration study, a difference in tumoral glucose uptake can be recognized. A region previously shown to be hypometabolic develops focal hypermetabolism as malignant changes evolve. This study displays the utility of FDG-PET in the evaluation of malignant degeneration of low-grade gliomas. The knowledge that a neoplasm has altered its biological behavior may influence subsequent therapeutic options. If these findings can be confirmed in larger series and by other investigators, it is possible that FDG-PET may be adopted as one of the diagnostic tools for guiding the management of low-grade gliomas.

Adult↗
PubMed1988

The effect of unilateral and bilateral removal of the entorhinal cortex on the glucose utilization in various hippocampal regions in the rat.

In the present study lesion-induced changes in function of various hippocampal regions, as reflected by the metabolic rate of glucose, were measured by means of quantitative autoradiography, 4 days after unilateral or bilateral surgical removal of the entorhinal cortex. The greatest decrease (45%) was seen in the stratum lacunosum moleculare of the CA1, whereas a lesser decline (34%) was seen in the molecular layer of the dentate gyrus, stratum lucidum of the CA3 (31%) and the stratum radiatum of the CA1 (36%). These findings support the view that in addition to the indirect trisynaptic temporo-ammonic pathway, there is a functionally active direct pathway.

Animals↗
PubMed1988

Intravascular streaming and variable delivery to brain following carotid artery infusions in the Sprague-Dawley rat.

Intracarotid artery infusions in animals are commonly performed in studies of the blood-brain barrier and in chemotherapy trials. Implicit in the analysis of these experiments is that the infusate will be distributed to the territory of the internal carotid artery in a manner that is proportional to blood flow. Fifteen Sprague-Dawley rats were studied to determine if poor infusate mixing with blood due to intravascular streaming occurred during intracarotid artery drug infusions and if it could be eliminated with fast retrograde infusion. In three experimental groups, a radiolabeled flow tracer--14C-iodoantipyrine (IAP)--was infused retrograde through the external carotid artery into the common carotid artery at slow, medium, and fast rates (0.45, 1.5, and 5.0 ml/min). In a control group, IAP was injected intravenously (i.v.). Local isotope concentrations in the brain were determined by quantitative autoradiography, and the variability of isotope delivery was assessed in the frontoparietal cortex, temporal cortex, and caudate putamen of all animals. Streaming phenomena were manifest in all selected anatomic areas after the slow and medium rates of intraarterial infusion. After fast intracarotid infusion or i.v. injection, there was uniform distribution of isotope in the same brain regions.

Animals↗
PubMed1988

Meningeal carcinomatosis in the VX2 rabbit tumor model: detection with Gd-DTPA-enhanced MR imaging.

Meningeal carcinomatosis developed in 14 of 14 New Zealand White rabbits after infusion of a VX2 tumor cell suspension into the cisterna magna. All died or were killed 7-15 days after inoculation. Within days of the tumor infusion, magnetic resonance (MR) imaging with gadolinium-diethylenetriaminepentaacetic acid (DTPA) at 0.5 or 1.5 T demonstrated enhancement of the cerebrospinal fluid (CSF) secondary to disruption of the blood-CSF barrier by plaquelike lesions along the meninges. Eventually, meningeal enhancement was observed along the base of the brain and cervical spine. Quantitative assessment of the contrast enhancement on T1-weighted images revealed an increase in mean signal intensity of 213% +/- 130%. Contrast enhancement was not observed in four control animals who received an infusion of cell culture medium. These results demonstrate in an animal model that contrast material-enhanced MR imaging can be used to detect meningeal carcinomatosis by revealing breakdown of the blood-CSF barrier.

Animals↗
PubMed1988

Cerebral necrosis after radiotherapy and/or intraarterial chemotherapy for brain tumors: PET and neuropathologic studies.

Cerebral necrosis after radiotherapy for brain tumors is being recognized as a problem more common than previously estimated. Distinction between this iatrogenic complication and tumor recurrence cannot be made by either CT or MR imaging. By using positron emission tomography (PET) with 18F-deoxyglucose (FDG) we were able to reach a diagnosis of radiation necrosis, later verified, in 10 of 95 patients referred for the purpose of differentiating tumor recurrence from necrosis. The critical PET-FDG feature was focal hypometabolism in the area of necrosis, which contrasted with the hypermetabolism associated with the residual/recurrent tumor. In addition, four cases of cerebral necrosis after supraophthalmic, intraarterial chemotherapy (BCNU) were studied with the PET-FDG method. The area of chemotherapy damage was also characterized by marked hypometabolism. Histology revealed both similarities and differences between radio- and chemonecrosis.

Adolescent↗
PubMed1988

MR imaging of primary tumors of trigeminal nerve and Meckel's cave.

MR imaging features of 11 primary tumors of the trigeminal nerve and Meckel's cave were analyzed. The tumors consisted of two trigeminal schwannomas, five meningiomas, one lipoma, and three epidermoid tumors. The trigeminal schwannomas had homogeneously decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images. Three of the five meningiomas had signal intensity similar to that of surrounding brain on both T1- and T2-weighted images. One meningioma had decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images. The other had relatively low signal intensity on both T1- and T2-weighted images owing to heavy calcification demonstrated on CT. The lipoma had homogeneous signal intensity that was isointense with orbital and subcutaneous fat on both T1- and T2-weighted images. The epidermoid tumors had decreased signal intensity on T1-weighted images and markedly increased signal intensity on T2-weighted images. In addition, the epidermoids had an insinuating growth pattern and minimal mass effect. The extent of involvement in the trigeminal nerve distribution was well demonstrated in each case. Because of its multiplanar capability, exquisite anatomic detail, and characteristic tissue signal intensity, we conclude that MR is helpful in the differential diagnosis of primary tumors of the trigeminal nerve and Meckel's cave and in the evaluation of tumor involvement for preoperative planning.

Adolescent↗
PubMed1987

Chronic vaginal candidiasis in women with human immunodeficiency virus infection.

Twenty-four percent (7/29) of human immunodeficiency virus-infected women seen at Walter Reed Army Medical Center between 1983 and 1986 presented with a history of chronic refractory vaginal candidiasis. In addition to vaginal candidiasis, all patients were found to have oral thrush on physical examination, severe T-helper cell depletion (mean T-helper cell count of 90), and markedly decreased T4/T8 ratios (mean, 0.3); six of seven women were anergic by delayed-type hypersensitivity skin testing. The conditions of six (86%) of these seven women have progressed to acquired immunodeficiency syndrome (WR6 classification). Chronic refractory vaginal candidiasis may be a presenting symptom of human immunodeficiency virus infection. Women with human immunodeficiency virus infection and unexplained oral and vaginal candidiasis are at high risk to develop other opportunistic infections.

Acquired Immunodeficiency Syndrome↗
PubMed1987

The NCI-atlas of dose distributions for regular 125I brain implants.

In connection with the development of an optimization method for 125I brain implants in irregularly shaped target volumes, a systematic study was conducted toward optimizing seed configurations for regular target volumes. The intention was to find basic rules for the positioning of strings of seeds in the cylindrical implant pattern of the stereotactic neurosurgical procedure in use, and in accordance with the following criteria: (i) steep dose fall-off outside the target volume; (ii) coverage of the target volume by making the prescribed dose surface coincident with the target volume surface within 1 mm; (iii) uniformity of the dose distribution in the target volume as far as achievable with a seed implant. As a result of this study, an atlas of optimized regular 125I brain implant configurations was compiled. Regular implants were understood as being cylindrical or spherical. Diameters and heights from 2 to 5 cm were covered.

Brachytherapy↗
PubMed1987

Effect of barbiturate coma on glucose utilization in normal brain versus gliomas. Positron emission tomography studies.

Glucose utilization by normal and neoplastic cerebral tissue can be measured in humans using positron emission tomography (PET) with fluorine-18-labeled 2-deoxy-D-glucose (FDG). Malignant gliomas are known to exhibit hypermetabolic glucose consumption compared to normal brain. Barbiturate-sensitive cerebral glucose utilization is coupled to neuronal activity, and lesions lacking neuronal activity should be relatively insensitive to barbiturate suppression of glucose utilization. In a study to examine this phenomenon, three patients with cerebral gliomas underwent FDG-PET while awake and during deep barbiturate coma. Cerebral glucose utilization was measured in normal brain, tumor, and a homologous, non-neoplastic control site in the contralateral hemisphere. A glucose utilization ratio for tumor/control tissue was calculated. The mean reduction of glucose utilization during barbiturate coma was: gray matter 67%, white matter 47%, basal ganglia 66%, thalamus 57%, cerebellar cortex 55%, tumor 32%, and the contralateral control site 64%. The mean tumor glucose utilization ratio was 1.48:1 in the awake state and 2.69:1 during barbiturate coma. The changes in gray matter, basal ganglia, thalamus, cerebellar cortex, and tumor/control tissue ratio were significant (p less than 0.05). In one patient, deep tumor invasion not evident on computerized tomography, magnetic resonance imaging, or baseline FDG-PET was apparent during barbiturate-enhanced FDG-PET scanning. The study findings suggest that gliomas resist suppression of glucose utilization by barbiturates; this supports the hypothesis that barbiturates reduce neuronal metabolism by blocking synaptic activity. This differential effect on normal brain and gliomas enhances the capability to assess the extent of neoplastic tissue in brain and may represent the basis for novel therapeutic strategies.

Adult↗
PubMed1987

The effect of 125I interstitial radiotherapy on blood-brain barrier function in normal canine brain.

Blood-brain barrier (BBB) function was studied in 14 normal dogs at time periods from 7 to 717 days after permanent insertion of 5- to 7-mCi seeds of iodine-125 (125I) for interstitial radiation. The BBB function was measured with carbon-14-labeled alpha aminoisobutyric acid (AIB) and quantitative autoradiography, and expressed as a unidirectional blood-to-brain transfer constant, K. The 125I radiation lesions consisted of three concentric histologically and functionally distinct zones: 1) a central zone of calcified necrosis; 2) a spongy fluid-filled zone; and 3) a narrow rim (2.6 +/- 0.6 mm wide) of viable brain tissue with increased permeability. Within this rim, the mean value of the K of AIB was 5.8 times that of normal cortex. Over the 7- to 392-day time period the value of K remained rather constant, and by 716 days K values had returned to normal. There was moderate regional variation in the value of K; it was highest in the white matter and lowest in the gray matter surrounding the radiation lesion. The radiation lesion progressively increased in size from 7 to 80 days, after which there was little change. This study illustrates that the geographically circumscribed radiation from 125I seeds is accompanied by similarly well-defined changes in BBB function, which may persist for over 1 year following insertion of the 125I seed. This altered BBB function is probably responsible for the cerebral edema associated with 125I interstitial radiotherapy.

Aminoisobutyric Acids↗
PubMed1986

Role of lipopolysaccharide and capsule in the serum resistance of bacteremic strains of Escherichia coli.

To define the relative roles of capsule and lipopolysaccharide in the virulence of Escherichia coli obtained from blood, we compared the behavior of K1- and K5-encapsulated strains in serum bactericidal and rat virulence assays. Unencapsulated isogenic mutants selected from five parent strains of E. coli O12:K1, but not of O18:K1 or O7:K1 (all rough-specific phage insensitive), were lysed by normal human sera. In contrast, isogenic mutants from strains of serotypes O6:K5 and O18:K5 retained the serum resistance of the parent strains. There was a greater than 10(5) difference in LD50 in newborn rats between K1-positive and K1-negative pairs of E. coli serotypes O18 and O7 and a greater than 1 log difference between isogenic pairs of serotype O12; however, the K5 isogenic pairs had a similar LD50. Some non-O6 O serotypes, however, required the K5 capsule for serum resistance. We conclude that some O serotypes require encapsulation for optimal virulence but that other O serotypes may not.

Animals↗