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Biomedical subjects

D C Wright

Publications and source records attributed to D C Wright.

At least 19 recordsLinked to original sources
PubMed1995

Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60 patients.

The management of chordomas and chondrosarcomas involving the cranial base remains controversial. The options for therapy include biopsy, partial resection, radical resection, and various forms of radiotherapy. In this article, we analyze the outcome of 60 patients with cranial base chordoma or chondrosarcoma treated with extensive surgical resection between 1984 and 1993. Forty-six patients had chordomas, and 14 had low-grade chondrosarcomas; 50% of these patients had been treated previously. Preoperative studies included computed tomography, magnetic resonance imaging, cerebral angiography, and balloon occlusion test of the internal carotid artery, as indicated. Magnetic resonance imaging was performed on all patients during follow-up. The surgical approaches used for tumor resection were predominantly the following: subtemporal, transzygomatic, transcavernous, and transpetrous apex; subtemporal and infratemporal; extended frontal; and extreme lateral transcondylar. Staged operations with a combination of approaches were used when necessary (52% of cases) to remove a tumor more completely. Statistical analysis was done by the chi 2 test and correlation matrix. Sixty-seven percent of the patients had total or near-total resection. Twenty percent of the patients received postoperative radiotherapy. Eleven patients died during the postoperative follow-up period, nine with chordomas and two with chondrosarcomas. Three patients died because of systemic complications within 3 months after surgery, five died because of tumor recurrence, one died from unrelated causes, and two died from late complications of radiotherapy. The recurrence-free survival rate for all tumors was 80% at 3 years and 76% at 5 years. Chondrosarcomas had a better prognosis than chordomas (recurrence-free survival rates, 90% at 5 years and 65% at 5 years, respectively; P = 0.09). Patients who had undergone previous surgery had a greater risk of recurrence (5-year recurrence-free survival rate, 64%) than did patients who had not undergone previous surgery (5-year recurrence-free survival rate, 93%; P < 0.05). Patients with total or near-total resection had a better 5-year recurrence-free survival rate (84%) than did patients with partial or subtotal resection (64%) (P < 0.05). Postoperative leakage of cerebrospinal fluid was the most frequent complication (30% of patients) and was found to increase the risk of permanent disability. Patients who had undergone previous radiotherapy had a greater risk of death in the postoperative period (within 3 months of their operations) and during follow-up. However, total or near-total resection did not increase the rate of postoperative disability.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1994

Immunogenic and antigenic properties of a heptavalent high-molecular-weight O-polysaccharide vaccine derived from Pseudomonas aeruginosa.

We investigated the chemical and immunologic properties of a heptavalent vaccine composed of high-molecular-weight polymers of the lipopolysaccharide (LPS) O polysaccharides representative of the most common clinical isolates of Pseudomonas aeruginosa. We also evaluated the serum antibody response to nonvaccine strains of P. aeruginosa, including strains expressing structural variants (subtype strains) of the O side chain of the vaccine strains. The polyvalent vaccine, prepared under conditions suitable for human use, contained low levels of contaminants and passed preclinical safety and toxicity tests required for human use. Chemical analyses indicated that individual polysaccharides were composed of both O-side chain and core sugars. Following immunization of C3H/HeN mice and New Zealand White rabbits, antibody titers against vaccine components increased between 32- and 200-fold. Antibodies reactive with LPS isolated from smooth and rough nonvaccine strains were also elicited. Analysis of the opsonic activity against the known LPS subtype variants of the vaccine strains revealed a variable pattern of killing, which ranged from opsonic killing of > or = 69% of bacterial cells representing all subtype variants within a serogroup to opsonization of only a minority of the subtype variant strains. Mouse and rabbit immune sera showed different patterns of opsonic activity against subtype strains, indicating that different epitopes on these antigens are immunodominant in the representatives of these two animal species tested. The polyvalent vaccine was effective at eliciting antibodies to vaccine components in mice and rabbits, but it remains to be determined if the current heptavalent formulation contains sufficient components to provoke human antibodies reactive with a majority of clinical strains of P. aeruginosa.

Animals↗
PubMed1994

Cranial base approaches to intracranial aneurysms in the subarachnoid space.

The use of cranial base approaches to aneurysm surgery is illustrated by means of patient examples. Over a 9-year period, cranial base approaches were used to expose and treat 38 aneurysms involving the anterior communicating artery complex, proximal internal carotid artery, basilar artery, or vertebral artery. The approaches included orbital osteotomy, orbitozygomatic osteotomy, petrous apicectomy, presigmoid petrosectomy, and extreme lateral transcondylar methods. Complications related to the approaches included one partial ptosis and two cerebrospinal fluid leaks, which resolved with treatment. The technique of three-dimensional computed tomographic angiography was useful in delineating the vascular anatomy and its relation to the cranial base structures. This helped the surgeon plan the appropriate approach to the aneurysm. Cranial base approaches, used selectively, can provide improved exposure of deep-seated aneurysms and large or giant aneurysms, while minimizing brain retraction.

Aneurysm, Ruptured↗
PubMed1992

Attenuation values for a supra-aural earphone for children and insert earphone for children and adults.

Earphone attenuation values were determined for 17 children (6-14 years old) using supra-aural (TDH-49P/Model 51 cushion) and insert earphones (E-A-Rtone 3A) terminated by an E-A-Rlink 3A (for normal size ear canals) or E-A-Rlink 3B (for small size ear canals) foam eartips, and for 10 adults having small ear canals using insert earphones and E-A-Rlink 3B foam eartips. The test signals were 1/3-octave bands of noise presented in a diffuse sound field (re: ANSI S12.6-1984). The supra-aural earphone attenuation values for the children were slightly higher (more attenuation) or similar to reported adult values, and always lower (less attenuation) compared with insert earphone/E-A-Rlink 3A (IE/3A) or 3B (IE/3B) values for both children and adults. The IE/3B attenuation values were similar between the children and adults and provided slightly more attenuation than the IE/3A. Overall, the results indicated that the ANSI S3.1-1991 maximum permissible ambient noise levels allowed in a test room for ears covered testing with a supra-aural earphone, which were determined using adult values, are appropriate for testing children. Future revisions of ANSI S3.1-1991 may include maximum permissible ambient noise levels for testing with insert earphones. The IE/3A and IE/3B attenuation values could be used for that purpose. In the meantime, because more attenuation was provided by the IE/3A and IE/3B, they can be used for testing both children and adults in higher ambient noise levels than specified in ANSI S3.1-1991.

Acoustic Stimulation↗
PubMed1992

Mice are actively immunized after passive monoclonal antibody prophylaxis and ricin toxin challenge.

Mice passively immunized by a protective, anti-ricin A-chain monoclonal antibody, then challenged intravenously with ricin, were protected from a subsequent ricin challenge, and were actively immunized. Two significant advantages accrued from this experiment: the monoclonal antibody neutralized the toxicity of the ricin immunogen, and active immunization was achieved with very low antigen load (approximately 0.5 microgram/mouse). We ruled out the possibility that residual monoclonal antibody provided the protection by using three independent criteria. There was significant (four orders of magnitude) enhancement of the immune response in the presence of the monoclonal antibody; control immunizations of mice with ricin A-chain, ricin B-chain or either chain with the monoclonal antibody did not induce active immunity; and the active immunization could not be replicated when protective goat polyclonal antibody was substituted for the monoclonal antibody. Because high titres were achieved rapidly without any adjuvant, we are currently investigating haptenized ricin to determine if anti-hapten monoclonal antibodies can be produced by this refined procedure.

Animals↗
PubMed1991

Protection against tetrodotoxin and saxitoxin intoxication by a cross-protective rabbit anti-tetrodotoxin antiserum.

A tetrodotoxin-formaldehyde-keyhole limpet hemocyanin conjugate was used to immunize a rabbit for the production of anti-toxin antiserum. The antiserum cross-reacted against both tetrodotoxin (TTX) and saxitoxin (STX), and in a quantitative in vitro assay was able to protect cells in a dose-dependent manner from the effects of either TTX or STX. The antiserum was also able to passively protect mice challenged in vivo with either toxin. Hybridomas producing monoclonal antibodies against toxin were obtained from the spleens of mice immunized with the same conjugate.

Animals↗
PubMed1991

Naloxone eliminates passive avoidance retention deficits produced by pretest exposure to novelty in rats.

Pretest exposure to novelty or injections of beta-endorphin can enhance passive avoidance (PA) retention (e.g., Izquierdo & McGaugh, 1985). Enhanced retention may result from a "state-dependent" match between the CNS state during test and the novelty-induced beta-endorphin state that is obtained during training in a novel apparatus. Our Experiment 1 suggests that, unlike PA, Pavlovian fear conditioning in a conditioned lick suppression (CLS) paradigm may be beta-endorphin "state-independent." Rats were given one tone-shock pairing in a novel environment. Baseline lick rates and CLS tested 48 h later in a familiar environment were not affected by pretest exposure to novelty and/or injections of 3.33 mg/kg naloxone HCl. In Experiment 2, the same rats were PA trained/tested in a new apparatus. Saline or naloxone injections and various exposure (novel, familiar, none) conditions preceded (1h) the 24-h retention test. Pretest exposure to novelty reduced retention and naloxone eliminated that deficit. In Experiment 3, naive rats given pretest exposure to novelty also showed a PA retention deficit. The results of Experiments 2 and 3 may complement rather than contradict previous findings. Pretest induction of a beta-endorphin state by novelty may either enhance state-dependent retrieval of a "weak" memory trace or make a "strong/well consolidated" training memory more vulnerable to retroactive interference from "new learning" during the pretest exposure period.

Animals↗
PubMed1991

Intravascular streaming during carotid artery infusions. Demonstration in humans and reduction using diastole-phased pulsatile administration.

Intra-arterial carotid artery chemotherapy for malignant gliomas is limited by focal injuries to the eye and brain which may be caused by poor mixing of the drug with blood at the infusion site. This inadequate mixing can be eliminated in animal models with diastole-phased pulsatile infusion (DPPI) which creates 1-ml/sec spurts during the slow blood flow phase of diastole. Before treatment with intracarotid cisplatin, 10 patients with malignant gliomas were studied to determine whether intravascular streaming occurs after intracarotid infusion in humans, and if so, if it is reduced with DPPI. Regional cerebral blood flow (rCBF) studies were performed by intravenous injection of H2(15)O and positron emission tomography. This was followed by supra- or infraophthalmic internal carotid artery (ICA) injections of H2(15)O with either continuous infusion or DPPI. Local H2(15)O concentration in the brain was determined and the images of radiotracer distribution in the continuous infusion and DPPI studies were compared to the rCBF images. Intravascular streaming of the infusate was identified by a heterogeneous distribution of the infused H2(15)O in brain compared to rCBF. Extensive and variable intravascular streaming occurred in three patients who received infusions into the supraophthalmic segment of the ICA. Some brain areas received up to 11 times the expected radiotracer delivery, while other regions received as little as one-tenth. This streaming pattern was markedly reduced or eliminated by DPPI. In the five patients who received infraophthalmic infusions, a minimally heterogeneous distribution of the infusate was detected. The authors conclude that extensive intravascular streaming accompanies supraophthalmic ICA infusions in patients. The magnitude of streaming can be substantially reduced or eliminated with DPPI. Those who perform intra-arterial infusion should consider using DPPI to assure uniform drug delivery to brain.

Analysis of Variance↗
PubMed1991

Safety and immunogenicity of multiple conventional immunizations administered during early HIV infection.

Twenty-one asymptomatic adults who had recently received multiple polysaccharide, live viral, and protein-derived vaccines were identified as being infected with human immunodeficiency virus (HIV). The mean subject age was 24 years (range 18-33); 20 of 21 (95%) were male. The mean T4 count was 523/mm3 with a mean T4/T8 ratio of 0.6. Serologic responses to immunization with meningococcus group C, adenovirus types 4 and 7, tetanus, and diphtheria were evaluated for the HIV seropositive subjects and were compared with the responses of similarly vaccinated age-, sex-, and race-matched HIV-seronegative controls. Significantly fewer (p less than 0.03) HIV subjects responded to meningococcus C (bactericidal antibody) and adenovirus 4 (neutralizing antibody) vaccines than did normals; the HIV-infected subjects who did respond produced functional antibody comparable to that of normals. Booster responses of HIV subjects to tetanus and diphtheria were comparable to those of normals. HIV-infected vaccine nonresponders did not differ from HIV-infected responders in total white blood cell, T4, T4/T8, total serum IgG, or delayed-type hypersensitivity skin test reactivity. All HIV subjects had negative cultures for live vaccine viruses (rubella, measles, adenovirus, and poliovirus). Postimmunization, no clinically apparent adverse reactions to vaccination were detected.

Adult↗
PubMed1990

Postischemic glucose metabolism is modified in the hippocampal CA1 region depleted of excitatory input or pyramidal cells.

During early postischemic reperfusion, the vulnerable brain regions (e.g., hippocampal CA1) show a relatively high deoxyglucose accumulation. To investigate if this accumulation is a marker for the later-occurring regional cell death and to determine its cellular localization, we studied the glucose metabolism in the CA1 region post ischemia after removal of its pre- or postsynaptic components. A 20-min period of cerebral ischemia was used for selective removal of the main postsynaptic component in CA1 pyramidal cells, and a bilateral intraventricular injection of kainic acid for removal of the majority of presynaptic axon terminals in this region (and postsynaptic terminals and cell bodies in CA3). The glucose metabolism was studied in these two lesion types and in sham-operated animals before and after a period of ischemia. There was a 60% reduction of metabolism after ischemia in the nonvulnerable regions, whereas CA1 and sometimes CA3 showed a columnar pattern of high and low metabolism. CA1 and CA3 devoid of the postsynaptic component showed increased postischemic metabolism. The latter was due to the presence of macrophages, as demonstrated by an enzyme histochemical stain for nonspecific esterase. CA1 with no presynaptic component showed a postischemic depression of the glucose metabolism similar to the rest of the brain. It is suggested that the level of the postischemic glucose metabolism in the ischemia-vulnerable regions is determined by the presence of both synaptic components. The presence of macrophages in a region gives rise to apparently normal values of glucose metabolism.

3-O-Methylglucose↗
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↗