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Biomedical subjects

D C Wright

Publications and source records attributed to D C Wright.

At least 55 records · Page 3Linked to original sources
PubMed1994

A protocol for measuring ophthalmologic morbidity and recovery after cranial base surgery.

Patients with cranial base tumors often have impairment in visual function, either due to the pathologic process itself or as a result of surgical treatment of the lesion. We conducted a pilot study in which we performed ophthalmologic evaluations on patients before and after cranial base surgery. The results of the study were used to develop a protocol and reporting form for longitudinal assessment of visual function in these patients. Use of the protocol and reporting form for the past 2(1/2) years has shown that they are easy for physicians to use and that the results provide a representative evaluation of the patient's ability to function visually in everyday life. The authors propose implementation of the protocol and reporting form as a means of collecting data for further research into visual function in patients with cranial base tumors.

Journal Article↗
PubMed1994

Pituitary carcinoma.

The presence of distant metastases may be asymptomatic in patients who present with symptoms and signs due to the local mass effects of an invasive pituitary adenoma. A case of pituitary carcinoma in a 54-year-old man who presented with widespread asymptomatic distant metastases 12 years after initial diagnosis is reviewed. The long course and asymptomatic metastases suggested a relatively slow-growing malignancy. The factors that played a role in the pathogenesis of the metastasis are unknown. A review of the literature on pituitary carcinoma suggests that accurate diagnosis and a multidisciplinary approach to management of such lesions emphasizing surgery, radiotherapy, and hormonal manipulation may provide these patients with the longest and best quality of survival.

Journal Article↗
PubMed1994

Identification and characterization of a monoclonal antibody that neutralizes ricin toxicity in vitro and in vivo.

We wanted to identify and characterize MAbs with specificity for the toxic lectin ricin, which could serve as detection reagents in elucidating mechanisms and tissue distribution. Neutralizing MAbs could be developed into immunotherapeutics to reverse clinical intoxications from immunotoxin or to counteract the use of ricin as a terrorist or biological warfare weapon. Two hybridomas, UNIVAX 70 and 138, producing MAbs against ricin were identified by Western blot strip analysis. The antibodies were IgG1 and were specific for the ricin A chain with no ricin B chain cross-reactivity. The MAbs neutralized ricin in vitro in an EL-4 mouse leukemia cell assay and in an in vivo mouse model. The two antibodies recognized the same epitope or overlapping epitopes, based on a competition with one another. All further characterization proceeded on the assumption that they were the same. The MAb UNIVAX 70/138 was characterized in vivo by titrating it against an 18 micrograms/kg (> six LD50) i.v. challenge and by titrating the i.v. toxin challenge against a constant dose of 100 micrograms of passive antibody per mouse. A 4:1 molar ratio of MAb to ricin led to neutralization of > or = 90% of the toxin in vitro. The MAb recognized ricin toxoid prepared by formaldehyde treatment and after conjugation of low molecular weight haptens (based on ELISA) equally as well as it recognized ricin and ricin A chain. The affinity and specificity of UNIVAX 70/138 give it excellent reagent potential, and the toxin-neutralizing capacity makes it at least a log and a half better than the next best candidate immunotherapeutic.

Animals↗
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↗
PubMed1994

Extreme lateral transcondylar approach: technical improvements and lessons learned.

An extreme lateral transcondylar or extreme lateral transfacetal surgical approach was used to treat 22 patients with complex lesions over a 22-month period. The lesions included basilar invagination with vertebral artery pathology, giant aneurysm or arteriovenous fistula of the vertebral artery, meningioma, chordoma, chondrosarcoma, and paraganglioma. The approach was used alone or in combination with a presigmoid petrosal or subtemporal-infratemporal approach. Refinements of the operative technique, treatment strategies for complex lesions, and the avoidance of complications are discussed. Complications included cerebrospinal fluid leakage, meningitis, pseudomeningocele, hemiparesis or quadriparesis, lower cranial nerve deficits, and vertebral artery injury requiring repair. With treatment, major neurological deficits resolved completely in three patients and partially in two. There was no operative mortality, but four patients died during the follow-up period. For the 18 surviving patients, the mean preoperative and postoperative Karnofsky scores were 81 and 93, respectively. For the four who died, the mean preoperative Karnofsky score was 73 and the mean postoperative score was 63.

Adolescent↗
PubMed1994

Surgical excision of meningiomas involving the clivus: preoperative and intraoperative features as predictors of postoperative functional deterioration.

Neurological deterioration is commonly seen after surgical excision of clival meningiomas; however, an understanding of the risk factors associated with postoperative deterioration can lead to improvements in outcome. In 75 patients with clival meningiomas operated on over a 7-year period, the following data were studied; preoperative variables such as presenting Karnofsky scale score, age, sex, and prior operations or radiation therapy. Radiological findings on magnetic resonance imaging or arteriography, such as the development of the arachnoidal cleavage plane between tumor and the brain stem, brainstem edema, tumor size, extent of compression on the brain stem, vascular encasement, and blood supply from the basilar artery were among other data studied. In addition, intraoperative findings such as development of the arachnoid plane, vascular encasement, and the difficulty of dissection were noted. Finally, each patient's neurological and functional statuses were recorded at 1 week postoperatively and at follow-up examinations. Early postoperative functional deterioration occurred in 45 patients (60%) and ranged from mild (30 patients) to severe (three patients). Significant improvement had occurred by the time of follow-up examination in all but four patients; however, permanent postoperative dysfunction was present in 12 patients. Statistical analysis revealed significant correlations between early functional deterioration and preoperative Karnofsky scale scores, male gender, radiological findings of the absence of an arachnoid plane, edema of the brain stem, and arteriographic supply from the basilar artery. Operative features included difficulty with dissection, an absent arachnoidal cleavage plane, and incomplete tumor resection. Permanent functional deterioration was statistically associated with the following: blood supply from the basilar artery, difficulty of dissection, incomplete tumor resection, and early postoperative dysfunction. Logistical regression analysis revealed that the most important risk factor for early postoperative deterioration was tumor size. Patients with large or giant tumors had a 6.7 to 13 times greater risk of functional deterioration, respectively, than patients with small- or medium-sized tumors. Excluding tumor size, the most important factor for permanent deterioration was blood supply from the basilar artery. Patients in this category had a 4.4 times greater risk of permanent functional deterioration. Three stages of tumor relationship to the brainstem arachnoid and pial membranes are proposed. Based on the results of this clinical study of clival meningiomas, suggestions are made for changes in the management strategy of these difficult lesions.

Adult↗
PubMed1994

Surgical resection of cranial base meningiomas.

This article outlines strategies for the surgical management of skull base meningiomas, including preoperative studies, general techniques of tumor resection, complications, postoperative management, follow-up, and nonsurgical modalities of treatment. The conventional and skull base surgical approaches are compared for meningiomas in specific skull base locations.

Cavernous Sinus↗
PubMed1993

Vein graft replacement of the middle cerebral artery after unsuccessful embolectomy: case report.

A forty-one-year-old man with a cavernous hemangioma of the right cavernous sinus underwent a preoperative cerebral angiogram and a balloon occlusion test of the internal carotid artery. During the operation to remove the cavernous sinus lesion, the ipsilateral electroencephalogram was found to be abnormal. An embolic occlusion of the M2 and M3 segments of the middle cerebral artery (MCA) was discovered. A platelet and thromboembolus was removed via multiple incisions, and flow was restored. The cavernous sinus lesion was removed uneventfully. At the end of the operation, the MCA was found to be reclotted. Flow was eventually restored by replacing the M2 segment of the MCA with a 2-cm saphenous vein graft. The patient recovered without any deficits of brain function and with transient deficits of Cranial Nerves III and VI. Computed tomography revealed infarcts in the temporal and parietal areas. When MCA embolectomy is unsuccessful, vein graft replacement should be considered to restore flow and to avoid major neurological deficits.

Adult↗
PubMed1993

Translabyrinthine approach to skull base tumors with hearing preservation.

The improvement in surgical techniques and the experience gained in treatment of skull base tumors have stimulated more aggressive management of larger lesions. Patients presenting with limited preoperative deficits have challenged the surgeon to design the surgical approach so as to minimize postoperative morbidity and preserve function. Tumors of the middle fossa and clivus with extension into the posterior fossa are usually approached by a combined subtemporal, transtentorial, transpetrous approach. In patients with preoperative hearing, the surgical exposure is often limited by the labyrinthine portion of the otic capsule. The technique of partial labyrinthectomy, removing the posterior and/or superior semicircular canals, maximizes exposure with preservation of hearing. This report details our experience with the partial labyrinthectomy approach for 14 patients with large skull base lesions. All patients had hearing preserved despite sacrifice of one or two of the semicircular canals. Bone pure-tone averages and speech discrimination scores were maintained near their preoperative levels. The indications, benefits, techniques, and hearing results of this approach are reviewed.

Adult↗
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↗