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Biomedical subjects

B Copeland

Publications and source records attributed to B Copeland.

At least 19 recordsLinked to original sources

DNA scission after focal brain ischemia. Temporal differences in two species.

BACKGROUND AND PURPOSE: Species- and model-dependent differences in cell response to focal brain ischemia may underlie differences in adhesion receptor expression. The aim of this study was to quantitatively evaluate the spatial and temporal distribution of dUTP incorporation into damaged DNA, as an indicator of ischemic injury, in the corpus striatum. METHODS: Cerebral ischemia was produced in 16 nonhuman primates and 19 rats by occluding the middle cerebral artery (MCA:O) with reperfusion for various periods. In situ dUTP was incorporated into cells with DNA damage by terminal deoxynucleotidyl transferase (TdT), DNA polymerase I, or the Klenow fragment of DNA polymerase. Dual immunolabeling experiments with immunoprobes against neuronal, vascular, or glial marker proteins were performed. RESULTS: Significant topographical differences in dUTP between the two species were seen. In both models the TdT and polymerase I regions changed characteristically during focal ischemia. The number and density of dUTP-labeled cells increased with time from MCA:O and were dramatically different between the species (2P < .001). By 2 hours of ischemia, the density of dUTP label was 48.8 +/- 10.3 cells/mm2 in the primate and 2.4 +/- 0.8 cells/mm2 in the rat (2P < .05), but these values became nearly identical by 24 hours of reperfusion. In the primate, 80.0 +/- 6.6% of labeled cells displayed microtubule-associated protein-2 antigen (at 2-hour MCA:O), while 1.8 +/- 0.5% were associated with microvessels at 24 hours of reperfusion. CONCLUSIONS: In situ detection of DNA damage, accomplished by three methods, reveals distinct temporal, topographical, and density differences in ischemic injury to cells in the primate and the rat corpus striatum as a result of MCA:O.

Animals↗

Cerebral aneurysm thrombosis, shrinkage, then disappearance after subarachnoid hemorrhage.

The case is presented of a 37-year-old man with spontaneous thrombosis of a 10-mm left posterior communicating artery aneurysm, following presumed subarachnoid hemorrhage with negative angiography. Sequential magnetic resonance angiography and magnetic resonance source imaging (at 2 weeks, 3 months, 2 years, and 2 years, 5 months) showed progressive shrinkage and disappearance of the aneurysm.

Adult↗

A technique for interactive image-guided neurosurgical intervention in primary brain tumors.

Interactive image-guided neurosurgical techniques allow safer and more complete cytoreduction of gliomas. This is most significant for low-grade tumors, whose configurations and margins are perhaps better appreciated by reference to registered MR images rather than by reliance on direct visualization using microscopic illumination. Spatially registered electro-physiologic recordings of intraoperative cortical stimulation to map language and motor function can increase the margin of safety for performing radical resections. By individualizing approaches and optimizing results, these technologies promise a new degree of standardization of outcome after resective surgery for all glial tumors.

Brain Mapping↗

Prolactin-secreting pituitary carcinoma with implants in the cheek pouch and metastases to the ovaries. A case report and literature review.

BACKGROUND: Prolactin-secreting pituitary carcinomas are uncommon, locally destructive neoplasms that rarely metastasize outside the central nervous system. The authors report a case of a prolactin-secreting tumor that initially presented as the empty sella syndrome. Two recurrences along transsphenoidal surgery tracts in cheek pouches were followed by distant metastases later in the abdomen and pelvis. Only 10 previous cases of either extracranial or intracranial metastases from prolactin-secreting pituitary carcinomas have been reported. No metastases below the diaphragm have been reported previously. METHODS: The patient's cheek pouch implants, lymph node metastases, ovarian metastases, and uterine metastases were studied with prolactin-specific immunohistochemistry. RESULTS: Long term treatment with bromocriptine, several debulking surgeries, extensive local radiation therapy (external beam and proton beam), and cytotoxic chemotherapy had little impact. Tamoxifen, however, may have slowed tumor growth. CONCLUSION: Tamoxifen may have efficacy in the treatment of prolactin-secreting pituitary carcinomas.

Adult↗

X-ray absorption spectroscopy comparison of the active site structures of Phanerochaete chrysosporium lignin peroxidase isoenzymes H2, H3, H4, H5, H8, and H10.

The iron heme and its immediate environment can provide information that is pivotal to our understanding of the structural and mechanistic features that confer unusual properties to the heme peroxidases. X-ray absorption spectroscopy (XAS), which is ideally suited for the investigation of the local environment and electronic structure of the heme iron of hemeproteins, has been used to characterize a variety of lignin peroxidase and manganese-dependent peroxidase isoenzymes produced by the white rot fungus Phanerochaete chrysosporium. The data suggest no differences within the error in the first coordination shell of iron for the isoenzymes H2, H3, H4, H5, H8, and H10 examined in this study. The pyrrole nitrogens are at a distance of 2.05 +/- 0.015 A, and the proximal histidine nitrogens are at 1.93 +/- 0.02 A, while the sixth ligands are located at 2.17 +/- 0.03 A. Significant differences are observed in higher coordination shells which may be related to conformational differences in the heme.

Binding Sites↗

Presurgical localization of functional cortex using magnetic source imaging.

The boundaries of somatosensory cortex were localized noninvasively by means of a large-array biomagnetometer in six patients with mass lesions in or near eloquent cortex. The results were used by neurosurgeons and neurologists in preoperative planning and for reference in the operating room. The magnetic source imaging (MSI) localizations from somatosensory evoked potentials were used to predict the pattern of phase reversals measurable intraoperatively on the cortical surface, providing a quantitative comparison between the two measures. The magnetic localizations were found to be predictive in all six cases, with the two sets of localizations falling within an 8-mm distance on average. Somatosensory localizations using MSI offer accuracy in localizing somatosensory cortex stereotactically and in depicting its relationship to lesions. Such data are valuable preoperatively in assessing the risks associated with a proposed surgical procedure and for optimizing subsequent minimum-risk surgical strategy.

Adult↗

Neurological sequelae of the operation "baby lift" airplane disaster.

The aircraft disaster of the first flight of Operation "Baby Lift", which departed from Saigon, Vietnam, April 4, 1975, was survived by 149 orphaned children on their way to adoptive homes in the West. It had 157 passenger fatalities. The aircraft disaster exposed the surviving children to a complex disaster environment in which subatmospheric decompression, hypoxia, and deceleration were experienced, many children suffered a transient unconsciousness. We examined 135 surviving children between 1978 and 1985. The U.S. resident children were examined in the years 1979 to 1982 at an average age of 8 years and 6 months. They displayed the following symptomatology: attention deficit (> 75%), hyperactivity (> 65%), impulse disorder (> 55%), learning disabilities (> 35%), speech and language pathology (> 70%), and soft neurological signs (> 75%). The European children were examined in the years 1983 to 1985. On arrival at the adoptive home, 2 weeks after the accident they displayed the following symptomatology: muscle hypotonia (26%), seizures (2.5%), and regressed developmental milestones (33%). At the time of the diagnostic evaluations (1983 to 1985) the average age was 11 years and 8 months. They displayed the following symptomatology: attention deficit (59%), hyperactivity (52%), impulse disorder (48%), learning disabilities (43%), soft neurological signs (43%), epilepsy (16%), and speech and language pathology (34%). We conclude that a complex disaster environment can cause brain damage in children without prolonged unconsciousness, and that victims of disasters require a thorough evaluation from a multidisciplinary team.

Accidents, Aviation↗

2-Chlorodeoxyadenosine dose escalation in nonhematologic malignancies.

PURPOSE: We performed a dose-escalation study of 2-chlorodeoxyadenosine (2-CdA) in solid tumors to determine the maximum-tolerated dose (MTD) and define its toxicity profile at higher doses. PATIENTS AND METHODS: Twenty-one patients, seven with malignant astrocytoma, twelve with metastatic melanoma, and two with metastatic hypernephroma, were enrolled onto the study. Patients were entered onto cohorts that received 0.10, 0.15, or 0.20 mg/kg/d of 2-CdA by continuous intravenous infusion for 7 days every 28 days. 2-CdA levels were determined by radioimmunoassay. In tumor tissue samples, deoxycytidine kinase (dCK) levels were measured by both enzyme activity and immunoreactive protein analysis. RESULTS: Of seven patients treated with 2-CdA at 0.1 mg/kg/d, one experienced grade 3 or 4 myelotoxicity. Of 11 patients treated at 0.15 mg/kg/d, four experienced myelotoxicity, two after a single course of 2-CdA. All three patients who received 2-CdA at 0.2 mg/kg/d experienced myelosuppression. Neurologic events occurred in two patients, both with malignant melanoma. Two of seven patients (28.6%) with astrocytomas obtained partial responses with a median duration of 8 months. 2-CdA penetrated the blood-brain barrier. An association was found between dCK levels as measured by enzymatic activity and immunoreactive proteins, but this did not correlate with 2-CdA tumor responsiveness. CONCLUSION: The MTD for 2-CdA delivered as a 7-day intravenous infusion in patients with nonhematologic malignancies was determined to be 0.1 mg/kg/d, the same as the MTD for patients with hematologic malignancies. There was no clinical correlation with dCK expression and response to 2-CdA. The responses noted in patients with malignant astrocytoma warrant further phase II study.

Adult↗

Noninvasive presurgical neuromagnetic mapping of somatosensory cortex.

Rapid presurgical neuromagnetic localization of the somatosensory cortex was performed successfully on five patients with a large-array biomagnetometer by a protocol called magnetic source imaging (MSI). Determination of the location of the central sulcus is important in assessing operative risk and determining the optimal operative approach to structural lesions in the vicinity of the motor strip. The use of magnetic resonance imaging anatomical methods and intraoperative visual identification can be imprecise, whereas invasive localization prolongs operative time, adds cost, and entails added risk. Until the recent development of large-array biomagnetometer systems, neuromagnetic localization of the central sulcus had been demonstrated in research but was so time consuming and laborious as to preclude routine clinical use. In this study, the validity of MSI localizations was confirmed intraoperatively by direct cortical recording of somatosensory evoked potentials and/or direct motor stimulation. Complete agreement was found between MSI and intraoperative mapping in locating the central sulcus. Objective confirmations considered together with the speed and reliability of the procedure and with the presurgical availability of the results suggests the potential utility of MSI for routine surgical planning.

Adult↗

Percutaneous injection of glycerol for the treatment of trigeminal neuralgia.

There continues a significant debate over the best contemporary method for treating trigeminal neuralgia. Glycerol injection into the trigeminal cistern has been used in a consecutive series of 200 patients. A total of 80% of the patients have had good or excellent pain relief. Side effects have been a mild and usually transient numbness and tingling or mild objective sensory deficit to pin and touch in approximately 1/2 of the patients. Complications have been extremely infrequent and have resolved in time. A recurrence rate of 24% has been the single largest disadvantage of the procedure. Reinjection is usually successful in treatment of recurrence. The combination of efficacy, minimal and temporary neurologic dysfunction, and low complication rate make this procedure, in our opinion, the procedure of choice for the first step, when surgical treatment is required.

Female↗

Massive preoperative pulmonary embolism and suprasellar brain tumor: case report and review of the literature.

A 57-year-old man presented to our facility with the diagnosis of a suprasellar mass and died on the 2nd post-admission day from a massive pulmonary embolism. At autopsy, the mass was diagnosed as craniopharyngioma. This case report and review of the literature suggest an intimate relation between brain tumors and thromboembolic complications as evidenced by the high incidence of this association, the frequent occurrence of coagulopathies in patients with brain tumors, and the prevalence of tumors in the suprasellar location. The specific mechanisms that may be at play are reviewed.

Brain Neoplasms↗

Seizures during the immediate postoperative period.

Twenty-three of 538 patients undergoing elective craniotomy had a seizure within 24 hours after operation. The lesion had been located extra-axially in 15 patients and intra-axially in 8 patients. Except for 1 patient who had a parietal craniotomy for an arteriovenous malformation, all patients had a frontal or temporal exposure. Only 5 patients had a previous history of seizures. Adequate levels of anticonvulsant medication were not present in 19 of the 23 patients before operation. No major postoperative metabolic abnormalities were noted in any of the 23 patients. Thirteen of the 23 patients underwent computed tomography to evaluate the etiology of their seizures; none had a significant intracerebral or extracerebral hematoma. This review suggests that an early postoperative seizure is unlikely to be due to a postoperative hematoma or to metabolic abnormality. The most common association in this series was with inadequate anticonvulsant prophylaxis. An approach to postoperative seizure prophylaxis and management is presented.

Brain↗

Computerized tomography in the diagnosis of retroperitoneal fibrosis.

We evaluated 4 patients with surgically proved retroperitoneal fibrosis by computerized tomography and ultrasound. Retroperitoneal fibrosis was diagnosed correctly in all 4 patients by computerized tomography but was detected by ultrasound in only 1. On computerized tomography, retroperitoneal fibrosis demonstrated a characteristic soft tissue mass enveloping the abdominal aorta, inferior vena cava and ureters. Computerized tomography was capable of detecting the abnormality with greater reliability than ultrasound, and was far superior in delineating the extent of the process and its relation to adjacent abdominal structures. Computerized tomography is the method of choice in the preoperative evaluation evaluation of retroperitoneal fibrosis. It also is anticipated that computerized tomography will prove equally useful in the postoperative followup of this disease.

Adolescent↗

Posttraumatic meningitis in adolescents and children.

To define the clinical features of posttraumatic meningitis in the pediatric age group, we have reviewed 7 cases presenting to Children's Hospital-San Diego between 1981 and February 1988. Ages ranged from 3 to 16 years with 4 of the 7 patients being adolescents (greater than 13 years of age). These 4 adolescents accounted for 25% of the adolescent bacterial meningitis and all cases of nonmeningococcal meningitis in this age group. Six of 7 patients had positive cerebrospinal fluid (CSF) cultures and positive blood cultures. Organisms were Streptococcus pneumoniae (4), group A streptococcus (1), and Haemophilus influenzae (1). Five of the 7 patients required intensive cardiovascular and respiratory support. Four patients had a good neurologic recovery, 2 patients had neurologic sequelae, and 1 suffered sensorineural hearing loss. These data suggest that direct invasion of the CSF by bacteria may cause sepsis and cardiovascular compromise. Further, in adolescents with nonmeningococcal bacterial meningitis, a history of previous head trauma and CSF leakage should be sought and radiographic evaluation for CSF fistula should be considered.

Adolescent↗