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Biomedical subjects

P C Davis

Publications and source records attributed to P C Davis.

At least 55 records · Page 3Linked to original sources

The CERAD experience, Part VIII: Neuroimaging-neuropathology correlates of temporal lobe changes in Alzheimer's disease.

We compared premortem neuroimaging findings with neuropathologic evidence of temporal lobe atrophy in 20 patients with Alzheimer's disease (AD) confirmed by autopsy. There were significant correlations between temporal horn enlargement observed by neuroimaging and hippocampal atrophy at autopsy, and between the overall cerebral atrophy severity on neuroimaging and scores on the Mini-Mental State Examination. This report confirms previous studies correlating temporal lobe atrophy on neuroimaging with a clinical diagnosis of AD, although more precise neuroimaging techniques are needed for use in multicenter studies of AD.

Alzheimer Disease↗

Clinical, neurodiagnostic, and MR findings in children with spinal and brain stem multiple sclerosis.

PURPOSE: To describe the clinical, neurodiagnostic, and MR findings in seven children with brain stem and spinal multiple sclerosis. METHODS: Spinal or brain stem multiple sclerosis was diagnosed in seven children between 1986 and 1992. All patients had neurologic and MR examinations as well as neurodiagnostic testing, including spinal fluid analysis and brain stem and auditory evoked potentials. RESULTS: Three children had clinical findings and masslike lesions in the brain stem (two) or spinal cord (one) suggestive of neoplasm, which prompted biopsy (two) or radiation therapy (one). Five of six patients with spinal involvement had cord swelling with increased signal on T2-weighted images over at least three cord segments, and two children had essentially holocord involvement. Three children had normal cranial MR at presentation. CONCLUSIONS: Multiple sclerosis involvement of the brain stem and spinal cord may be associated with extensive swelling and MR signal changes suggestive of neoplasm without typical cerebral white matter abnormalities. Serial clinical and neuroimaging examinations may be necessary to make a definitive diagnosis of multiple sclerosis in children.

Adolescent↗

The brain in older persons with and without dementia: findings on MR, PET, and SPECT images.

Neuroimaging plays an increasingly important role in the evaluation of dementias of older adults. Although no unequivocal diagnostic test other than biopsy is currently available for Alzheimer's disease and some other dementias during life, neuroimaging techniques are an integral part of the examination and follow-up of patients with dementia. This review describes findings in the brains of patients with normal aging and in elderly patients with dementia, as shown by MR imaging and MR spectroscopy, positron emission tomography (PET), and single-photon emission computed tomography (SPECT) and correlated with clinical and pathologic features.

Aged↗

Delayed intracranial hemorrhage in children after suboccipital craniectomy.

OBJECTIVE: The purpose of this study was to report the clinical and imaging findings of seven children who developed extraaxial, intracranial hemorrhage 3-12 years after suboccipital craniectomy for neoplasia. We attempt to explain the hemorrhages based on a previously reported hypothesis of neomembrane formation associated with dural substitutes used to repair large dural defects. MATERIALS AND METHODS: Clinical charts (seven patients), surgical and pathologic findings (four patients), and imaging studies (CT scans and MR images in four; CT scans, MR images, and angiograms in one; and CT scans only in two patients) were reviewed retrospectively. Hemorrhage occurred 3-12 years after suboccipital craniectomy for tumor (ependymoma in two, medulloblastoma in three, astrocytoma in one, and ganglioglioma in one). Silastic dural substitute was used to repair the surgical wound in six cases and human dural graft in one case. Hematomas were spontaneous in four and occurred after minor head trauma in three. Four patients had multiple hemorrhagic episodes. RESULTS: CT scans and MR images showed acute extraaxial hemorrhages at the craniectomy site without contiguous residual or recurrent neoplasia in all patients. No intraaxial or intratumoral hemorrhage was detected. Findings on cerebral angiograms in one patient were normal. Four patients underwent surgical exploration of the hematoma and craniectomy site; no macroscopic source of bleeding was detected. The hematomas were not associated with recurrent tumor pathologically. CONCLUSION: Delayed, benign extraaxial hematomas may occur in children who have undergone craniectomy for tumors of the posterior fossa and have had dural substitute used to repair large defects. Fragile vessels associated with nonmembranes have been proposed as the source of hemorrhage.

Brain Neoplasms↗

Anatomic and physiologic imaging of Alzheimer's disease.

At present, no imaging modality is considered the standard diagnostic test for AD. On anatomic studies, severity of temporal lobe and hippocampal atrophy are the most reliable findings in AD, although overlap of these findings among AD, aging, and other dementias mitigate the value of these measures for application to the individual case. Although somewhat cumbersome for routine use, quantitative MR measurements offer more precise comparison of degrees of atrophy. Functional imaging may demonstrate abnormalities of perfusion or metabolism that precede anatomic changes (PET, SPECT, or MRS), yet these techniques generally require additional anatomic information from MR for interpretation. Newer investigational MR techniques such as MRS and functional MR in combination with conventional MR imaging have the potential to combine metabolic with anatomic imaging in one examination. A combination of both metabolic and anatomic imaging studies may ultimately offer better sensitivity and specificity for diagnosis, monitoring, and follow-up of AD.

Alzheimer Disease↗

A specific radioimmunoassay for the measurement of ICI 200,880, an elastase inhibitor, in human serum.

ICI 200,880, 4-(4-chlorophenylsulphonylcarbamoyl)benzoyl-L-valyl-L-proline-1(RS )-(1-trifluoroacetyl-2-methylpropyl)amide (I), is a human neutrophil elastase inhibitor in development by ICI Pharmaceuticals Group. A specific and sensitive radioimmunoassay has been developed for this compound in human serum. An hydroxysuccinimide ester analogue of ICI 200,880 was coupled to the lysine residues of bovine serum albumin, characterized by gel electrophoresis and injected into rabbits to stimulate antibody formation; a highly specific, high titre antibody was obtained. An 125I-diiodinated 4-hydroxy-phenyl derivative of ICI 200,880 was utilized as the radiolabelled antigen. Satisfactory zero and non-specific binding were achieved with a 2-h pre-incubation of ICI 200,880 and antiserum at 37 degrees C, followed by the addition of radiolabelled antigen and a second 2-h incubation. Separation of bound and free radiolabel was achieved by employing PEG-goat anti-rabbit IgG separant. Sensitivity of 25 pg ml-1 ICI 200,880 in human serum was achieved (n = 12), with quantitative recovery of 106%, inter-assay precision of 6.3% and an average relative binding statistically different than that of pooled human serum. Serum quality control samples spiked at 600 and 100 pg ml-1 ICI 200,880 averaged 104% recovery over 6 validation days, with intra-assay precision of 12.8% RSD and inter-assay precision of 9.2% RSD (n = 24). Cross-reactivity of the ICI 200,880 antibody to three known metabolites and several analogues was negligible. Over 1200 clinical samples following aerosol administration of ICI 200,880 have been analysed by this procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

CLIX: a search algorithm for finding novel ligands capable of binding proteins of known three-dimensional structure.

A computer algorithm, CLIX, capable of searching a crystallographic data-base of small molecules for candidates which have both steric and chemical likelihood of binding a protein of known three-dimensional structure is presented. The algorithm is a significant advance over previous strategies which consider solely steric or chemical requirements for binding. The algorithm is shown to be capable of predicting the correct binding geometry of sialic acid to a mutant influenza-virus hemagglutinin and of proposing a number of potential new ligands to this protein.

Algorithms↗

An evaluation of abdominal staging procedures performed in pediatric patients with advanced Hodgkin's disease: a report from the Childrens Cancer Study Group.

Forty-nine children and adolescents underwent staging laparotomy in the course of a cooperative group (CCG) study of advanced Hodgkin's disease (HD). The purpose of the study was to evaluate the toxicity of a regimen of 12 cycles of doxorubicin, bleomycin, vinblastine, and imidazole carboxamide (ABVD) plus 2,100 cGy regional irradiation in patients with stage III-IV disease. Review of the biopsies and specimens from these 49 laparotomies identified distinct patterns of abdominal involvement and permitted an evaluation of the importance of different aspects of the staging procedure and an assessment of the value of non-invasive techniques in determining the extent of abdominal disease. The major observations from these studies were: (1) computed tomography (CT) and gallium 67 scans (GA) were specific (few false positives), but not sensitive, indicators of abdominal disease; (2) negative findings at laparotomy in 29 patients permitted a contraction of the abdominal radiation fields with no subsequent abdominal recurrence in these patients; (3) in five patients, stage IV status was established only by laparotomy and open hepatic biopsy; (4) all patients with lower abdominal or pelvic involvement also had upper abdominal node or splenic involvement; (5) involvement of splenic hilar nodes was a sensitive predictor of splenic involvement; (6) disease in the inferior paraaortic nodes accurately predicted the presence of more distal disease, ie, in the iliac or pelvic node groups; and (7) in a limited experience, transposition of the ovaries protected ovarian function from the effects of pelvic irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part III. Reliability of a standardized MRI evaluation of Alzheimer's disease.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed procedures for standardized imaging and reporting of magnetic resonance (MR) findings in Alzheimer's disease (AD) for use by neuroradiologists in multiple medical centers using a variety of MR equipment and field strengths. After initial pretesting, we revised the protocol, expanded the summary rating scale to seven points, and added more illustrations. Fourteen participating neuroradiologists evaluated 28 MR scans of elderly patients, giving us the basis for judging interrater agreement. We obtained acceptable intraclass correlations (greater than 0.79) for rating the size of the lateral and third ventricles and the temporal horn. Less satisfactory intraclass correlations occurred when rating other areas, including (1) global atrophy of the brain (0.70); (2) dilatation of the sulci of the temporal lobe (0.66); (3) frequency, location, and severity of white matter lesions (0.77); (4) sylvian fissure enlargement (0.70); and (5) cerebral sulcal dilatation (0.64). We also saw considerable variation in the reporting of cortical and lacunar infarcts. Despite careful design of the rating methodology and readings by experienced neuroradiologists, we did not find satisfactory interrater agreement for interpreting MR findings in elderly subjects. These findings may explain the difficulties encountered in applying similar subjective rating techniques that meet with success at one institution to multicenter studies. More objective and reproducible procedures are needed for interpretation of neuroimaging findings of AD in multicenter studies.

Alzheimer Disease↗

Efficacy of gadoteridol for contrast-enhanced magnetic resonance imaging in children.

RATIONALE AND OBJECTIVES: This study assesses the efficacy of gadoteridol for contrast-enhanced magnetic resonance imaging (MRI) in children. METHODS: Patients were examined by MRI before and after receiving 0.10 mmol/kg gadoteridol. Blinded and unblinded readers analyzed brain and spine MRI studies from a multicenter clinical trial involving 101 patients at 11 sites. Ninety-two cases (76 brain, 16 spine) were evaluated by unblinded investigators, and 91 cases (76 brain, 15 spine) were evaluated by three neuroradiologists unaffiliated with any investigational site and blinded to clinical information. RESULTS: Unblinded readers noted enhancement of brain pathology in 70% of cases versus 50% to 67% among blinded readers. Unblinded readers determined that additional diagnostic information was available after contrast in 82% of brain studies (average, 64% for blinded readers) and would have changed patient diagnoses in 48% of these studies (average, 46% for blinded readers). In spine cases, enhancement of pathology was noted in 38% (unblinded) and 33% to 40% (blinded). Additional diagnostic information was available after contrast in 63% of spine studies (unblinded), or an average of 58% (blinded), and patient diagnoses would have changed in 20% (unblinded), or an average of 59% (blinded). CONCLUSIONS: Gadoteridol is suitable for enhanced MRI detection, localization, and characterization of central nervous system pathology in children.

Adolescent↗

Pituitary adenoma: correlation of half-dose gadolinium-enhanced MR imaging with surgical findings in 26 patients.

Sellar magnetic resonance imaging studies obtained with half doses of gadopentetate dimeglumine (0.05 mmol/kg) were prospectively interpreted and retrospectively rated in 26 patients who subsequently underwent transsphenoidal sellar surgery for suspected pituitary adenoma. Studies included a sagittal scout view followed by a non-contrast-material-enhanced, an immediate postcontrast, and a delayed postcontrast T1-weighted image (obtained at 1.0 or 1.5 T). Ten of 11 confirmed microadenomas were identified prospectively; all were identifiable in retrospect. Macroadenomas (12 cases) were well demonstrated. The high signal intensity of the posterior pituitary and of intrasellar hemorrhage was obscured on postcontrast studies. Delayed images proved unnecessary. This prospective evaluation suggests that a half-dose study is comparable to retrospective studies in which full-dose techniques were used for detection of micro- and macroadenomas. Imaging times are reasonably short, and cost of contrast material is potentially reduced. Confirmation with larger studies is required, and careful endocrinologic and clinical follow-up of nonsurgical patients is necessary.

Adenoma↗

The three-dimensional structure of the seed storage protein phaseolin at 3 A resolution.

The polypeptides of the trimeric seed storage protein phaseolin comprise two structurally similar units each made up of a beta-barrel and an alpha-helical domain. The beta-barrel has the 'jelly-roll' folding topology of the viral coat proteins and the alpha-helical domain shows structural similarity to the helix-turn-helix motif found in certain DNA-binding proteins.

Amino Acid Sequence↗

Efficacy and toxicity of 12 courses of ABVD chemotherapy followed by low-dose regional radiation in advanced Hodgkin's disease in children: a report from the Children's Cancer Study Group.

Sixty-four patients aged 2 to 18 years with advanced-stage Hodgkin's disease (HD) were treated on a Children's Cancer Study Group (CCSG) pilot toxicity study (521-P). Therapy consisted of 12 courses of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine (ABVD), followed by low-dose (2,100 cGy in 12 fractions) regional irradiation (RT). All patients were monitored for toxicity with particular attention to the pulmonary system. Six patients (9%) developed grade 3 or 4 pulmonary toxicity. Three had grade 3 toxicity based solely on changes in carbon monoxide diffusing capacity (DLCO) and remained well for more than 3 years after diagnosis. There was one fatality among the three symptomatic cases. In five cases, toxicity occurred prior to RT. One occurred after seven courses of ABVD, one after nine courses, and three after 10 courses. In one of these five cases, ABVD was stopped. The patient was given nitrogen mustard (mechlorethamine), vincristine, prednisone, and procarbazine (MOPP). This patient subsequently developed recurrence of HD and died of overwhelming sepsis. The other four continued on study and completed their chemotherapy. Three patients had no further bleomycin, and one continued bleomycin at 50% of the assigned dose. They all received mantle RT following chemotherapy, one with a boost dose to the mediastinum to 3,800 cGy and one with added RT to both lungs (1,050 cGy). In the sixth case of pulmonary toxicity, symptoms were first noticed 2 weeks after mantle RT to 3,500 cGy. This patient died of progressive respiratory failure. The event-free survival (EFS) and overall survival is 87% at 3 years. These early results indicate that this therapy is effective in advanced HD in children but has a 9% incidence of acute pulmonary toxicity.

Adolescent↗

Intracranial ganglioglioma: MR, CT, and clinical findings in 18 patients.

Eighteen cases of pathologically proved intracranial gangliogliomas were reviewed to determine their MR, CT, and clinical characteristics. Seventeen patients were evaluated with contrast-enhanced CT and 14 were studied by MR imaging. Eight tumors were predominantly cystic; half of these demonstrated some contrast enhancement, and five contained calcifications. These cystic gangliogliomas were located, in order of decreasing frequency, in the cerebellum, temporal, frontal, and parietal lobes. Ten tumors were solid; eight of these showed contrast enhancement, and only one contained calcifications. Small cysts were present in one solid mass. Solid gangliogliomas occurred preferentially in the temporal lobes. On MR, the findings were nonspecific and reflected the CT findings. In one patient who received gadolinium-DTPA the lesion did not enhance. Clinically, all patients presented with nonfocal long-standing symptoms and all but three were alive an average of 18 months after the initial diagnosis. Pathologists are recognizing ganglioglioma with increasing frequency, and although its radiographic characteristics vary, it should be included in the differential diagnosis when the above-described findings are encountered.

Adolescent↗

Primary cerebral neuroblastoma: CT and MR findings in 12 cases.

A retrospective CT, MR, and clinical study was performed in 12 patients, five children and seven adults, with histologically proved primary CNS neuroblastoma. The CT and MR appearances of this neoplasia were more variable than generally recognized. Although seven tumors were predominantly intraparenchymal masses with calcification and cyst formation, five were intra- or juxtaventricular. CT was preferable to noncontrast MR both at initial diagnosis and follow-up for identification of calcification, recurrent tumor at surgical sites, and leptomeningeal disease. Noncontrast MR was useful primarily for localization of peri- and intraventricular lesions. We conclude that primary CNS neuroblastoma has a more variable radiographic appearance than is generally recognized, and that an intra- or periventricular epicenter is common.

Adult↗