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Biomedical subjects

R L Davis

Publications and source records attributed to R L Davis.

At least 343 records · Page 19Linked to original sources

Determining the probability of an important difference in bioavailability.

Bioavailability studies usually compare formulations of a drug under the premise of equal bioavailabilities. Analyses of such studies may be questioned when large differences exist, but are not statistically significant, or when small differences are found which do reach statistical significance. In either case, the question of clinical significance is not addressed and remains problematic regardless of the outcome. The important question is, "Given the results of the study, what is the probability that a clinically important difference exists?" To obviate dependence on statistical significance, we propose a methodology which permits computation of the probability that a clinically important difference in bioavailability exists between two products, regardless of the results of conventional tests of hypothesis. The methodology permits a strong statement which defines the likelihood of a meaningful difference, rather than the "nonstatement" of current approaches. The approach is illustrated by a study in which a 2% (nonsignificant) difference in bioavailability was observed. Using the proposed methodology the analysis concluded that the odds are about 5 to 1 against there being a 20% difference in bioavailability between the formulations.

Bayes Theorem↗

Increased tissue differentiation using color display of multiple-energy CT scans.

Just as the average value of the attenuation coefficient can be represented by the brightness of the pixel, the energy structure of the attenuation coefficient determines its hue. This can be measured by filtering the x-ray beam with W, Pb, and Sn at 100, 120, adn 140 kVp, respectively. The color differences seen in (a) CT images of phantom materials such as iodine and calcium, (b) brain specimens containing hemorrhage, meningioma, glioblastoma, or metastases, and (c) preliminary in vivo head and body scans represent variations in chemical composition across the tissue section. Measurements show that energy-selective filtration increases the separation between effective energies while reducing the dose for the same number of transmitted x rays.

Color↗

Attempts to demonstrate virus in amyotrophic lateral sclerosis.

Neurons were isolated from the brain and spinal cord of five patients with clinical and pathologic evidence of amyotrophic lateral sclerosis (ALS). The following studies were carried out to detect the presence of infectious virus. Homogenates of isolated neurons were passaged in several cell lines at different temperatures; isolated neurons were cultured; and supernatant fluids were passaged on the cell lines. Neurons were also cocultivated and fused with continuous cell lines and subsequently passaged; isolated neurons were examined by electronmicroscopy and immunofluorescent techniques, using sera from ALS patients. No evidence of virus was found by these methods.

Amyotrophic Lateral Sclerosis↗

Metastases to primary intracranial meningiomas and neurilemomas.

Five cases of carcinoma metastatic to intracranial meningioma or neurilemoma are presented and compared with 20 similar cases reported in the literature. The phenomenon was most often seen on autopsy (17 of 25 cases) and was found more commonly in females (3:2), with nearly 90% of donor cancers being found in breast or lung. The existence of the donor tumor, which was always found to be widely disseminated, was known prior to autopsy in only half the cases.

Adenocarcinoma↗

Selective immunodeficiency and malignant lymphoma of the central nervous system. Possible relationship to the Epstein-Barr virus.

This report presents the findings of a study of a 17-year-old male with a selective immunodeficiency to the Epstein-Barr virus, who died of a malignant lymphoma following clinical infectious mononucleosis. Autopsy findings and immunohistochemical techniques demonstrated a malignant lymphoma with B-lymphocyte characteristics which primarily involved the central nervous system (CNS). The relationship of the Epstein-Barr virus to lymphoproliferation is discussed.

Adolescent↗

Primary cerebral neuroblastoma: a light and electron microscopic study.

A small-cell neoplasm in the left temporal lobe of a 10 and a half year old boy was studied by light and electron microscopy. Routine sections of the mass showed a differentiating neuroblastoma with Homer Wright rosettes, several foci of immature neoplastic neurons (ganglion cells), and many mitoses, areas of necrosis and tumor vessels showing endothelial proliferation. Ultrastructurally, most cells resembled early fetal neuroblasts and also were similar to those in murine and peripheral human neuroblastomas.

Brain Neoplasms↗

Metastatic cystosarcoma phyllodes. A report of 2 cases presenting with neurological symptoms.

Two cases of cystosarcoma phyllodes of the breast are presented with central nervous system (CNS) metastases appearing several years after mastectomy for the primary lesion. Unusual features in these cases include the widespread metastases themselves, neurologic symptomatology and CNS involvement, metastases into a uterine leiomyoma and into an area of hepatic adenomatous hyperplasia, and glomus-like structures in one of the primaries with similar structures resembling glomus cells in metastases. The distant metastases were of stromal cells only and frequently surrounded epithelial cells to isolate the indigenous glandular structures. The concept that cytosarcoma is a peculiar stromal neoplasm rather than a tumor of dual neoplastic origin is discussed.

Breast Neoplasms↗

An immunohistological study of immunoglobulin content of primary central nervous system lymphomas.

Paraffin sections of surgical and autopsy material from 24 cases of primary CNS lymphoma were examined for the presence of cytoplasmic immunoglobulin by an immunoperoxidase technique. Definite staining for cytoplasmic immunoglobulin was observed in 13 cases, and in eight of these the pattern of staining was consistent with current concepts of monoclonality. In every case the histological diagnosis of malignant lymphoma was confirmed, and cases were subclassified by both the Lukes-Collins and the Rappaport classifications. Morphologically 12 of the 24 cases resembled immunoblastic sarcoma occurring outside the CNS. Other cases showed features of follicular center cell lymphoma or plasmacytoid lymphocytic lymphoma. Of those cases with positive immunoglobulin staining of tumor cells, the majority showed some plasmacytoid features. It was concluded that the primary CNS lymphomas resemble their counterparts occurring outside the CNS, and that at least a proportion are derived from the B lymphocyte.

Adolescent↗

Spinal subarachnoid metastasis from primary intracranial glioblastoma multiforme.

Twenty-five patients with glioblastoma multiforme were autopsied at our institution in 7 years. Spinal cords were examined in 20 and 5 were found to have spinal leptomeningeal metastases. Clinical and neuropathological findings of these 5 patients are presented and factors possibility influencing such spread are analyzed. Review of previous studies of intracranial glioblastomas discloses only 14 reported cases with spinal leptomeningeal metastases confirmed at autopsy since 1931. We conclude that spinal leptomeningeal metastases in glioblastoma multiforme are a common occurrence. These findings are of little significance at present with our poor success at control of the primary lesion. Frequency of involvement of the spinal subarachnoid space will be significant, when we are able to better treat the primary tumor. Knowledge of the significant possibility of this phenomenon will allow earlier and more frequent clinical diagnosis.

Adolescent↗

Effects of concomitant aspirin administration on the pharmacokinetics of indomethacin in man.

Ten healthy volunteers each received single and multiple 50-mg doses of indomethacin orally and a single 25-mg dose of [14C]indomethacin intravenously in the absence of and concomitantly with 1200 mg of aspirin as a single dose and in a chronic t.i.d. regimen. Systematic analysis of the data resulted in the isolation and quantification of aspirin's effects on the absorption, distribution, biotransformation, excretion, enterohepatic circulation, and accumulation of indomethacin. The effects of chronic aspirin were to suppress the renal clearance, to increase the biliary clearance, to decrease the efficiency of gastrointestinal absorption, and to enhance the enterohepatic circulation of indomethacin. On concomitant administration of 1200 mg of aspirin t.i.d., mean plasma levels of indomethacin were depressed by 20% after a single oral dose, by a smaller margin after multiple oral doses, and not at all after a single intravenous dose of indomethacin. The mean plasma concentration of orally administered indomethacin was decreased by 8% when given concurrently with a single 1200 mg dose of aspirin. Concomitant chronic therapeutic dosages of indomethacin had no effect on salicylate accumulation from repetitive doses of aspirin.

Adult↗

An unusual fibro-osseous component in intracranial lesions.

An unusual fibro-osseous component has been identified in intracranial lesions. Ultrastructurally this component appears to represent stages of membranous bone formation, but of an atypical and incomplete sort. The fibroosseous component may be an aberrant type of bony metaplasia and is seen in several lesions all of which probably do not share the same etiology although in each case meningeal or choroid plexus stroma appears to be involved.

Adult↗

Pathologic tumor type and response to treatment.

The general biology of the common primary brain tumors is reviewed, as are the results of surgery, radiation therapy, and chemotherapy for these neoplasms. The problems of classification, particularly of the astrocytomas, are noted, with the resultant difficulties in comparing different series. The development and consistent application of a widely acceptable nomenclature for brain tumors would be useful in the comparison of various therapies and for ease in communication. Further, a better general understanding of the biology of the various brain tumors is desirable. Reliable data relative to old or new forms of therapy seem to require national or regional studies in view of the relative rarity of some of these tumors. Except for medulloblastoma, the best results of therapy thus far are only slightly encouraging. We must also be aware that some of our treatments may do as much harm to some patients as their tumors; therefore, we must all strive for a high autopsy rate so that we can monitor our therapy and recognize unexpected complications as quickly as possible.

Adolescent↗

Disseminated toxoplasmosis with brain involvement in a renal allograft recipient.

A 47-year-old male with renal failure received a renal transplant which subsequently was rejected. After removal of the transplant the patient went into a catabolic state, and developed fever and hematochezia. The patient became septic, developed respiratory involvement. This is the eighth recorded case of central nervous system toxoplasmosis following renal transplantation.

Brain↗

Pretectal syndrome with metastatic malignant melanoma to the posterior commissure.

A 46-year-old man with a known metastatic tumor developed the sudden onset of upgaze paralysis, impaired convergence, eyelid retraction, pupillary light-near dissociation, convergence-retraction nystagmus, and ocular skew deviation in association with subarachnoid hemorrhage. Selective interruption of the posterior commissure by metastatic melanoma provided a precise anatomic correlation of the pretectal syndrome in man.

Autopsy↗