Biomedical subjects

R L Davis

Publications and source records attributed to R L Davis.

At least 271 records · Page 15Linked to original sources

PubMed1987

Pharmacokinetics of ciprofloxacin in cystic fibrosis.

We studied the pharmacokinetics of ciprofloxacin in 12 adult males with and 12 adult males without cystic fibrosis (CF). In a randomized crossover sequence, the subjects received 200 mg intravenously or 750 mg orally. With intravenous dosing, subjects also received 651 mg of iothalamate, a marker of glomerular filtration, and 700 mg of antipyrine, an indicator of hepatic oxidative drug metabolism. Pharmacokinetic parameters were determined by model independent methods. In the CF subjects, the ciprofloxacin concentration in serum during the first hour after intravenous administration was higher, and the oral absorption rate was slower. Other parameters did not differ between the groups. Mean concentrations in serum 5 min postinfusion were 3.08 and 2.14 micrograms/ml, and mean peak concentrations after oral dosing were 3.24 and 3.34 micrograms/ml in subjects with and without CF, respectively. Mean values for elimination half-life in all subjects were 4.8 and 5.0 h after intravenous and oral administration, respectively. The mean renal clearances in all subjects after intravenous and oral administration were 19.4 and 14.5 liters/h and accounted for 64 and 47% of the total clearance, respectively. These values were significantly greater than renal iothalamate clearance, indicating that tubular secretion contributed to the renal clearance of ciprofloxacin. A total of 69 and 35.4% of the administered ciprofloxacin was recovered from the urine within 48 h after intravenous and oral administration, respectively. The mean bioavailability was 71.2% and did not differ between the groups. We conclude that similar dosing regimens can be used to treat patients with CF and their normal counterparts.

Administration, Oral↗

PubMed1987

Efficacy of irradiation for incompletely excised acoustic neurilemomas.

The records of 124 patients treated for acoustic neurilemoma at the University of California, San Francisco, from 1945 through 1983 were reviewed. Patients were classified by the extent of surgical resection: total, nearly total (90% to 99% resection), subtotal (less than 90% resection), or biopsy. Thirty-one patients received irradiation as part of their primary treatment. Total resection of tumor, without irradiation, was associated with a 3% chance of local recurrence. One of 15 patients who had nearly total resection of their tumor and did not receive postoperative irradiation suffered a recurrence, compared with neither of the two patients who received postoperative irradiation (greater than 45 Gy) following nearly total resection. Postoperative irradiation (greater than 45 Gy) decreased the recurrence rate after subtotal resection from 46% (six of 13 cases without irradiation) to 6% (one of 17 cases: p = 0.01). All three patients treated by biopsy alone received postoperative irradiation (greater than 45 Gy), and none had a recurrence. Six patients were treated with preoperative irradiation because of excessive tumor vascularity; four are without evidence of disease 12 to 23 years later. Only three of seven patients treated with irradiation for tumor recurrence after surgical resection survived. It is concluded that postoperative irradiation significantly decreased the chance for local tumor progression following subtotal resection of acoustic neurilemoma, and that postoperative irradiation may be effective therapy following treatment by biopsy. Patients with total or nearly total resection appeared not to benefit from postoperative irradiation.

Adolescent↗

PubMed1987

Recurrent malignant gliomas: survival following interstitial brachytherapy with high-activity iodine-125 sources.

The authors report survival data for the first 41 patients treated for recurrent malignant gliomas with interstitial brachytherapy at the University of California, San Francisco (1980-1984). Iodine-125 (125I) sources were temporarily implanted using stereotaxic techniques. The median survival period for 18 patients with recurrent glioblastomas was 52 weeks after brachytherapy; two patients are alive more than 5 years after brachytherapy. The median survival period for 23 patients with recurrent anaplastic astrocytomas is 153 weeks after brachytherapy, with 10 patients alive more than 3 years and four patients alive more than 4 years after brachytherapy. Both groups did significantly better (p less than 0.01) than groups of patients with the same diagnoses and similar general characteristics who were treated at recurrence with chemotherapy alone. Because of deterioration of their clinical condition and evidence of recurrence from computerized tomographic scans, 17 (41%) of 41 patients required reoperation 20 to 72 weeks after brachytherapy. Despite the invariable presence of apparently viable tumor cells mixed with necrotic tissue in the resected specimen, nine patients have survived more than 2 years after reoperation and two of the nine are still alive 4 years after reoperation. The authors conclude that brachytherapy with temporarily implanted 125I sources for well-circumscribed, hemispheric, recurrent malignant gliomas is effective and offers a chance for long-term survival even though focal radiation necrosis can seriously degrade the quality of survival in a minority of patients.

Adolescent↗

PubMed1987

Phase I-II study of eflornithine and mitoguazone combined in the treatment of recurrent primary brain tumors.

Eflornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, and mitoguazone (MGBG), a competitive inhibitor of S-adenosylmethionine decarboxylase, were evaluated in a phase I-II study for patients with primary recurrent malignant brain tumors. All patients had failed prior radiation therapy and most had also failed prior chemotherapy. Two dose schedules were used, with the second schedule (Group II) a modification of the first schedule (Group I). The Group II schedule, with different dose levels, was better tolerated than the Group I schedule. Gastrointestinal and myelotoxicity were dose-limiting in most patients, and tinnitus was dose-limiting in two patients. Nineteen of 33 evaluable patients had anaplastic gliomas, in whom response was observed in 21%, stable disease in 53%, and immediate progression after one course of therapy in 26%. Of six patients with glioblastoma multiforme, two had brief stabilization of disease. An additional patient with brainstem glioma and ependymoma also had disease stabilization. Four patients with medulloblastoma, a spinal cord mixed glioma, and one with oligodendroglioma failed DFMO-MGBG. Based on this study, we believe that a combination of DFMO and MGBG is well-tolerated and deserves further evaluation for patients with anaplastic gliomas, particularly those that appear to be biologically slow growing.

Adolescent↗

PubMed1987

Pathology of delayed radiation brain damage: an experimental canine model.

Delayed radiation damage of normal brain can be a devastating complication of radiation therapy and generally occurs months to years after the initiation of therapy. Primarily restricted to the white matter, radiation damage is characterized by a number of histopathologic changes including coagulation necrosis, vascular alterations with fibrinoid necrosis, edema, and demyelination. Normal dogs were exposed to either 10, 15, or 30 Gy of X rays to a single hemisphere and the gross and histopathologic changes were evaluated qualitatively. A spectrum of changes was observed ranging from white matter edema to extensive white matter necrosis, and the extent, location, and type of damage were dependent upon radiation dose. Histopathologic changes were separated into three major categories based on the character and size of the lesions, with the most severe changes being similar to the types of changes described in human patients who have developed delayed radiation necrosis. Less severe forms of damage such as multifocal, sometimes confluent areas of microscopic necrosis with spongiotic borders and edema with severe axonal swelling were also observed. These latter changes are not well recognized as being due to radiation. The findings of this study also indicate that many of the changes ascribed to combined treatment with methotrexate and radiation in humans are induced in the normal dog brain by radiation alone. The results of his study show that the dog is a suitable model of the human brain for studying radiation brain injury and may be useful for investigation of drug-radiation interactions.

Animals↗

PubMed1987

Subjective comparison of office perimetry.

The Fieldmaster 50 and the Dicon AP2000 are automated perimeters which perform threshold static testing. In this study, 50 patients and 10 perimetrists determined their preference after being randomly tested by each automated perimeter. Subjects responded to a series of questions comparing the perimeters. The Fieldmaster 50 automated perimeter was preferred for most of the question categories.

Evaluation Studies as Topic↗

PubMed1986

Proliferative potential of human meningiomas of the brain. A cell kinetics study with bromodeoxyuridine.

Twenty patients with intracranial meningiomas were given a 1-hour intravenous infusion of bromodeoxyuridine (BrdU), 200 mg/m2, at the time of surgery to label tumor cells in the DNA synthesis phase (S phase). The excised tumor specimens were fixed with 70% ethanol, embedded in paraffin, sectioned, and stained by an indirect immunoperoxidase method using anti-BrdU monoclonal antibody as the first antibody. The BrdU labeling index (LI), or S-phase fraction, was determined by counting the number of BrdU-labeled cells in the tissue sections. The average LIs for nonmalignant (11 cases) and histologically malignant meningiomas (seven cases) were 0.45% and 3.9% respectively (P less than 0.05). Two hemangiopericytic variants showed average LIs of 0.53% and 4.1%. Four of seven malignant meningiomas and both hemangiopericytomas were recurrent tumors. Nine of 20 meningiomas had an LI greater than 1%, and six of those nine (67%) were recurrent. Thus, meningiomas with an LI greater than 1% appear to grow faster and recur more frequently than those with LIs less than 1%; the higher LI may indicate biological malignancy. The measurement of BrdU LI in meningioma may prove valuable in establishing the diagnosis of "malignant meningioma."

Adult↗

PubMed1986

Reaction sequences for (Na+ + K+)-dependent ATPase hydrolytic activities: new quantitative kinetic models.

To delineate better the reaction sequence of the (Na+ + K+)-ATPase and illuminate properties of the active site, kinetic data were fitted to specific quantitative models. For the (Na+ + K+)-ATPase reaction, double-reciprocal plots of velocity against ATP (in the millimolar range), with a series of fixed KCl concentrations, are nearly parallel, in accord with the ping pong kinetics of ATP binding at the low-affinity sites only after Pi release. However, contrary to requirements of usual formulations, Pi is not a competitor toward ATP. A new steady-state kinetic model accommodates these data quantitatively, requiring that under usual assay conditions most of the enzyme activity follows a sequence in which ATP adds after Pi release, but also requiring a minor alternative pathway with ATP adding after K+ binds but before Pi release. The fit to the data also reveals that Pi binds nearly as rapidly to E2 X K X ATP as to E2 X K, whereas ATP binds quite slowly to E2 X P X K: the site resembles a cul-de-sac with distal ATP and proximal Pi sites. For the K+-nitrophenyl phosphatase reaction also catalyzed by this enzyme, the apparent affinities for both substrate and Pi (as inhibitor) decrease with higher KCl concentrations, and both Pi and TNP-ATP appear to be competitive inhibitors toward substrate with 10 mM KCl but noncompetitive inhibitors with 1 mM KCl. These data are accommodated quantitatively by a steady-state model allowing cyclic hydrolytic activity without obligatory release of K+, and with exclusive binding of substrate vs. either Pi or TNP-ATP. The greater sensitivity of the phosphatase reaction to both Pi and arsenate is attributable to the weaker binding by the occluded-K+ enzyme form occurring in the (Na+ + K+)-ATPase reaction sequence. The steady-state models are consistent with cyclical interconversion of high- and low-affinity substrate sites accompanying E1/E2 transitions, with distortion to low-affinity sites altering not only affinity and route of access but also separating the adenine- and phosphate-binding regions, the latter serving in the E2 conformation as the active site for the phosphatase reaction.

Animals↗

PubMed1986

Primary central nervous system lymphoma in acquired immune deficiency syndrome: a clinical and pathological study.

Twenty cases of primary lymphoma of the central nervous system associated with acquired immune deficiency syndrome were seen over a period of four years and were studied clinically and pathologically. Biopsy established the diagnosis in 11 cases, and autopsy confirmed it in 9. Multicentricity was demonstrated in all cases for which there was adequate autopsy material. Both large-cell immunoblastic and small noncleaved lymphomas were seen, and marker studies in 5 patients established that the lymphomas were of B-cell origin. Neurological symptoms and signs, cerebrospinal fluid characteristics, and radiographic appearance were reviewed. The clinical and radiographic picture is nonspecific and histological confirmation is essential for diagnosis. Although the tumor appears to be radiosensitive, prognosis is extremely poor, with an average survival of less than two months.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Fluoride and beryllium interact with the (Na + K)-dependent ATPase as analogs of phosphate.

Fluoride irreversibly inhibits the (Na + K)-ATPase, and this inactivation requires divalent cations (Mg2+, Mn2+, or Ca2+), is augmented by K+, but is diminished by Na+ and by ATP. Prior incubation with the aluminum chelator deferoxamine markedly slows inactivation, whereas adding 1 microM AlCl3 speeds it, consistent with AlF-4 being the active species. Prior incubation of the enzyme with vanadate also blocks inactivation by fluoride added subsequently. Fluoride stimulates ouabain binding to the enzyme, and thus the analogy between AlF-4 and both orthophosphate and orthovanadate is reflected not only in the similar dependence on specific ligands for their enzyme interactions and their apparent competition for the same sites, but also in their common ability to promote ouabain binding. Beryllium also irreversibly inhibits the enzyme, and this inactivation again requires divalent cations, is augmented by K+, but is diminished by Na+ and by ATP. Similarly, prior incubation of the enzyme with vanadate blocks inactivation by beryllium added subsequently. Inactivation by beryllium, however, does not require a halide, and, unlike inactivation by fluoride, increases at basic pHs. These observations suggest that beryllium, as beryllium hydroxide complexes, acts as a phosphate analog, similar to AlF-4 and vanadate.

Aluminum↗

PubMed1986

Intracranial ependymomas: results of treatment with partial or whole brain irradiation without spinal irradiation.

Twenty patients with intracranial ependymoma (16) or anaplastic ependymoma (4) received post-operative radiation therapy at the University of California, San Francisco from 1959 through 1981. No patient received prophylactic spinal irradiation. The actuarial survival at 5, 10, and 15 years for 15 patients with ependymoma who received greater than 45 Gy was 67, 57, and 46%, respectively. Only one patient (7%) developed clinically recognized spinal metastases; this patient was eventually shown to have tumor at the primary site, within the irradiated volume. Six of 11 patients treated with partial brain irradiation had an intracranial recurrence, versus 1 of 4 patients treated with whole brain irradiation. Three patients were autopsied after failing partial brain irradiation for an ependymoma and the site of failure was within the irradiated volume of each patient. Partial brain irradiation was used to treat 4 patients with anaplastic ependymoma. One developed a local recurrence within the irradiated volume. The other three survived longer than 10 years. At UCSF, most patients with low grade ependymomas are presently treated with partial brain irradiation, but whole brain plus spinal irradiation is used for anaplastic tumors.

Adolescent↗

PubMed1986

Molecular analysis of cDNA clones and the corresponding genomic coding sequences of the Drosophila dunce+ gene, the structural gene for cAMP phosphodiesterase.

We have isolated and sequenced cDNA clones representing portions of the polyadenylylated transcripts of the dunce+ gene. These define an open reading frame of 1086 bases and some of the 5'- and 3'-untranslated regions of the transcripts. The deduced amino acid sequence is strikingly homologous to the amino acid sequence of a Ca2+/calmodulin-dependent cyclic nucleotide phosphodiesterase isolated from bovine brain and more weakly related to the predicted amino acid sequence of a yeast cAMP phosphodiesterase. These homologies, together with prior genetic and biochemical studies, provide unambiguous evidence that dunce+ codes for a phosphodiesterase. In addition, the dunce+ gene product shares a seven-amino acid sequence with a regulatory subunit of cAMP-dependent protein kinase that is predicted to be part of the cAMP binding site. We also identify a weak homology between a region of the dunce+ gene product and the egg-laying hormone precursor of Aplysia californica. The open reading frame is divided in the genome by four introns.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1986

The memory gene dunce+ encodes a remarkable set of RNAs with internal heterogeneity.

We have previously isolated the region of the Drosophila melanogaster X chromosome which contains the dunce+ gene and mapped the dunce2 mutation by recombination to a 10- to 12-kilobase (kb) interval (R. L. Davis and N. Davidson, Mol. Cell. Biol. 4:358-367, 1984). Here, we examine the expression of the dunce+ chromosomal region and identify the dunce+ gene within that region. A region of ca. 25 kb which contains the 10- to 12-kb interval to which dunce2 was mapped codes for polyadenylated RNAs of 9.6, 7.4, 7.2, 7.0, 5.4, and 4.5 kb in adult flies. These transcripts are encoded by the same DNA strand and share sequences of some exons, indicating that the transcripts arise from the same gene. Some genome probes internal to the ca. 25-kb coding region show transcript-specific hybridization, demonstrating alternate usage of exonic sequence information in the formation of the mature transcripts. The basis for this internal heterogeneity in RNAs is most likely alternative splicing. Two dunce mutants examined show aberrant RNA expression from this coding region, confirming that this region is the dunce gene. The developmental expression of these transcripts has been examined. The 5.4-kb RNA is present at all developmental stages. The 9.6-, 7.4-, 7.2-, and 7.0-kb RNAs are not expressed at detectable levels in embryos, but are detected in late embryogenesis and in later developmental stages. The 4.5-kb species is found in early embryos and adults, but not in intermediate stages. We discuss the remarkable transcript heterogeneity and expression pattern with respect to the important function this gene performs in neurobiological and other physiological processes.

Animals↗

PubMed1986

Normal brain iodine-125 radiation damage: effect of dose and irradiated volume in a canine model.

High-activity iodine-125 sources in plastic catheters were surgically placed in the cerebral white matter of healthy beagle dogs and later removed. Reference doses, calculated at a point 0.75 mm from the source, ranged from 10 to 40 Gy. Necrosis, vascular-related damage, and edema were quantified by computed tomography. Volumetric analyses were used to derive the relationship of dose and dose rate to necrosis and contrast enhancement. The extent of necrosis was related to irradiated volume; a minimum effective dose averaging 180-200 Gy was required to induce this type of damage. Contrast enhancement was less dependent on irradiated volume or total dose. The extent of radiation-induced edema was directly related to the volumes of necrosis plus contrast enhancement. Noninvasive serial studies in a well-characterized in vivo model can address specific clinically related questions on damage to normal tissue after interstitial irradiation.

Animals↗

PubMed1986

Pediatric central nervous system tumors: a cell kinetic study with bromodeoxyuridine.

Bromodeoxyuridine (BrdU), 150 to 200 mg/m2, was administered at the time of operation to 20 pediatric patients with neuroectodermal tumors to label tumor cells in the S phase. Immunocytochemical techniques were used on excised tumor specimens to detect cells containing BrdU, and the BrdU labeling index (LI) was calculated as the number of BrdU-labeled cells divided by the total number of cells counted. Four medulloblastomas, three glioblastomas multiforme, and two highly anaplastic astrocytomas had average BrdU LIs of 13.0 +/- 3.0% (SE), 12.7 +/- 4.3%, and 14.6 +/- 6.7%, respectively. Three of nine moderately anaplastic astrocytomas had BrdU LIs of greater than 1% (average, 6.5 +/- 2.4%), whereas six had LIs of less than 1%. In two juvenile pilocytic astrocytomas, which are considered slow-growing, the BrdU LIs were unexpectedly high, averaging 6.5 +/- 1.4%. Thus pediatric medulloblastomas, glioblastomas multiforme, highly anaplastic astrocytomas, and a minority of moderately anaplastic astrocytomas had high proliferative potentials, whereas most of the moderately anaplastic astrocytomas had low proliferative potentials. Although the number of cases in this study is still too small to yield statistically significant comparisons, the results indicate that some pediatric tumors have considerably higher LIs than histologically similar adult tumors studied previously.

Adolescent↗

PubMed1986

Influence of oxygen on the heartbeat rhythm of the leech.

Raising and lowering the oxygen content in the fluid bathing the skin of the leech modified the frequency of the heartbeat. In raised concentrations of oxygen, the period between bursts of impulses in the heart excitor motoneurones (HE cells) was reduced. Conversely, with lowered oxygen concentrations bathing the skin, the heart rate was slowed, with longer periods between bursts of firing in the HE motoneurones. Changes in oxygen concentration did not affect HE motoneurone firing patterns in preparations in which the CNS was dissected from the skin and surrounding body tissues. Various other stimuli were tried, including stroking, pinching, stretching the skin, blood vessels and gut, as well as changing the temperature. None of these stimuli mimicked the specific effects of oxygen on rhythmicity. It is concluded that peripheral receptors sensitive to changes in oxygen tension are able to influence the central neuronal circuits responsible for generating the rhythm of the heartbeat.

Animals↗

PubMed1986

Foci of MRI signal (pseudo lesions) anterior to the frontal horns: histologic correlations of a normal finding.

Review of all normal magnetic resonance (MR) scans performed over a 12-month period consistently revealed punctate areas of high signal intensity on T2-weighted images in the white matter just anterior and lateral to both frontal horns. Normal anatomic specimens were examined with attention to specific characteristics of this region. Three unique features typify the brain tissues that correspond to the foci of high signal. First, this region of the brain is notable for its loose network of axons with low myelin content. Second, pathologic scrutiny revealed an entity called "ependymitis granularis," which represents patchy loss of the ependyma in the frontal horns with astrocytic gliosis. Third, flow of interstitial fluid within this region of the brain tends to converge at the dorsal-lateral angle of the frontal horns. All these factors contribute to increased water content locally, which results in foci of high signal intensity anterior to the frontal horns in all normal MR scans.

Adolescent↗

PubMed1986

In situ cell kinetics studies on human neuroectodermal tumors with bromodeoxyuridine labeling.

Thirty-eight patients undergoing surgical removal of neuroectodermal tumors of the central nervous system were given a 1-hour intravenous infusion of bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, to label tumor cells in the deoxyribonucleic acid (DNA) synthesis phase (S-phase). The excised tumor specimens were divided into two portions: one was fixed with 70% ethanol and embedded in paraffin and the other was digested with an enzyme cocktail to make a single-cell suspension. The paraffin-embedded tissues were stained by an indirect peroxidase method using anti-BUdR monoclonal antibody (MA) as the first antibody. Single-cell suspensions were reacted with fluorescein isothiocyanate (FITC)-conjugated anti-BUdR MA's for flow cytometric analysis. S-phase cells that had incorporated BUdR into their DNA were well stained by both methods. The percentage of BUdR-labeled cells, or S-phase fraction, was calculated in tissue sections by microscopic examination and in single-cell suspensions by flow cytometric analysis. The biological malignancy of the tumors was reflected in the S-phase fractions, which were 5% to 20% for glioblastoma multiforme, medulloblastoma, and highly anaplastic astrocytoma, but less than 1% in most moderately anaplastic astrocytomas, ependymomas, and mixed gliomas. Two juvenile pilocytic astrocytomas and two low-grade astrocytomas from children had high S-phase fraction despite the fairly benign and slow-growing nature of these tumors. These results indicate that the S-phase fraction obtained immunocytochemically with anti-BUdR MA's may provide useful information in estimating the biological malignancy of human central nervous system tumors in situ.

Adolescent↗