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Biomedical subjects

L A Young

Publications and source records attributed to L A Young.

At least 19 recordsLinked to original sources
PubMed2006

Discovery of two new satellites of Pluto.

Pluto's first known satellite, Charon, was discovered in 1978. It has a diameter (approximately 1,200 km) about half that of Pluto, which makes it larger, relative to its primary, than any other moon in the Solar System. Previous searches for other satellites around Pluto have been unsuccessful, but they were not sensitive to objects less, similar150 km in diameter and there are no fundamental reasons why Pluto should not have more satellites. Here we report the discovery of two additional moons around Pluto, provisionally designated S/2005 P 1 (hereafter P1) and S/2005 P 2 (hereafter P2), which makes Pluto the first Kuiper belt object known to have multiple satellites. These new satellites are much smaller than Charon, with estimates of P1's diameter ranging from 60 km to 165 km, depending on the surface reflectivity; P2 is about 20 per cent smaller than P1. Although definitive orbits cannot be derived, both new satellites appear to be moving in circular orbits in the same orbital plane as Charon, with orbital periods of approximately 38 days (P1) and approximately 25 days (P2).

Journal Article↗
PubMed2006

A giant impact origin for Pluto's small moons and satellite multiplicity in the Kuiper belt.

The two newly discovered satellites of Pluto (P1 and P2) have masses that are small compared to both Pluto and Charon-that is, between 5 x 10(-4) and 1 x 10(-5) of Pluto's mass, and between 5 x 10(-3) and 1 x 10(-4) of Charon's mass. This discovery, combined with the constraints on the absence of more distant satellites of Pluto, reveal that Pluto and its moons comprise an unusual, highly compact, quadruple system. These facts naturally raise the question of how this puzzling satellite system came to be. Here we show that P1 and P2's proximity to Pluto and Charon, the fact that P1 and P2 are on near-circular orbits in the same plane as Pluto's large satellite Charon, along with their apparent locations in or near high-order mean-motion resonances, all probably result from their being constructed from collisional ejecta that originated from the Pluto-Charon formation event. We also argue that dust-ice rings of variable optical depths form sporadically in the Pluto system, and that rich satellite systems may be found--perhaps frequently--around other large Kuiper belt objects.

Journal Article↗
PubMed1999

Validation of K-edge 125I brachytherapy enhancement with silver compounds.

Brachytherapy with radioactive seeds implanted within the tumour volume has demonstrated good success rates in treating certain cancers. In an effort to improve the curative rates in cancer patients, ongoing research is being conducted to enhance the amount of radiation dose that is absorbed within the tumour volume while minimizing the dose absorbed by the surrounding normal tissue. One method for enhancing tumour dose absorption with 125I brachytherapy seeds is to increase the number of photoelectric atomic interactions within the tumour volume by introducing small quantities of a silver compound, taking advantage of the K-edge effect. Because low-energy electrons and Auger electrons are the primary sources of brachytherapy dose enhancement, acquiring accurate experimental measurements of absorbed dose increases is a major challenge. To circumvent this problem, an x ray fluorescence excitation spectroscopy dosimetry technique supplemented with clinically accepted dosimetry calculations was developed to estimate relative absorbed dose increases in a water phantom containing up to 7.5 mM of silver. Excellent agreement was observed between theoretically derived Monte Carlo dosimetric predictions and experimental measurements. These results successfully demonstrated that K-edge enhanced 125I brachytherapy is indeed possible with future development of a non-toxic silver chelate.

Algorithms↗
PubMed1998

Nocturnal blood pressure in young patients with insulin-dependent diabetes mellitus: correlation with cardiac function.

Lack of a decline in nocturnal blood pressure is associated with an adverse effect on end organs in adults with insulin-dependent diabetes mellitus (IDDM). The role of the decline in nocturnal blood pressure in young patients with IDDM is not known. We studied 25 white subjects with IDDM (age = 20.8 +/- 3.7 years, mean +/- SD), 8 of whom were female. The duration of IDDM in these subjects was 12.9 +/- 5.4 years (mean +/- SD). We determined the values for glycosylated hemoglobin (HgbA1), 24-hour ambulatory blood pressure, diastolic cardiac function (the ratio of peak E wave to peak A wave velocity (E/A) and indexed peak filling rate ¿PFR/SV¿ by Doppler echocardiography), and albumin excretion rate. The HgbA1 level was 10.9% +/- 1.9% (mean +/- SD; normal range = 4.5%-8.5%). The HgbA1 concentration was inversely correlated (p < 0.005) with the decline in systolic (r = 0.57) and diastolic (r = -0.55) nocturnal blood pressure. Diastolic cardiac dysfunction ¿E/A ratio [r = 0.42, p < 0.03) and PFR/SV (r = 0.52, p < 0.01)¿ correlated with a smaller decrease in nocturnal diastolic blood pressure. An inverse correlation between decline in nocturnal systolic blood pressure and log albumin excretion rate (r = -0.37, p = 0.07) approached statistical significance. We conclude that poor glycemic control adversely affects nocturnal blood pressure and that the latter may play an important role in cardiac and possibly renal dysfunction in early IDDM.

Adolescent↗
PubMed1998

125I brachytherapy k-edge dose enhancement with AgTPPS4.

Photon activation is a radiotherapy technique in which an element is added to the absorbing medium to raise the probability that a photoelectric interaction will occur, thus causing an increase in the absorption of ionizing radiation. Binding energies of key elements within an absorbing medium are closely matched with the incident photon energies to maximize the production of free electrons and subsequent absorption of their kinetic energies. The purpose of this research was to quantify potential dose enhancement using a silver tetraphenyl sulfonato porphyrin (AgTPPS4) in tumors as a photon activator for use with interstitial 125I brachytherapy. A three-dimensional Monte Carlo dosimetry model was developed using the EGS4 coding system. The photon source was modeled using spectral gamma emissions from models 6702 or 6711 brachytherapy seeds for comparison. Absorbed dose within the tumor volume was calculated for AgTPPS4 concentrations ranging between 0 and 20 mmol/kg tumor weight. These theoretical studies demonstrated linear increases in dose absorbed by the tumor with corresponding increases in AgTPPS4 concentration. The required AgTPPS4 concentration (RSC) to achieve at least a ten percent absorbed dose increase is approximately 6.5 mmol/kg tumor weight for model 6702 seeds. In vivo biodistribution and in vitro toxicity studies were conducted to determine if the theoretically derived RSC could be achieved biologically. Cell toxicity studies showed that TPPS4 porphyrin derivatives were cytotoxic at concentrations required to provide significant brachytherapy dose enhancement. Reverse phase HPLC confirmed that toxicity was due to intrinsic properties of the TPPS4 molecule, not the presence of free silver, drug impurities, or metabolites. Further research is necessary to develop a nontoxic molecular carrier for delivering silver to the DNA of tumor cells.

Animals↗
PubMed1997

Disposition of enrofloxacin and its metabolite ciprofloxacin after intramuscular injection in juvenile Burmese pythons (Python molurus bivittatus).

Eleven juvenile Burmese pythons (Python molurus bivittatus) weighing 0.75-1.75 kg were randomly divided into two groups. Blood samples were obtained through surgically placed anterior carotid artery cannulas. Six pythons received a single i.m. injection of enrofloxacin at 5 mg/kg. Blood samples were obtained at 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hr postinjection. A mean (+/- SD) maximal plasma concentration of 1.66 (+/- 0.42) micrograms/ml was measured at 5.75 hr postinjection. The harmonic mean half-life was calculated to be 6.37 hr. The second group of five snakes received enrofloxacin at 5 mg/kg i.m. s.i.d. for 5 days. Blood was collected immediately before each injection and at 6 hr after each injection. Over the 5-day period, there was a stepwise increase in mean trough plasma concentrations of enrofloxacin. Clinically effective peak plasma enrofloxacin concentrations were attained after the first injection but did not significantly increase during the sampling period. Pharmacokinetic data were assessed against minimum inhibitory concentrations of enrofloxacin for Pseudomonas ssp. isolates in snakes obtained from historical data at the Veterinary Medical Teaching Hospital, University of Florida. Enrofloxacin should be administered at 10 mg/kg i.m. every 48 hr when treating Pseudomonas ssp. infections in juvenile Burmese pythons. Treatment of infections of more enrofloxacin-sensitive gram-negative bacteria could be achieved with the administration of an initial i.m. dose of 10 mg/kg followed by 5 mg/kg every 48 hr.

Animals↗
PubMed1996

Prospective, randomized, double-blind, placebo-controlled comparison of metoclopramide and ondansetron for prevention of posttonsillectomy or adenotonsillectomy emesis.

STUDY OBJECTIVE: To compare the antimetic efficacy of prophylactic ondansetron, metoclopramide, and placebo for prevention of postoperative vomiting in pediatric tonsillectomy or adenotonsillectomy patients. DESIGN: Prospective, randomized, double-blind, placebo controlled study. SETTING: Children's hospital. PATIENTS: 132 ASA status I and II children, ages 2 to 12 years, undergoing tonsillectomy or adenotonsillectomy. INTERVENTIONS: Patients received intravenous (IV) melodopramide 0.25 mg/kg, IV on dansetron 0.15 mg/kg, or IV saline placebo after induction of standardized halothane, nitrous oxide, and oxygen anesthesia. Muscle relaxants and their antagonists were allowed. Patients received postoperative analgesics as needed. MEASUREMENTS AND MAIN RESULTS: Incidence of postoperative vomiting, time of vomitting onset, and hospital length of stay (LOS) were measured. Patients who were admitted were excluded from LOS analysis. The postoperative incidence of vomiting was 54% for patients receiving metoclopramide, 26% for patients receiving ondansetron, and 69% for the placebo group. These differences were significant for ondansetron versus metoclopramide (p = 0.008) and placebo (p = 0.001). The mean (SD) LOS was significantly shorter for patients not vomiting 488 (88) minutes for vomiters versus 435 (65) minutes for non-vomiters. CONCLUSIONS: Prophylactic ondansetron is more effective than metoclopramide or placebo for the prevention of vomiting after tonsillectomy or adenotonsillectomy. Patients who do not vomit postoperatively have shorter LOS.

Adenoidectomy↗
PubMed1996

Genomic fingerprinting for epidemiological differentiation of Staphylococcus aureus clinical isolates.

We used genomic fingerprinting to investigate an outbreak of methicillin-resistant Staphylococcus aureus in the neonatal intensive care units (NICUs) of two hospitals. The hospitals are located in the same city and are part of the same medical care system. Fingerprinting was done by Southern blot hybridization with DNA probes for the genes encoding the S. aureus collagen adhesin (cna), fibronectin-binding proteins (fnbA and fnbB), and beta-toxin (hlb). Genomic DNA was digested with HaeIII (cna and fnbA-fnbB probes) or HindIII (hlb probe). Hybridization patterns could be distinguished on the basis of (i) the presence or absence of cna, (ii) the size of the restriction fragment containing the cna gene, (iii) restriction fragment length polymorphisms within fnbA and fnbB, (iv) the presence of a lysogenic phage within hlb, and (v) the sizes of the restriction fragments containing the phage-bacterial DNA junction fragments. Over a period of 4 months we examined a total of 46 isolates obtained from various wards within each hospital. Among these 46 isolates, we observed a total of 4 cna patterns, 11 fnbA-fnbB patterns, and 11 hlb patterns. Southern blots with HaeIII-digested genomic DNA and a combination of all three gene probes revealed a total of 16 clearly distinguishable patterns. A total of 22 of the 46 isolates were identical with respect to every genomic marker examined. A total of 21 of these 22 isolates were obtained from patients within an NICU. Nineteen of 21 isolates also exhibited identical antibiotic resistance profiles (antibiogram). Although 5 of the remaining 24 strains exhibited an antibiogram identical to those of the NICU isolates, all 24 strains could be distinguished from the NICU isolates by at least one genomic marker. These results suggest that the NICU isolates had a common origin and that genomic fingerprinting with the cna, fnbA, fnbB, and hlb gene probes can provide an important epidemiological tool for the identification of clinical isolates of S. aureus.

Base Sequence↗
PubMed1996

Placebo-controlled trial of gabapentin in patients with amyotrophic lateral sclerosis. WALS Study Group. Western Amyotrophic Lateral Sclerosis Study Group.

We designed a phase II trial to evaluate the efficacy of gabapentin in slowing the rate of decline in muscle strength of patients with amyotrophic lateral sclerosis (ALS) and to assess safety and tolerability. Gabapentin (800 mg) or placebo was administered t.i.d. in a randomized, double-blinded, placebo-controlled, trial for 6 months. We enrolled 152 patients at eight sites in the United States. The primary outcome measure was the slope of the arm megascore, the average maximum voluntary isometric strength from eight arm muscles standardized against a reference ALS population. A secondary outcome measure was forced vital capacity. Slopes of arm megascores for patients on gabapentin were compared with slopes of those taking placebo using a two-way ANOVA. We observed a nonstatistically significant trend (p = 0.057-0.08) toward slower decline of arm strength in patients taking gabapentin compared with those taking placebo (mean difference 24%, median 37%). We observed no treatment effect on forced vital capacity. Gabapentin was well tolerated by patients with ALS. These results suggest that further studies of gabapentin in ALS are warranted.

Acetates↗
PubMed1994

Interleukin-6 regulates expression of the syndecan-1 proteoglycan on B lymphoid cells.

Proteoglycans participate in hematopoiesis and immune responses by mediating cell adhesion and by binding and presenting growth factors to cells. However, the mechanisms that regulate proteoglycan expression on cells of the immune system have not been defined. Syndecan-1, a member of the syndecan family of integral membrane proteoglycans, is expressed by pre-B cells and plasma cells but is absent from circulating B cells. Because IL-6 is an important cytokine in both B cell differentiation and in the progression of B cell-related diseases, we examined the effect of IL-6 on syndecan-1 expression. Following growth of murine B lymphoid cells in medium containing IL-6, the level of syndecan-1 detected is dramatically reduced. This reduction in syndecan-1 expression is dependent on the concentration of IL-6 present in the medium, with syndecan-1 levels being 2.5- to 5-fold lower than those of controls when cells are grown in media containing 10 and 1000 U/ml of IL-6, respectively. The effect of IL-6 on syndecan-1 expression is time dependent, with syndecan-1 levels declining over the first 48 hr. This trend is reversible because following removal of exogenous IL-6, syndecan-1 levels increase within 24 hr to 80% of their control levels. The regulation of syndecan-1 expression by IL-6 appears to be via post-transcriptional mechanisms because syndecan-1 mRNA levels are not decreased following growth of cells in the presence of IL-6. Furthermore, IL-6 does not alter syndecan-1 structure and therefore its effect is different from that of TGF-beta which alters syndecan-1 glycosylation but not the number of syndecan-1 molecules at the cell surface. We conclude that IL-6 participates in the regulation of syndecan-1 expression on B lymphoid cells and, given its broad distribution, IL-6 may regulate proteoglycan expression on other cell types as well.

Animals↗
PubMed1993

A finite difference heat transfer analysis of a percutaneous transluminal microwave angioplasty system.

Finite difference time domain (FDTD) techniques have been developed to calculate the specific absorption rates (SAR) in hyperthermia models. The University of Utah Hyperthermia Research Group has extended these numerical techniques for developing a percutaneous transluminal microwave angioplasty applicator, calculating the SARs produced by a high energy electromagnetic field to remove atherosclerotic plaques in blood vessels. The objective of this research was to derive a method for calculating the bioheat transfer in biological tissue surrounding a microwave angioplasty applicator. A hypothetical model was developed and observations are discussed based on the numerical results of this study. A limited analysis on the thermal effects of microwave pulsing was also completed. Preliminary numerical calculations yielded reasonable results. Experimental laboratory tests are required to validate the accuracy of the numerical results found in this study. Further development of this thermal analysis method may greatly assist in future studies of new applicator configurations to ensure safe atherosclerotic plaque removal and to predict the resulting thermal environments.

Angioplasty, Balloon, Coronary↗
PubMed1992

Adhesion of B lymphoid (MPC-11) cells to type I collagen is mediated by integral membrane proteoglycan, syndecan.

Differentiating B lymphocytes undergo changes in cell-cell and cell-matrix adhesion that control their movement through a series of distinct microenvironments. The integral membrane proteoglycan, syndecan, is a candidate for mediating B lymphocyte-matrix interactions because it is expressed on B lymphocytes only at times when they associate with matrix, and because syndecan is known to behave as a matrix receptor on simple epithelia. However, syndecan from B lymphocytes is significantly smaller in molecular mass than syndecan from simple epithelia (85 vs 160 kDa) suggesting that syndecan may have distinct functions on these two cell types. Our study was undertaken to determine if syndecan mediates adhesion of B lineage cells to extracellular matrix. The murine myeloma cell line MPC-11 was used because syndecan is the only major heparan sulfate proteoglycan detected on these cells and because they express a form of syndecan almost identical to that found on normal B lymphocytes. Cell binding assays demonstrate that syndecan binds MPC-11 cells to type I collagen. Binding is inhibited by heparin, by pretreatment of cells with heparitinase or by growth of cells before the assay in chlorate, an inhibitor of sulfation. Solid phase assays show that syndecan purified from MPC-11 cells binds to type I collagen but not type IV collagen, laminin, or fibronectin. The interaction of MPC-11-derived syndecan with type I collagen is of relatively high affinity (Kd app = 143 nM) as measured by affinity coelectrophoresis. However, the 160-kDa form of syndecan isolated from epithelial cells has a greater than fourfold higher affinity for type I collagen (Kd app = 31 nM) than does the MPC-11 syndecan, suggesting that different molecular forms of syndecan have distinct ligand binding properties. These results demonstrate that syndecan can mediate B lymphocyte interactions with matrix and suggest that changes in syndecan expression during B cell differentiation are a mechanism for controlling B cell localization within specific microenvironments.

Animals↗
PubMed1985

The human tumor clonogenic assay in human breast cancer.

The human tumor clonogenic assay (HTCA) was evaluated in 407 fresh samples of breast cancer from 288 patients. Seventy samples were inadequate for testing. Adequate in vitro growth for drug testing (greater than 30 colonies/plate) was obtained in 91 (27%) of the 337 viable samples, inadequate growth for drug evaluation (5 to 30 colonies/plate) in 17%, and no colony formation (less than 5 colonies/plate) in 56%. Operationally defining a greater than or equal to 50% inhibition of colony formation as in vitro drug sensitivity, the in vitro response rates to 12 anticancer drugs tested against ten to 36 different cancers (arranged in decreasing order according to the number of tests performed) were as follows: doxorubicin (14%), bisantrene (54%), vinblastine (33%), mitomycin (36%), interferon clone A (23%), 5-fluorouracil (20%), methotrexate (17%), leukocyte interferon (33%), mitoxantrone (42%), cyclophosphamide (25%), m-AMSA (16%), and melphalan (10%). Among 25 patients receiving single-agent therapy, there were ten (59%) of 17 with in vitro sensitivity who responded; resistance was correctly predicted in nine patients (100%), P = .01. Among 34 patients treated with combination chemotherapy, seven (50%) of 14 with in vitro sensitivity responded, and resistance was predicted in 13 (65%) of 20 patients. Difficulties in using the HTCA in breast cancer (including small specimen size, difficulties in disaggregation, and inadequacy of growth) will require additional research. Nonetheless, the assay appears to detect in vitro activity as well as resistance of a variety of anticancer agents and appears to predict clinical responsiveness to standard as well as some investigational single agents.

Antineoplastic Agents↗
PubMed1984

Acquired inflammatory superior oblique tendon sheath (Brown's) syndrome. Report of a case following frontal sinus surgery.

A case of acquired Brown's syndrome secondary to fibrous proliferation about the trochlea and the superior oblique tendon developed following frontal sinus surgery. This syndrome is a restrictive ocular motility disorder characterized by vertical diplopia and inability to elevate the affected eye above the midline on medial gaze. The purpose of this report is to bring to the attention of otolaryngologists this sequela of sinus surgery, to offer suggestions for modification of surgical technique to avoid this complication, and to emphasize the importance of identifying any signs or symptoms of eye muscle dysfunction prior to surgery.

Adult↗
PubMed1983

Human myeloma in vitro colony growth: interrelationships between drug sensitivity, cell kinetics, and patient survival duration.

Ninety-seven patients with multiple myeloma evaluated serially had both a tritiated thymidine labeling index of bone marrow plasma cells (LI%) and in vitro myeloma stem cell culture performed. Thirty-three patients with myeloma colony growth had in vitro drug sensitivity testing carried out, 18 having in addition in vitro thymidine suicide determinations. The LI% and the likelihood of in vitro myeloma colony growth were highly correlated: the higher the LI%, the more likely was colony or cluster growth (p less than 0.001). The tritiated thymidine suicide of myeloma stem cells was usually very high. There was excellent correlation between in vitro and in vivo drug sensitivity. Both pretreatment drug resistance and selective sensitivity (e.g., interferon, bisantrene, methotrexate, vinblastine) at the time of relapse were accurately detected and correlated well with survival duration (p = 0.01 Wilcoxan). Although LI% and in vitro sensitivity were clearly independent variables, a high LI% (greater than 3%) plus in vitro resistance were associated with a subsequent survival duration of less than 6 mo. The studies allowed dissection of the complex interrelationship between cell kinetics and drug sensitivity.

Bone Marrow↗
PubMed1979

Dysthyroid ophthalmopathy: an update.

Since the original description of dysthyroid ophthalmopathy, much has been learned about its etiology, pathology, course, and management. The subject is reviewed in depth and the author suggests explanations relating to some of the poorly understood aspects of the disorder.

Eye Diseases↗