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Biomedical subjects

D Thornton

Publications and source records attributed to D Thornton.

At least 19 recordsLinked to original sources
PubMed1998

Particle nucleation in the tropical boundary layer and its coupling to marine sulfur sources

New particle formation in a tropical marine boundary layer setting was characterized during NASA's Pacific Exploratory Mission-Tropics A program. It represents the clearest demonstration to date of aerosol nucleation and growth being linked to the natural marine sulfur cycle. This conclusion was based on real-time observations of dimethylsulfide, sulfur dioxide, sulfuric acid (gas), hydroxide, ozone, temperature, relative humidity, aerosol size and number distribution, and total aerosol surface area. Classic binary nucleation theory predicts no nucleation under the observed marine boundary layer conditions.

Journal Article↗
PubMed1998

Tangential irradiation of the intact breast: the ABC of the technique.

This paper describes in detail the setup of breast irradiation using an isocentric tangential technique. This setup method does not require any special devices or calculations beyond simple arithmetic. We will discuss some of the practical problems and pitfalls that result from the oblique incidence of the radiation beams and the slope of the chest wall and provide possible solutions.

Breast Neoplasms↗
PubMed1997

Adequate irradiation of the internal jugular lymph node chain: technical considerations.

PURPOSE: This research aimed to study the anatomic relationship between the internal jugular vein with the surrounding internal jugular lymph node chain and the underlying bony anatomical structures which are commonly used as landmarks for radiation therapy planning. METHODS AND MATERIALS: Twelve patients with carcinoma of the head and neck region were studied prospectively. Using our three-dimensional planning system, a beam's-eye view of the internal jugular vein was projected onto a lateral and anterior simulation film. Quantitative measurements were made in every case of the anatomic relationship between the internal jugular vein and the posterior border of the cervical vertebrae and sagittal midline. RESULTS: The distance between the posterior border of the internal jugular vein and the posterior border of the cervical vertebrae ranged between 0 and 2.5 cm. The distances between the sagittal midline and the medial border of the internal jugular veins ranged between 2 and 4 cm. CONCLUSION: To ensure adequate irradiation of the internal jugular lymph nodes, the posterior border of the lateral radiation therapy upper-neck fields should be placed at least 1 cm posterior to the posterior aspect of the cervical vertebrae. The midline block used in the lower neck anterior field should not exceed 2 cm in width.

Cervical Vertebrae↗
PubMed1996

Regulation of murine osteoblast macrophage colony-stimulating factor production by 1,25(OH)2D3.

Macrophage colony stimulating factor (MCSF) is important for formation of osteoclasts. We investigated the ability of 1,25(OH)2D3 to regulate osteoblast production of MCSF. Mouse calvarial osteoblasts were cultured for 2 days +/- 1,25(OH)2D3. Since 1, 25(OH)2D3 decreased osteoblast proliferation by 17.6 +/- 1% at 10 nM and 11 +/- 4% at 1 nM, the effect of growth rate on MCSF secretion was examined. Limiting cell proliferation by serum did not affect MCSF production. 1,25(OH)2D3 (1 nM) increased MCSF production (U/10(5) cells) maximally by 68 +/- 33% (n = 3) with an ED50 for 1, 25(OH)2D3 of 5 x 10(-11) M. To investigate effects of 1,25(OH)2D3 on MCSF gene regulation, RT-PCR primers were designed to identify the mRNA coding for the membrane-bound isoform of MCSF. Simultaneous RT-PCR of glyceraldehyde-phosphate dehydrogenase (GAP) allowed semiquantitative assessment of MCSF mRNA between treatment groups expressed as the MCSF/GAP RT-PCR product ratio; both MCSF and GAP (+) primers were labeled with 32P-ATP for phosphorimage quantitation. The membrane-bound MCSF/GAP PCR product ratio was not affected by proliferative rate when growth was limited by [serum]. The MCSF/GAP RT-PCR product ratio was dose dependently increased by 1,25(OH)2D3, maximally at 1 nM at 2.2 +/- 0.2 = fold (n = 10). 1,25 (OH)2D3 also increased the expression of an RT-PCR MCSF/GAP product ratio which represented the secreted isoform of MCSF. The ability of 1,25(OH)2D3 to pretranslationally regulate expression of membrane-bound osteoblast MCSF may be important in osteoblast:osteoclast interactions.

Animals↗
PubMed1996

Radiotherapy for early infradiaphragmatic Hodgkin's disease: the Australasian experience.

PURPOSE: To review the Australasian results of Stage I and IIA Infradiaphragmatic Hodgkin's Disease (IHD) treated solely by irradiation. METHODS AND MATERIALS: Eligible patients had IHD only and were treated by irradiation with curative intent over the period of 1969 to 1988. Ten radiation oncology centres from within Australia and New Zealand were surveyed for patient, tumour and treatment variables. Disease free rates, survival and complications were analysed. RESULTS: 106 patients with IHD were studied. The average potential follow up was 9.4 years. The male to female ratio was 3.3:1. The median age was 37.5 years. Histological subgroups were as follows; lymphocyte predominant 43%, mixed cellularity 21%, lymphocyte depleted 5%, nodular sclerosing 27% and unclassifiable 4%. Fifty nine patients had laparotomy of which 22 (37%) were positive for tumour. Nine laparotomies were performed for diagnosis and the remainder for staging. One patient was up-staged by laparotomy and three were down-staged. Sixty-eight patients presented with inguinal disease alone, five with abdominal disease alone, 19 with two sites of involvement and 12 with inguinal, pelvic and abdominal disease. In two patients the site was unknown. There was no correlation between site of involvement, age, sex or histological subtype. Forty seven cases were clinically staged (CS) as follows: CS IA-23, CS IIA-24. The other 59 were pathologically staged (PS) as follows: PS IA-37, PS IB-1, PS IIA-21. Treatment consisted of involved field alone (16), inverted Y (68), inverted Y and spleen (13), para-aortic irradiation only (3), or total nodal irradiation (6). Mean dose was 37 Gy. There were 30 recurrences to give an acturial 10-year disease-free rate of 70%. In multivariate analysis lower number of tumour sites, lymphocyte predominant histology and higher dose were all significantly correlated with higher disease free rates. Eight patients died of Hodgkin's disease and 19 of other causes. The 10-year overall survival rate was 71%. Older age and higher number of disease sites were significantly correlated with shorter survival. Fourteen of 30 relapses may have been avoidable by the use of total nodal irradiation. In particular ten of 21 patients with abdominal disease relapsed in nodal sites which would have been covered by total nodal irradiation. CONCLUSIONS: The rate of control in IHD could perhaps be improved by avoiding involved field irradiation or by aggressive therapy with total nodal irradiation or combined modality chemo-irradiation in Stage II disease. Staging laparotomy does not appear to be indicated.

Abdominal Neoplasms↗
PubMed1995

Synthesis and structure-activity relationships of phenylenebis(methylene)-linked bis-tetraazamacrocycles that inhibit HIV replication. Effects of macrocyclic ring size and substituents on the aromatic linker.

We have previously described the potent and selective inhibition of several strains of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) by JM2763, an n-propyl-linked dimer of the 1,4,8,11-tetraazamacrocyclic (cyclam) ring system. Upon further investigation, we have also found that incorporating an aromatic rather than aliphatic linker leads to analogs with higher antiviral potency. The prototype, JM3100 (19a, isolated as the octahydrochloride salt), which contains a p-phenylenebis(methylene) moiety linking the cyclam rings, inhibited the replication of HIV-1 (IIIB) and HIV-2 (ROD) at EC50's of 4.2 and 5.9 nM, respectively, while remaining nontoxic to MT-4 cells at concentrations exceeding 421 microM. In order to identify the structural features of bis-tetraazamacrocycles required for potent activity, we have prepared a novel series of phenylenebis(methylene)-linked analogs, in which the macrocyclic ring size was varied from 12 to 16 ring members. Depending upon the substitution of the phenylenebis(methylene) linker (para or meta), sub-micromolar anti-HIV activity was exhibited by analogs bearing macrocycles of 12-14 ring members but with varying cytotoxicity to MT-4 cells. Furthermore, while we found that identical macrocyclic rings are not required for activity, substituting an acyclic polyamine equivalent for one of the cyclam rings in 19a resulted in a substantial reduction in anti-HIV potency, clearly establishing the importance of the constrained macrocyclic structure. A short series of transition metal complexes of 19a were also prepared and evaluated. Complexes of low kinetic stability such as the bis-zinc complex retained activity comparable to that of the parent compound. Finally, the activity of bicyclam analogs appears to be insensitive to the electron-withdrawing or -donating properties of substituents introduced onto the linker, but sterically hindering groups such as phenyl markedly reduced activity. As a result, several analogs with anti-HIV potency comparable to that of 19a have been identified.

Antiviral Agents↗
PubMed1994

The FGF-4 promoter is required for transformation and is active in both embryonal and somatic cells.

We report the independent isolation of a rearranged FGF-4 gene from a patient with chronic myeloid leukaemia. We show that the FGF-4 gene has been truncated 30 nucleotides 3' to the coding sequence and has been fused to the RNA processing signals from a putative unknown gene on chromosome 15. We demonstrate that the promoter region of the FGF-4 gene is active in NIH3T3 cells and is indeed necessary for transformation. Using the luciferase reporter assay we have shown that the FGF-4 5' flanking sequences possess easily detectable promoter activity in both F9 and HeLa cell lines. 5' deletion analysis of the FGF-4 promoter has delineated regions containing cis-acting elements of functional importance. These regulatory regions are common to both embryonal and somatic cell lines. Electrophoretic mobility shift assay, using nuclear extracts from F9 and HeLa cells, has allowed detection of DNA-protein interactions occurring in the functionally significant regions. Subsequent comparison of the human and murine FGF-4 promoters show that the regions of functional significance are highly conserved. We suggest that the FGF-4 gene may be suppressed through a distal suppressor locus and becomes active when separated from this suppressor.

3T3 Cells↗
PubMed1992

Magnetic field exposure assessment for adult residents of Maine who live near and far away from overhead transmission lines.

Sixty-Hz magnetic field exposures were measured for 45 adult residents of Maine. Thirty of the subjects resided near rights-of-way (ROWs) with either 345- and 115-kV transmission lines, or ROWs with only 115-kV transmission lines; fifteen resided far from any transmission lines. Personal exposure data for a single 24-hour period was acquired with the EMDEX. The EMDEX's event-marker button was used to partition exposures into Home and Away components. Also, three area measurements were taken for each subject during the personal exposure measurement period: 1) 24-hr fixed-site bedroom measurement with a second EMDEX; 2) Spot measurements in at least three rooms of every residence; and 3) Spot measurements outside each residence. Residence near transmission lines highly loaded during the measurement period was associated with increased Home and Total exposure relative to a far-away population. Average exposure level while away from home was uniform (at about 2 mG) throughout the study population. On a quantitative level, Home exposure was correlated equivalently with Spot-In (r = .70) and the 24-hr fixed site measurement (r = .68). Correlations of area measurements with Total exposure were weaker because of the dilution effect of Away exposure (r = .64 for Spot-In; r = .61 for 24-h Bedroom). Away and Home exposures were not correlated (r = .14), which reinforced our confidence that the participants used the EMDEX correctly. The data suggest the need for caution before inferences are drawn about total personal exposure from area measurements. The study demonstrates the feasibility of obtaining valid measures of magnetic-field exposure with the personal exposure monitors that have been developed.

Adult↗
PubMed1992

Acute effect of consumption/omission of breakfast on exercise tolerance in adolescents.

The purpose of this study was to determine the acute effects of the consumption or omission of breakfast on exercise tolerance in adolescents. Physically active adolescents (14 males and 21 females) were randomly assigned to receive a breakfast (B) or placebo (P) after an overnight fast. Exercise tolerance tests were done 1.5 hours (test 1) and again 4 hours (test 2) after consuming B or P and consisted of cycling on a stationary bike for 4 minutes at each of four consecutive power settings: 25, 50, 75, and 100 watts. Blood glucose and beta-hydroxybutyrate concentrations were measured before both tests. VO2 and VCO2 were measured during minute 3 of cycling at loads 50 and 75 watts and were used to compute the respiratory exchange ratio (RER). Heart rates (HR) were monitored throughout the test and ratings of perceived exertion (RPE) were made at the end of each 4 min interval. Repeated measures ANOVA revealed that there were no differences in RPE; however, differences for HR and RER did exist. Mean RER values were higher for the males receiving B vs males receiving P during test 1. For females, HR were higher for P compared B, and beta-hydroxybutyrate was significantly elevated for P before test 2. The data suggest that exercise tolerance as indicated by the ratings of perceived exertion are unaffected by prior ingestion of a breakfast but breakfast does affect the physiologic responses to exercise.

Adolescent↗
PubMed1989

Psychosocial determinants of compliance in adolescents with iron deficiency.

The relationship between selected psychosocial variables and compliance was studied in 71 adolescents prescribed medication for iron deficiency. The mean compliance rate in the study group was 67%. Home pill counts were highly correlated with the other methods of measuring compliance, ie, change in serum ferritin level and urinary assay for tracer riboflavin. Statistically significant predictors of compliance included adverse side effects, initial estimate by the adolescent as to his probable level of compliance, and frequency of family reminders to take the medication. There was no significant correlation between self-esteem, locus of control, or most variables of the Health Belief Model and the level of patient compliance. Our findings suggest that home pill counts are an accurate method of assessing compliance and that instituting family reminders may be helpful in those adolescents who are potentially non-compliant.

Adolescent↗
PubMed1989

Pharmacodynamics of thrombolysis with recombinant tissue-type plasminogen activator. Correlation with characteristics of and clinical outcomes in patients with acute myocardial infarction. The TAMI Study Group.

Coagulation analysis was performed on blood samples from 386 patients with acute myocardial infarction drawn before, during, and after a continuous intravenous infusion of 150 mg recombinant tissue-type plasminogen activator (rt-PA) (Activase). Plasma rt-PA rose to peak levels of 2.1 +/- 3.1 micrograms/ml (mean +/- SD). Fibrinogen levels measured by coagulation rate and by sulfite precipitation decreased from baseline levels of 3.0 +/- 0.9 and 3.2 +/- 1.0 g/l, respectively, to nadir levels of 1.4 +/- 0.75 and 1.8 +/- 0.92 g/l, respectively, and were associated with peak levels in serum of fibrinogen-degradation products (FDP) of 230 +/- 470 micrograms/ml. Forty percent of patients experienced a nadir functional-fibrinogen level of less than 1.0 g/l, whereas 20% fell below 0.5 g/l. Nadir fibrinogen levels did not correlate with patency of the infarct-related coronary artery at 90 minutes or with risk of coronary vessel reocclusion within 7-10 days. However, the risk of coronary artery reocclusion was inversely related to the baseline functional fibrinogen level (p = 0.0008), with the magnitude of its drop to nadir level (p = 0.0003) as well as to peak levels of FDP (p = 0.038). Quantitative blood loss correlated with all markers for systemic fibrinogenolysis including nadir fibrinogen level (r = -0.20, p = 0.0011), percent decrease of fibrinogen (r = 0.22, p = 0.001), and peak FDP levels (r = 0.14, p = 0.020). Both patients who experienced intracranial hemorrhage presented with high baseline fibrinogen levels and experienced extensive degradation of coagulable fibrinogen. Overall, patients at greatest risk of systemic fibrinogenolysis tended to be relatively older women with lower body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗
PubMed1988

Laboratory monitoring of hemostasis during thrombolytic therapy with recombinant human tissue-type plasminogen activator.

Recombinant tissue-type plasminogen activator (rt-PA) was administered intravenously to 93 patients with acute myocardial infarction and coronary thrombosis in doses of 30 to 150 mg over 1.5 to 6 hours. During this infusion plateau levels of rt-PA in plasma ranged between 0.4 and 2.2 micrograms/ml. Activation of the plasma fibrinolytic system and fibrinogen breakdown both in vivo and in vitro was observed with this therapy. In vitro fibrinogenolysis in plasma was more effectively prevented by collection of blood samples on aprotinin (200 kallikrein inhibitor units/ml blood), a conventional serine protease inhibitor, than on either of two monoclonal antibodies against t-PA (200 micrograms/ml plasma), or on D-phenylalanyl-prolyl-arginine-chloromethyl ketone (PPACK), a newly developed synthetic inhibitor of t-PA. Results of fibrinogen measurements during infusion of rt-PA were dependent on the method of assay. In a subgroup of 36 patients after completion of a thrombolytic infusion, fibrinogen decreased in vivo by 27% when measured as total coagulable protein and by 33% with a coagulation rate assay, but increased by 26% with an automated assay system. The extent of fibrinogenolysis was proportional to the plasma level of rt-PA but substantial intersubject variation was observed. Fibrinogenolysis in vivo was also associated with alpha 2-antiplasmin depletion and was more pronounced with a two-chain (G11021) than with a single-chain preparation (G11035) of rt-PA.

Fibrinogen↗
PubMed1988

Efficacy of oral sucralfate suspension in prevention and treatment of chemotherapy-induced mucositis.

The efficacy of orally administered sucralfate suspension in preventing and treating chemotherapy-induced mucositis was evaluated in a double-blind trial. Forty-eight children and adolescents with newly diagnosed acute nonlymphocytic leukemia were randomized to receive suspensions of either sucralfate or placebo orally every 6 hours during the first 10 weeks of intensive remission-induction chemotherapy. Patients given sucralfate suspension were less likely than subjects receiving placebo to acquire colonization with potentially pathogenic microorganisms: 14 (58%) of 24 versus 22 (92%) of 24, respectively (p = 0.008). However, no effect on preexisting colonization was noted. Subjective reporting of discomfort, objective scoring of the severity of mucositis, and the maximal percent of body weight lost during therapy were similar; 58% of patients receiving sucralfate reported no oral pain compared with 25% receiving placebo (p = 0.06). Ten episodes of gastrointestinal bleeding, 25 documented infections, and 886 days with fever were also equally distributed between sucralfate and placebo groups. We conclude that sucralfate suspension is of limited, if any efficacy, in the prevention and treatment of chemotherapy-induced mucositis. Sucralfate administration can, however, reduce acquisition of alimentary colonization with potential pathogens, perhaps by interfering with adherence to mucosal membranes.

Administration, Oral↗
PubMed1987

Successful intermittent chemoprophylaxis for Pneumocystis carinii pneumonitis.

We conducted a prospective, randomized clinical trial over a two-year period in patients with acute lymphocytic leukemia to assess the effectiveness of trimethoprim-sulfamethoxazole given on three consecutive days each week as compared with daily in the prevention of Pneumocystis carinii pneumonitis. P. carinii pneumonitis did not develop in any of 92 patients receiving the drug daily (30,602 patient-days) or in any of 74 who received it three consecutive days a week (27,329 patient-days), whereas the incidence of the infection expected without prophylaxis is 21 percent. One patient, excluded from both groups because of an adverse reaction to sulfonamides in the past, acquired P. carinii pneumonitis. Especially noteworthy was a difference in the occurrence of systemic mycoses, with 10 cases in the daily-treatment group and only 1 case in the three-days-a-week group (P = 0.024). No differences were observed in the rates of other infections or adverse effects associated with the drug. We conclude that trimethoprim-sulfamethoxazole is as effective given three days a week as it is given daily in the prevention of P. carinii pneumonitis and that the intermittent schedule has the advantages of less frequent fungal infections and lower cost. Intermittent chemoprophylaxis may be especially beneficial to certain patients who are unable to tolerate the daily doses.

Anti-Infective Agents↗
PubMed1987

Induction of prostaglandin synthesis as the mechanism responsible for the chills and fever produced by infusing amphotericin B.

Amphotericin B produces chills and fever in a significant proportion of patients who receive this drug. The mechanism for this adverse effect is unknown. Amphotericin B suspension at a concentration of 1.0 microgram/ml was demonstrated to be a potent inducer of prostaglandin E2 synthesis by human and murine mononuclear cells in vitro. A double-blind, placebo-controlled clinical trial demonstrated that ibuprofen (10 mg/kg), a potent inhibitor of prostaglandin synthesis, administered 30 min before amphotericin B administration reduced the incidence of chilling from 87% to 49% (P = .01); the incidence of chilling reactions considered severe was reduced from 69% to 15% (P = .008). We postulate that the chills and fever produced by an infusion of amphotericin B are mediated through prostaglandin E2 synthesis. Ibuprofen is therapeutically useful in ameliorating the chills and fever caused by amphotericin B.

Adolescent↗