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Biomedical subjects

D Phillips

Publications and source records attributed to D Phillips.

At least 181 records · Page 10Linked to original sources

5-Fluorouracil and methotrexate administered simultaneously as a continuous infusion. A phase I study.

Infusion delivery systems have been evaluated for administration of many individual chemotherapeutic agents including 5-fluorouracil (5-FU) and methotrexate (MTX). This study combined the two drugs as an admixture, and in a Phase I trial design established a useful dose schedule for each of the component drugs. 5-FU at a fixed dose rate of 300 mg/M2/day was delivered with methotrexate (MTX) at four different dose rates (0.75, 1.0, 1.5, or 2.0 mg/M2/day, respectively). The drug solution was delivered via a subclavian venous access with a portable infusion pump in an ambulatory setting. Twenty-nine patients received a total of 38 courses of the two-drug infusion: 21 courses were delivered with the two agents admixed constantly throughout treatment (Schedule A) and 17 were administered the treatment with 5-FU delivered continuously and MTX added to the 5-FU for alternate 14-day cycles (Schedule B). For the former schedule, dose-rate-limiting toxicity was related to MTX and included stomatitis developing at days 8 to 14 (median, day 8) with the higher dose rates (1.5-2.0 mg/M2/day) and thrombocytopenia developing at days 11 to 56 (median, day 14) at the lowest dose rates (1.0 mg/M2/day). For Schedule B, dose-rate-limiting toxicity was similarly due to the MTX with thrombocytopenia and/or chemical hepatitis developing in six of seven courses of MTX at 1.0 mg/M2/day and in five of ten courses delivered at 0.75 mg/M2/day. On Schedule B the MTX-associated toxicities were reversed when the MTX administration was interrupted and in the face of continued 5-FU infusion. A reasonable dose rate and schedule for continuous infusion of 5-FU combined with MTX is: 5-FU 300 mg/M2/day X 28 days and MTX 0.75 mg/M2/day for days 1 to 14, with cycles administered consecutively each 28 days.

Adult↗

Solvent relaxation in lipid bilayers with dansyl probes.

The solvent relaxation properties of the dansyl group attached to two lipids (dansylphosphatidylethanolamine and dansylphosphatidylserine), a fatty acid (dansylundecanoic acid), and two drugs (dansylbenzocaine and dansylpropranolol) were compared in a variety of different lipid systems. Several methods for characterising solvent relaxation were compared in detail for dansylpropranolol in bilayer vesicles of egg phosphatidylcholine. It was shown that the relaxation process is non-monoexponential; nevertheless, for comparative purposes, a model was adopted in which the lifetime associated with the negative exponent in a two exponential decay analysis, obtained at a particular energy on the red edge of emission, was taken as an approximation to a 'solvent relaxation' rate. A negative exponent, indicative of solvent relaxation processes, occurring in the nanosecond time-scale, was found only for dansylpropranolol, dansylPE and dansylundecanoic acid. On addition of the spin probe, 5-doxylstearate, the negative exponent was unaffected in liquid-crystalline phase lipids but was no longer found in gel-phase lipid in the case of dansylpropranolol, while for dansylPE the relaxation time was reduced. On the basis of these types of measurement it was possible to distinguish between different lipid environments using the same probe or between different dansyl environments of the different probes in the same lipid in cases where this would have been difficult or impossible solely on the basis of steady-state or fluorescence lifetime measurements.

Dansyl Compounds↗

Chlamydia trachomatis infection at a family planning clinic.

Endocervical samples were taken for the detection of Chlamydia trachomatis from 500 consecutive patients attending a family planning clinic. The Microtrak direct specimen immunofluorescence test was used. Swabs from 79 patients (15.8%) were positive for chlamydia. Seventy-one (95%) of these patients were symptom free, and 39.8% were under 20 years old. Twenty-one patients were pregnant, seven (33%) had chlamydia. Those positive for chlamydia had twice the frequency of abnormal smears and other sexually transmitted infections as those who were negative. Contraceptive use was similar except that intrauterine devices were used less frequently by patients with chlamydia infection. This report indicates the frequent occurrence of Chlamydia trachomatis infection in New Zealand and that newly developed methods of diagnosis enable us to identify and treat those with this infection. Characteristically these patients are under 20, have multiple partners and a high incidence of abnormal smears and other sexually transmitted infections.

Adolescent↗

Natural experiments and the educational context: the environment and effects of an alternative inner-city public school on adolescents.

The 1-year impact of attending a public alternative high school on two cohorts of adolescents who gained entrance to the school through a lottery was studied. Adolescents who had applied to the school but were not selected in the lottery served as a control group. The nature of the alternative high school environment is described, and the outcome of this natural experiment defined in terms of reactions to school, attitude change, and student achievement. In general, the alternative school positively affected student satisfaction with a variety of aspects of school life and induced some positive change in interracial attitudes while not harming student achievement. Race effects were found in the areas of achievement and interracial attitudes. Implications for the study of natural experiments in general and the specific data in particular are drawn.

Achievement↗

Neuromuscular adaptation of craniofacial muscles to altered oral sensation.

Experimentally induced changes in oral sensation to the tongue altered the use of specific craniofacial muscles. An acrylic wedge was anchored to the maxillary teeth of ten adult rhesus monkeys, providing a tactile-pressure sensation to the dorsal surface of the tongue. Fifteen craniofacial and tongue muscles were studied by electromyography during the first 6 months of adaptation. The results showed that there was an overall shift in those muscles that were normally tonically active in the craniofacial region. Muscles of the suprahyoid region, the geniohyoid and digastric, as well as the platysma muscle of the face, and the lateral pterygoid muscle were tonically active in more animals after placement of the wedge. In contrast to the enhanced activity of mandibular and facial muscles that function during mandibular depression, only the anterior temporalis muscle in the superficial and deep region demonstrated more tonic activity. The superficial and deep masseter regions, as well as the medial pterygoid muscle, demonstrated no change in their EMG activity. Only the lip muscles and mentalis demonstrated increased activity, whereas the facial muscles with more vertically oriented fibers did not demonstrate any increased activity. These findings suggest that a change in the tactile stimulation to the tongue can induce a new balance in the level of activity of specific craniofacial muscles and that this altered neuromuscular pattern can remain throughout the first 6 months of adaptation.

Adaptation, Physiological↗

Effect of bronchial lavage volume on cellular and protein recovery.

To investigate the optimal lavage technique to study the airway response in patients with asthma, differential volume lavage was carried out in 22 normal subjects and 18 patients with red cedar asthma. Ten ml of fluid was instilled into a main-stem bronchus followed by 5, 10, 20, 50 and 100 ml into different segmental bronchi. Small volume lavage (less than 20 ml) in a main stem bronchus or a segmental bronchus recovered more epithelial cells and neutrophils while a lavage volume of 20-100 ml in a segmental bronchus recovered more lymphocytes, alveolar macrophages, albumin, IgG and alpha 1-antitrypsin. In patients with asthma, a higher proportion of epithelial cells was observed in the 20 ml segmental bronchus lavage 24 to 48 hours after bronchial challenge with plicatic acid, the chemical compound responsible for red cedar asthma. There was an increase in eosinophils and IgG with all volume lavages, but the changes were most marked in the 10 ml main bronchus lavage and the 10 and 20 ml segmental bronchus lavage. The results show the importance of using a systematic lavage protocol to characterize the cellular and protein changes in the airways of patients with asthma. A single volume lavage in one site may not encompass all the changes observed.

Adolescent↗

The effects of denturism on denture prices.

In 1978, the country's first denturism initiative was passed in Oregon, legalizing the independent construction of dentures by non-dentists. The major campaign issue was the effect denturism would have on the cost of dentures. A review of Oregon dental insurance data shows that the costs of dentures, which had been rising at the same rate as other dental services, had a much lower rate of increase after passage of the denturism initiative.

Dental Auxiliaries↗

TMJ syndrome.

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Humans↗

Picosecond spectroscopy: applications in biochemistry. Part I: Techniques.

A number of sources of picosecond optical pulses and the means by which they may be used to investigate fast molecular processes have been described. In addition, it should be pointed out that most of these techniques can be extended to take advantage of other properties of the laser pulses; in particular, the polarization is of use in measuring time-dependent antisotropy. The state of the art is now the generation of 30fs pulses; it seems likely that this is all the time resolution that one is likely to need for investigating biological and other molecular processes as at such short times the uncertainty principle leads to a considerable loss of spectral resolution.

Argon↗

The illusion of incompetence among academically competent children.

To assess the relation between children's perceptions of cognitive competence and their achievement orientations, a group of 117 academically competent fifth graders and their teachers were administered a battery of questionnaires tapping a variety of motivational constructs. The children were then divided into low, average, and high groups on the basis of subscale scores on a standardized measure of perceived cognitive competence. Approximately 20%--equal proportions of girls and boys--had self-perceptions that seriously underestimated their actual high abilities. When compared to the children whose self-perceptions were commensurate with their abilities, the children with low perceived competence were shown to adopt lower standards and expectancies for success, to perceive that their teachers expected less of them (confirmed by the teachers' expectancy ratings), to rank unstable effort as a more important cause of their high grades than ability, and to be portrayed by their teachers as lacking in persistence. Very few sex differences emerged. Several theoretical issues are raised regarding the early acquisition, perpetuation, causal significance, and behavioral manifestations of inaccurate and disparaging self-perceptions among young children.

Achievement↗

Patterns of mortality in homes for the elderly.

High rates of mortality are an abiding feature of homes for the elderly. Almost a fifth (19.2%) of a cohort of 6947 residents died in the 12 months following initial assessment. Survival rates vary widely, however, for different groups within the residential population. Using data from a longitudinal study of 175 homes for the elderly, this paper examines the relationship between mortality, age, length of stay, and dependency. The interaction between these variables within the residential setting helps to identify the 'high risk' groups of residents who require special surveillance and care.

Activities of Daily Living↗

Endogenous protein carboxyl methylation in hamster spermatozoa: changes associated with capacitation in vitro.

Protein carboxyl methylase (PCM) and its substrate(s), methyl acceptor protein(s) (MAP), are present in the spermatozoa of rat, rabbit and man. In the present study, PCM activity and MAP capacity were measured in homogenates of hamster testes and isolated spermatozoa, and found to be similar to those of other species. Using solubilized preparations of spermatozoa from the cauda epididymis of hamster, PCM activity was twice as high in sperm tails as in heads while the reverse was true for MAP capacity. Since in this and in previous studies this enzyme reaction has been measured in broken cells, we thought it pertinent to measure methylation under physiological conditions (i.e., in motile spermatozoa). To accomplish this, an assay was developed which depends upon the conversion of [3H-methyl]methionine to S-adenoxyl-L [methyl-3H]methionine which, in turn, serves as a methyl donor for PCM. In sperm that had been labelled with [3H]methionine the MAP for the endogenous methylation reaction was not solubilized with Triton X-100, and was found primarily in sperm tails. When hamster spermatozoa were incubated in medium containing taurine, epinephrine and bovine serum albumin to induce capacitation, endogenous methylation was stimulated 8- to 9-fold; when taurine was omitted from this medium, methylation was stimulated 14-fold. Taurine, however, was essential for in vitro fertilization as the number of eggs fertilized declined from 92% in complete medium to 0% in medium minus taurine. The decrease in fertilization rate was also associated with a decrease in sperm motility. In previous studies we have demonstrated an association between PCM and sperm motility, and have suggested that this enzyme system could be involved in other functions such as the acrosome reaction. From the results in the present study we conclude that the conditions that lead to capacitation in vitro are associated with a marked change in endogenous protein carboxyl methylation.

Animals↗

Corticosteroid modulation of the renin system and blood pressure in the spontaneously hypertensive rat.

This study examines the role of gluco- and mineralcorticoids in the regulation of the renin-angiotensin system and blood pressure in the spontaneously hypertensive rat (SHR). Effects of adrenalectomy and selective treatment with either aldosterone (30 micrograms/kg/day) or dexamethasone (60 micrograms/kg/day) on plasma renin substrate, active renin (PRA), total renin and blood pressure were studied in 10 week old SHR and control WKY rats. Systolic blood pressure was moderately lower in adrenalectomized rats (129 +/- 2 mm Hg vs 137 +/- 4 mm Hg in control WKY and 145 +/- 4 mm Hg vs 160 +/- 3 mm Hg in control SHR) but could be restored to the control range by aldosterone. Dexamethasone repletion induced substantial increments of systolic blood pressure to comparable levels in both species (202 +/- 8 mm Hg in WKY and 192 +/- 6 mm Hg in SHR). Renin substrate was markedly lower in adrenalectomized, saline repleted rats. This could be reversed by dexamethasone in both species and by aldosterone in WKY rats only. Both PRA and total renin were higher (p less than 0.01) in the adrenalectomized, saline repleted state. This increase was not observed in aldosterone repleted rats. However, dexamethasone inhibited the adrenalectomy associated increase of PRA and total renin in SHR but not in WKY rats. Differences in blood pressure between SHR and WKY persist even in adrenalectomized state despite comparable stimulation of the renin system. Conversely, while blood pressure of both species responds similarly to selective corticosteroids therapy, the response of the renin-angiotensin system in SHR and WKY rats is distinct. Therefore factors other than the adrenal gland and the renin system must be involved in the determination of the high blood pressure in SHR.

Adrenal Cortex Hormones↗

Effect of metoclopramide and domperidone on aldosterone, 18-hydroxycorticosterone and prolactin secretion in the rhesus monkey.

This study was designed to investigate dopaminergic mechanisms in the control of corticosteroid secretion. Eight rhesus monkeys received metoclopramide (200 micrograms/kg) or domperidone (200 and 400 micrograms/kg) with 5% dextrose (vehicle), or with dopamine (4 micrograms/kg/min) infusions begun 60 min before administration of the dopamine antagonist. Metoclopramide, in the presence of vehicle, increased plasma aldosterone concentrations from 4.8 +/- 0.6 ng/dl to a maximum of 36 +/- 4.7 ng/dl and PRL concentrations from 7.6 +/- 1.1 ng/ml to a maximum of 120.5 +/- 8.0 ng/ml. Administration of metoclopramide resulted in a rise in plasma 18-hydroxycorticosterone from 10.2 +/- 1.3 ng/dl to a maximum concentration of 49.6 +/- 4.5 ng/dl. Plasma concentrations of electrolytes, PRA, plasma cortisol, 11-deoxycorticosterone, corticosterone, 18-hydroxy-11-deoxocorticosterone, were not altered by metoclopramide. Domperidone, in both doses, markedly increased plasma PRL concentrations but had no effect on plasma 18-OHB or aldosterone concentrations. Dopamine infusion inhibited the aldosterone response to metoclopramide and the prolactin response to metoclopramide and domperidone. The results of this investigation demonstrate that aldosterone responses to metoclopramide and prolactin responses to metoclopramide and domperidone are mediated by their antagonist activity at dopamine receptors.

18-Hydroxycorticosterone↗