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Biomedical subjects

J Phillips

Publications and source records attributed to J Phillips.

At least 37 records · Page 2Linked to original sources

First metatarsophalangeal joint reaction forces during high-heel gait.

First metatarsophalangeal (MTP) joint reaction forces were calculated for 11 normal females during the toe-off phase of gait while walking in bare feet and in high heeled shoes. A biomechanical model was used to calculate the forces utilizing kinematic, kinetic, footprint, and radiographic data. The results showed that the MTP joint reaction forces (FJ), the metatarsal-sesamoid forces (FS), and the resultant of these forces (FRES), were twice as large in high heels compared to barefoot walking. The average peak forces for barefoot and high-heeled gait were FJ: 0.8 and 1.58 times body weight, FS: 0.44 and 1.03 times body weight, and FRES: 0.93 and 1.88 times body weight. Also, the kinematics changed when wearing high heels, making angles of application of forces and sesamoidal articulations less favorable.

Adult

A phase I trial of taxol given by a 6-hour intravenous infusion.

Taxol is a unique mitotic inhibitor that has entered phase II investigation. Phase I studies demonstrated hypersensitivity reactions that were related to the cremophor vehicle and to the rate of drug infusion. As a result, the time span of intravenous (IV) infusion of taxol was routinely prolonged to 6 hours or beyond, and premedication with diphenhydramine, dexamethasone, and cimetidine was initiated. Early studies showed antitumor activity, especially against malignant melanoma and ovarian carcinoma. This phase I trial was performed giving taxol, as a 6-hour IV infusion every 21 days, without premedication. The purpose was to study the necessity of premedication and its impact on toxicity and pharmacokinetics. Thirty-one patients received 64 assessable courses of taxol. One patient had a hypersensitivity reaction, which was easily controlled using routine measures. Myelosuppression was dose-limiting, but sporadic, with two fatalities due to sepsis. Nonhematologic toxicity was of grade 1 and 2 except for one patient with grade 3 mucositis and two patients with grade 3 neuropathy. The neuropathy consisted of reversible painful paresthesias, requiring discontinuation of drug in two patients. Four partial responses were seen (three in patients with non-small-cell lung cancer, one in a patient with adenocarcinoma of unknown primary). Pharmacokinetic values were consistent with those previously reported. The occurrence of myelosuppression or neurotoxicity appeared to be associated with the area under the concentration x time curve (AUC) of taxol. The recommended phase II starting dose on this schedule is 225 mg/m2. Taxol merits broad investigation at the phase II level.

Alkaloids

Ethanol injection of hepatic tumors.

To assess the efficacy of intratumoral injections of absolute ethanol in the treatment of hepatic tumors, 18 New Zealand White rabbits underwent implantation of two 1-mm3 fragments of the VX-2 carcinoma. The animals were reexplored 2 weeks postimplant and the tumors measured. One nodule was treated by intratumoral injections of 2.28 +/- 0.72 mL of absolute ethanol; the second was injected with an equal amount of normal saline. The animals were sacrificed 4 weeks postimplant, and the tumors were measured and microscopically examined. On gross inspection, tumor size, expressed as the product of the largest and smallest diameters, was 4.59 +/- 3.4 cm2 for the ethanol-injected tumors vs 6.73 +/- 2.1 cm2 for the saline-treated nodules (p = .01). Histologic sections through the largest tumor diameter were microscopically examined using a computerized image analyzer. The mean cross-sectional area of viable tumor was 0.51 +/- 0.3 cm2 for the ethanol-treated nodules vs 2.01 +/- 0.5 cm2 for the saline-treated nodules (p less than .001). Contrast-enhanced CT and MRI studies were able to provide valuable information in terms of tissue characterization, which will be useful in differentiating viable tumor from necrotic tumor and infarcted liver. We conclude that intratumoral ethanol injection inhibits growth of liver tumors in this experimental model and deserves further study.

Animals

"Medical informatics in a medical research facility. An interactive multimedia presentation". Diabetes as a model.

This interactive demonstration provides a model for integrating information in a medical facility. By the use of networking computers, diagnostic data and scientific data are shared between geographically-separated clinical and research units. Data collected in a patient database in the outpatient clinic is sorted on specified qualifying criteria and the resulting subset further analyzed for research studies. To show the process of patient selection from a general database to a diabetes database, and further selection to a subset of diabetes, i.e., Diabetic Neuropathy, the authors used HyperCard. Firstly, HyperCard provided us with a flexible design allowing for both vertical and horizontal progressions. Because we wanted to include an educational component on diabetes and its complications, this flexibility was important. At any point in the demonstration, the viewer is able to access more information nested in several levels. Secondly, we wanted to be able to import a variety of programs that are used to translate diagnostic data into scientific data that is analyzed and prepared for publication in a medical textbook or journal. According to Douglas Adams, author of "Pathways and Relationships", HyperCard occupies the same niche in the evolution of software as human beings do in the evolution of life. "It's the fact that we are unspecialized but infinitely adaptable that has been our success as a species. In the same way, HyperCard is unspecialized but can turn its hand to any kind of task. And if the task is beyond it, HyperCard can use the phone, go for a ride on Excel, or go out and find a powerful graphics tool or sophisticated wordprocessing program!"

Academies and Institutes

Analysis of anticancer drugs in biological fluids: determination of taxol with application to clinical pharmacokinetics.

Taxol, a novel antimitotic, antitumor agent is currently undergoing Phase 1 clinical trials for the treatment of various tumors. An isocratic HPLC method has been developed for the determination of taxol in human plasma and urine. The method was then applied to the clinical pharmacokinetics of taxol following 6-h intravenous (i.v.) infusions at doses of 175 and 225 mg m-2. A mobile phase of methanol-acetate buffer (0.02 M, pH 4.5) (65:35, v/v) was used to elute a C8 column with detection at 227 nm. The sample preparation involved extraction with t-butyl methyl ether followed by further clean-up of the sample by solid-phase extraction. The method was linear from 0.10-10 microM injected, with a chromatographic run time of 6 min. The results obtained from the clinical study indicate that the plasma pharmacokinetics of taxol are best characterized by a two compartment open body model. Additionally, the present study resulted in the detection of a previously unreported peak which may be a metabolite of taxol.

Alkaloids

Fine needle biopsy of thyroid nodules: the importance of technique.

Fine needle biopsy (FNB) is the most accurate method available for the investigation of single thyroid nodules. The exact technique employed, however, varies considerably among clinicians: in our institution the incidence of 'inadequate' specimens produced ranges from only 13 to 62%, depending on the individual performing the biopsy. In a prospective in vivo study, a variety of biopsy techniques employing different gauge needles and differing numbers of passes with and without aspiration were assessed with respect to the quality of cytological specimen produced. Criteria assessed included the number of cells or sheets of cells, cell clumping, blood contamination, amount of colloid, and overall slide quality. Samples obtained with a 21 gauge needle without aspiration consistently gave best individual cell morphology. On the other hand, samples obtained with a 23 gauge needle with five aspirated passes through the nodule gave the highest yield of cells with an acceptable minimal increase in the degree of blood contamination and cell clumping. In order to achieve consistent yields from FNB of thyroid nodules, a combination of these two techniques is recommended.

Adult

Temporal movement control in patients with Parkinson's disease.

Patients with Parkinson's disease (PD) have been reported to be unable to modify their movement velocity to adapt to changing environmental demands. For example, when movement amplitude is varied, PD patients usually exhibit a nearly constant peak velocity, whereas elderly subjects show an increase of their peak velocity with increased amplitude. The experiment examined the ability of PD patients to vary the duration of their movement (four different percentages of their maximum) under conditions where temporal, but not spatial, control was emphasised. PD patients had longer movement times than control subjects, but were able to vary the duration of their movement with comparable temporal accuracy to that of elderly subjects. For both groups, the agonist EMG activity increased with decreased movement duration. For the PD patients, the number of agonist bursts increased with increased movement duration.

Aged

A rhesus monkey model for continuous infusion of drugs into cerebrospinal fluid.

A new rhesus monkey model with two intraventricular catheter systems was developed to examine the pharmacokinetics and neurotoxicity of chemotherapeutic agents administered by continuous intraventricular infusion. A lateral ventricular catheter system implanted in the lateral ventricle and attached to a subcutaneous access port on the animal's back is used for infusion of drugs into the ventricle. A Pudenz catheter implanted in the fourth ventricle and connected to a subcutaneous Ommaya reservoir permits repetitive CSF sampling in unanesthetized animals. The model was evaluated in five animals for over 12 months for catheter patency, surgical complications, and utility in studying the pharmacokinetics of continuous intraventricular infusion of methotrexate. There were no perioperative complications. Three of the five monkeys maintained both systems successfully. The other two animals developed staphylococcal ventriculitis, one at 7 days as a result of manipulation of the incision by the animal leading to cellulitis around the catheter site and subsequent ventriculitis, the other at 5 months. Both animals were treated successfully with antibiotics and catheter removal. An infusion of 0.05 mg of methotrexate over 24 hours maintained ventricular drug concentrations of 1 mol/L without evidence of neurotoxicity. This new model has applications both for the development of continuous intraventricular infusion as a therapeutic approach for the treatment of meningeal cancers in humans and as a research tool to study the distribution and elimination of drugs from the CSF.

Animals

Professional review and regulations.

New federal and state legislation will subject physicians to increasing scrutiny in the 1990s. This article highlights these new laws and explores physician concerns about them.

Confidentiality

Changes by two-dimensional echocardiography in the myocardial appearance of patients with end-stage renal disease.

A retrospective study of the clinical and biochemical data of all patients with end-stage renal disease who underwent 2-dimensional echocardiography at Tulane Medical Center between 1982 and 1986 was performed. Complete echocardiographic data were available for comparison in 53 patients. Highly reflective echoes were judged to be present in the myocardium of 81% of the patients. This characteristic is described as a "glistening speckled appearance." Patients with this characteristic had significantly greater left ventricular mass index (p = 0.0021).

Adult

Enhanced adrenocortical sensitivity to submaximal doses of cosyntropin (alpha1-24-corticotropin) in depressed patients.

There is evidence that excessive cortisol secretion in depressed patients might result, in part, from an enhanced adrenocortical sensitivity to corticotropin. This phenomenon has been examined using the cosyntropin (alpha1-24-corticotropin) stimulation test. Most studies have used supramaximal doses of cosyntropin administered in the morning, when adrenal sensitivity to corticotropin is at its maximum. This could partially obscure subtle differences in adrenocortical sensitivity in depression that might otherwise be evident at lower cosyntropin doses given later in the day. To test this hypothesis, we administered two consecutive cosyntropin tests on separate occasions employing a submaximal 0.05-microgram/kg dose and a maximal 0.2-microgram/kg dose. The cortisol centered cumulative response over 240 minutes was measured after each test in 12 depressed patients (7 melancholic, 5 nonmelancholic) and 6 healthy volunteers. When the difference in mean cortisol centered cumulative response values was determined, healthy controls demonstrated a significant increase in cortisol centered cumulative response, while the nonmelancholic patients had a less robust increase in cortisol centered cumulative response. In contrast, the melancholic patients demonstrated cortisol responses similar to those of the healthy subjects after each cosyntropin dose, suggesting an enhanced adrenocortical sensitivity to corticotropin. These data support the hypothesis that increased glucocorticoid secretion in depression may result from abnormalities at several sites within the hypothalamic-pituitary-adrenocortical axis.

Adrenal Cortex

The size of the hepatitis delta agent.

The size of the hepatitis delta virus was determined by filtration of infectious plasma through polycarbonate membranes and the inoculation of filtrates into chimpanzees. Chimpanzees inoculated with filtrates of 50 nm and 30 nm, but not 15 nm filters, developed delta hepatitis. The minimum size of infectious hepatitis delta virus was estimated to be approximately 30 nm, which is consistent with measurements of particles thought to be the virus.

Animals

Force production characteristics in Parkinson's disease.

This experiment examined the preparation and the production of isometric force in Parkinson's disease (PD). PD patients, elderly, and young subjects generated force levels that were a percentage of their maximum (15, 30, 45, and 60%). Subjects were cued on the upcoming target force level and they were asked to produce the required response as fast as possible. PD patients showed a similar progression of force variability and dispersion of peak forces to that of control subjects, implying they have an accurate "internal model" of the required forces. Force production impairments were seen, however, at the within-trial level. PD patients had more irregular force-time curves that were characterized by changes in the rate of force production. The results suggest a more "noisy" output from the motor system and an inability to produce smooth forces. PD patients were also substantially slower in initiating a force production and the delay was localized in the pre-motor reaction time.

Adolescent

Diagnosis of trisomy 18 in monozygotic twins by cordocentesis.

The incidence of monozygotic twins with trisomy 18 is 1 in 1,000,000 births. We report a case diagnosed prenatally with lymphocyte culture from fetal blood samples obtained by cordocentesis. Fetal growth lag and structural malformations detected by ultrasonography indicated chromosomal abnormality. A saline solution infusion technique ensured that cordocentesis obtained a sample from each twin.

Adult

Age, functional postural reflexes, and voluntary sway.

This experiment considered age-related changes in functional relationships between postural reflexes and voluntary movement. Young and older adults received horizontal perturbations during normal stance and when engaged in voluntary sway. Electromyographic activity showed that (a) older adults had poorer coordination between postural reflexes and voluntary movement, and (b) their stabilizing responses to postural disturbances during voluntary sway were slower. In addition, the onsets of activity of functionally important muscles were less tightly bilaterally coupled, and patterns of muscle onsets were less stereotypically organized in older adults. The results suggest that older adults experience some breakdown in the timing and sequencing of muscle activity and in the functional coordination of their postural reflexes with voluntary sway.

Adolescent

Phase I clinical investigation of amonafide.

Amonafide (benzisoquinolinedione, NSC 308847) is a new synthetic imide antineoplastic agent with DNA intercalative properties that has been evaluated in a phase I clinical trial. The drug was administered as a single intravenous (IV) infusion over 30 to 120 minutes repeated every 28 days. Ninety-five courses of therapy at doses ranging from 18 to 1,104 mg/m2 were administered to 38 patients with refractory solid tumors. Granulocytopenia was dose limiting. Leukopenia was seen in 13 of 31 courses at doses of 690 mg/m2 or greater. Life-threatening granulocytopenia (less than or equal to 250 microliters) was noted in 1/6 patients treated at 800 mg/m2, 1/8 patients treated at 918 mg/m2, and 2/5 patients treated at 1,104 mg/m2. No definite relationship between myelotoxicity and prior treatment status was noted. Rate-of-infusion dependent, nonhematologic toxicities included diaphoresis, flushing, dizziness, and tinnitus, all of which were ameliorated by increasing the duration of drug infusion to 120 minutes. In addition, nausea and vomiting (grades 1 and 2) were seen in 29/56 courses at doses greater than or equal to 519 mg/m2, but were easily controlled by phenothiazine antiemetics. Amonafide plasma and urine concentrations were determined by high-pressure liquid chromatography (HPLC). Plasma concentrations declined biexponetially with a terminal harmonic mean terminal half-life (t 1/2) of 5.5 h. The mean apparent volume of distribution at steady-state and total body clearance were 532 L/m2 and 84 L/h/m2, respectively. Less than 5% of the total dose of amonafide was excreted unchanged in the urine. Antitumor activity has been noted in one patient with non-small-cell lung cancer (one complete response exceeding 29 months duration) and in one patient with prostatic cancer (complete pain relief and improvement in bone scan for 9 months). The recommended dose for phase II trials with this schedule of amonafide is 918 mg/m2 with dose escalation to amonafide is 918 mg/m2 with dose escalation to myelotoxicity.

Adenine

Age related decline in postural control mechanisms.

In order to study voluntary and reflexive mechanisms of postural control, young and elderly persons were given large-fast and small-slow ankle-rotation postural disturbances while standing on a movable platform capable of measuring ground reaction forces. Large-fast rotations were employed to activate long-loop reflexes, and small-slow rotations were employed to tap the higher level sensory integration aspects of postural control. Overall, the elderly persons exhibited more perturbation induced sway and showed a slowing in voluntary, as opposed to reflexive mechanisms of correcting postural disturbance. For both age groups, reflexive mechanisms were found to be relatively intact. When small perturbations were given, the elderly persons swayed more than young participants and produced sporadic reflexive activity. Moreover, elderly persons did not adapt to the small perturbations and exhibited increased postural sway to repetitive presentation of the perturbation, whereas young participants substantially decreased their postural sway. These data demonstrate that elderly persons are at some disadvantage when posture is under the control of slower, higher level sensory integrative mechanisms.

Adult