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Biomedical subjects

J Phillips

Publications and source records attributed to J Phillips.

At least 217 records · Page 12Linked to original sources
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

Altered expression of lymphocyte differentiation antigens on phorbol ester-activated CD4+8+ T cells.

Altered expression of cell surface Ag is an early event accompanying Ag-, mitogen-, or phorbol ester-induced activation of mature T cells. In this report, phorbol ester-induced changes in the expression of several functionally significant cell surface molecules are explored on immature thymocytes and lymphoma cells presenting a cortical CD4+8+ double-positive (DP) phenotype. Both CD4 and CD8 expressions are down-modulated on DP cells incubated with PMA. Cell-surface expression of CD4 and CD8 remains depressed for 72 h in the presence of PMA, but is restored after removal of PMA from the culture medium. The PMA-mediated loss of Ag expression is associated with a rapid down-regulation of steady state CD4 and CD8 mRNA transcript levels in treated cells. The sustained loss of CD4 and CD8 surface expression on DP cells is a selective event because CD5 expression is enhanced, H-2 expression is unchanged, and CD3 expression is only transiently diminished by PMA stimulation. Other T cell-activating agents, including Con A, ionomycin, and anti-CD3 mAb, induce selected surface antigenic changes on DP cells, but do not mimic the pattern of altered Ag expression observed after PMA stimulation. These data demonstrate that, similar to mature subsets, T cells in the DP nonmature compartment undergo alterations in expression of functionally important cell-surface molecules in response to activating agents. Nevertheless, distinctions between mature and nonmature T cells regarding specific alterations in differentiation Ag phenotype suggest that the effect of PMA on expression of these molecules depends, in part, on the maturation stage of the target cell population.

Adjuvants, Immunologic↗
PubMed1988

Expression pattern of a gene for a secreted metalloproteinase during late stages of tumor progression.

We have reported that transin RNA, a 1.9-kb RNA coding for a novel, secreted proteinase, was overexpressed during the progression of benign mouse skin papillomas to malignant squamous cell carcinomas (SCCs) induced by a two-stage protocol (Proc Natl Acad Sci USA 83:9413, 1986). Recently a high degree of similarity has been demonstrated between rabbit stromelysin, a secreted metalloproteinase that degrades proteoglycans found in the basement membrane and the amino acid sequence predicted in rat transin cDNA. DNA sequencing of a mouse cDNA isolated from an SCC (initiated by 7,12-dimethylbenz[a]anthracene [DMBA] and promoted by 12-O-tetradecanoylphorbol-13-acetate [TPA]) showed greater than 85% nucleotide similarity and 90% amino acid similarity to the rat transin-1 cDNA nucleotide and predicted amino acid sequences. Using this mouse transin cDNA clone as a probe (labeled with 32P) we found enhanced levels of transin mRNA transcripts in SCCs induced by a protocol giving rise to metastatic tumors (repeated N-methyl-N-nitroso-N'-nitroguanidine [MNNG] treatments) compared with the level found in SCCs induced by a protocol that had a lower probability of giving rise to metastatic tumors (MNNG initiation followed by TPA promotion). A study of primary SCCs and metastatic lesions induced by repeated benzo[a]pyrene treatment showed that the levels of transin mRNA transcripts were reduced in the metastatic lesions in comparison to the primary tumors. Southern analysis of the DNA isolated from epidermis, papillomas, and SCCs indicated that neither transin gene amplification nor rearrangement accounted for increased levels of the transin mRNA transcripts. These data suggest a role for enhanced levels of transin production in the invasion and metastasis of chemically induced SCCs.

9,10-Dimethyl-1,2-benzanthracene↗