Search PubMedSearch

Biomedical subjects

M Phillips

Publications and source records attributed to M Phillips.

At least 55 records · Page 3Linked to original sources

False positive seroreactivity to Borrelia burgdorferi in systemic lupus erythematosus: the value of immunoblot analysis.

UNLABELLED: The object of this study was to determine the incidence of seropositivity to B. burgdorferi by the commonly available enzyme-linked immunosorbent assay (ELISA) in patients with SLE and other rheumatic diseases and to evaluate immunoblot analysis as a tool to differentiate true from false positive ELISA. Sera were obtained from patients with SLE (n = 35), rheumatoid arthritis (n = 26), seronegative arthritis (n = 28) and Lyme disease (n = 18). Reactivity to B. burgdorferi antigens was analysed by two available diagnostic techniques: ELISA and immunoblot. Correlations were made between seroreactivity to B. burgdorferi and standard serological tests of autoimmunity: antibodies to nuclear antigens, dsDNA, cardiolipin, SSA and SSB. Seroreactivity to B. burgdorferi antigens by the ELISA system was detected in 40% of patients with SLE, 8% of patients with rheumatoid arthritis and 4% with seronegative arthritis. Among patients seropositive by ELISA, immunoblots were negative in all cases. However, eight of 14 patients with rheumatoid arthritis (57%) showed cross-reactivity to multiple borreli antigens. No significant correlations were found between Lyme seropositivity by ELISA and other autoantibodies except IgM rheumatoid factor (r = 0.61, P < 0.01) in patients with rheumatoid arthritis. IN CONCLUSION: a positive ELISA for Lyme disease was found in up to 40% of patients with established SLE and also in other rheumatic diseases. However, specific serum antibodies to Borrelia were not confirmed by the more specific immunoblot technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial

Inhibition of 3T3-L1 adipose differentiation by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced toxicity is particularly striking in adipose tissue, where it causes severe wasting. This phenomenon suggests that TCDD could have effects on adipocyte differentiation, now demonstrated using 3T3-L1 cells as a model system. When cells were treated with 10 nM TCDD before differentiation or during the first two days of induction in the presence of dexamethasone (dex) and isobutylmethylxanthine (IBMX), a reduction occurred in the number of fat cell colonies measured 7-10 days later by Oil Red O staining. Northern blotting showed an accompanying reduction in amounts of mRNA encoding several adipocyte markers. In contrast, when TCDD was added after differentiation, it had no effect on the maintenance of the adipose phenotype. Dose-response and structure-activity relationships were consistent with a process mediated by interaction of TCDD with the Ah receptor. The possibility that TCDD acts by inhibiting the signaling pathways activated by dex and IBMX was investigated. TCDD did not interfere with glucocorticoid-inducible transcription as judged by the unimpaired responsiveness of a transfected reporter construct. Treatment of cells with TCDD augmented the increase in protein kinase A (PKA) activity elicited by either IBMX or forskolin; therefore, if TCDD disrupts the cAMP signaling pathway, it must do so at a step after activation of PKA.

1-Methyl-3-isobutylxanthine

Advance directives for elderly people: worthwhile cause or wasted effort?

This article examines whether elderly individuals who had executed an advance directive for health care were more likely to have their wishes understood by their designated surrogates than elderly individuals who had not executed an advance directive. A sample of 153 elderly people was drawn from two nursing homes and two senior citizen housing complexes; 40 of the participants had executed an advance directive. Concordance was measured using six hypothetical health care scenarios and was evaluated by assessing the percentage of agreement and directionality of discordant responses. The mere completion of an advance directive did not guarantee a surrogate decision maker's awareness of the older person's wishes. Education, communication, and supportive intervention are also needed. As educators, facilitators, and enablers, social workers are well suited for this role.

Advance Directives

Boron neutron capture therapy: a mechanism for achieving a concomitant tumor boost in fast neutron radiotherapy.

PURPOSE: For many years neutron radiation has been used to treat malignant disease both as fast neutron radiotherapy and as thermal neutron induced boron neutron capture therapy (BNCT). To date, these two approaches have been used independently of one another due to the large difference in neutron energies each employs. In this paper we discuss the potential application of BNCT to enhance the therapeutic effectiveness of a fast neutron radiotherapy beam. METHODS AND MATERIALS: Measurements are presented for the thermal neutron component that is spontaneously developed as the University of Washington fast neutron radiotherapy beam penetrates a water phantom. The biological effect of this thermalized component on cells "tagged" with boron-10 (10B) is modeled mathematically and the expected change in cell survival calculated. The model is then extended to estimate the effect this enhanced cell killing would have for increased tumor control. RESULTS: The basic predictions of the model on changes in cell survival are verified with in vitro measurements using the V-79 cell line. An additional factor of 10-100 in tumor cell killing appears achievable with currently available 10B carriers using our present neutron beam. A Poisson model is then used to estimate the change in tumor control this enhanced cell killing would produce in various clinical situations and the effect is sufficiently large so as to be clinically relevant. It is also demonstrated that the magnitude of the thermalized component can be increased by a factor of 2-3 with relatively simple changes in the beam generating conditions. CONCLUSION: BNCT may provide a means of enhancing the therapeutic effectiveness of fast neutron radiotherapy in a wide variety of clinical situations and is an area of research that should be aggressively pursued.

Boron Neutron Capture Therapy

Serum lipid levels in growth hormone-deficient men.

To evaluate the impact of growth hormone deficiency (GHD) on lipid metabolism, serum lipid and apolipoprotein concentrations were measured in 64 GHD adult males (mean age, 27.1 +/- 4.7 years). Results were compared with those obtained from an age- and sex-matched control group. Total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein (apo) B levels were significantly higher in GHD patients (P < .001). In 14 patients (23%), total cholesterol concentration exceeded the 95th percentile for healthy adults. Total and LDL cholesterol were inversely related to plasma insulin-like growth factor-I (IGF-I). Apo B also tended to be negatively correlated with IGF-I; however, statistical significance was not reached (P = .054). High-density lipoprotein (HDL) cholesterol and plasma triglyceride concentrations were within normal limits, whereas apo A-1 and A-2 levels were only slightly different from normal. We conclude that GHD in adulthood is associated with mild hypercholesterolemia due to an increased LDL cholesterol level. An inverse relationship was established between LDL cholesterol concentration and GH secretory status.

Adolescent

Clinical paths for cardiac surgery patients: a multidisciplinary approach to quality improvement outcomes.

Implementation of clinical paths has resulted in a successful multidisciplinary approach for monitoring quality improvement outcomes in a select group of cardiovascular patients. This article defines clinical paths and explains their development, implementation, and evaluation. It also discusses how variances (which are defined as discrepancies between expected and actual events) were identified and how this information led to actions to improve patient outcomes. The roles of each health care professional are discussed in relation to clinical paths, and positive outcomes for the nurse, other health care professionals, and the institution are presented.

Clinical Protocols

Grease gun injuries to the orbit and adnexa.

The grease gun injury is an uncommon injury to the orbit. However, high-pressure injection of grease, oil, or paint is frequently reported in injuries of the hand and usually affects the fingers or palm, which require complicated surgical and medical care. Two cases of grease gun injury to the orbit are reported: one, a catastrophic injury, and the other resulting in satisfactory recovery after surgical debridement and adjuvant medical treatment. Presentation, investigation, and therapy are discussed.

Accidents, Occupational

Metabolic and environmental origins of volatile organic compounds in breath.

Although more than 200 volatile organic compounds (VOCs) have been identified in human alveolar breath, their origins are still mostly unknown. An attempt was made to determine whether the major VOCs in breath were derived from inside or outside the body--that is, were they products of metabolism or contaminants from the environment? The concentrations were measured of the 24 most abundant VOCs in the alveolar breath of 12 normal volunteers and also in the air they inspired. The polarity of the mean alveolar gradient (concentration in breath minus concentration in inspired air) was positive in 15 VOCs and negative in nine. The mean alveolar gradient varied from strongly positive (for example, 2,3,3-trimethylpentane), consistent with a metabolite manufactured in the body, to strongly negative (for example, isoprene), consistent with ingestion of an air pollutant which was then catabolised in vivo or excreted via an extra-pulmonary pathway.

Breath Tests

Ryanodine and dihydropyridine binding patterns and ryanodine receptor mRNA levels in myopathic hamster heart.

We have determined the densities of sarcolemmal voltage-dependent Ca2+ channels (VDCC) and Ca(2+)-induced Ca2+ release channels (CICR) of sarcoplasmic reticulum (SR) in the cardiomyopathic hamster heart using [3H]PN-200 and [3H]ryanodine, respectively. Partially purified cardiac membrane preparations from myopathic animals exhibit a twofold higher capacity to bind both [3H]PN-200 and [3H]ryanodine. Crude particulate membrane fractions from normal and cardiomyopathic animals reveal no significant difference in receptor densities for [3H]PN-200, whereas densities for [3H]ryanodine binding sites and mRNA levels are significantly (P < 0.05) diminished in cardiomyopathic animals. Inhibition of [3H]ryanodine binding by either Ca2+ or Mg2+ (in mM) as well as temperature dependence for receptor activation for [3H]ryanodine (Q10) is not significantly different, whereas membranes isolated from cardiomyopathic hearts are 1.4-fold and threefold more sensitive to activation by doxorubicin and Ca2+ (in microM), respectively. Vesicles isolated from myopathic hearts are more sensitive to inhibition of Ca2+ uptake by doxorubicin. The higher densities of binding sites for [3H]PN-200 and [3H]ryanodine observed in partially purified membrane fractions from cardiomyopathic hearts are more likely the result of altered patterns with which T-tubule and CICR channels fractionate in preparations from cardiomyopathic hamster heart rather than transcriptional upregulation and may be a consequence of the deficiency in a dystrophin-associated glycoprotein recently identified. Downregulation and functional changes in CICR channels may alter SR Ca2+ transport and contribute to the progression of cardiomyopathy in the hamster.

Animals

Phase II trial of docetaxel in patients with platinum-refractory advanced ovarian cancer.

PURPOSE: This phase II study was conducted to evaluate the efficacy and toxicity of docetaxel in the treatment of patients with platinum-refractory ovarian cancer. PATIENTS AND METHODS: Twenty-five patients with platinum-refractory advanced ovarian cancer were treated. Twenty of the patients had failed to respond to platinum-based front-line chemotherapy and five had failed to respond to platinum-based therapy repeated at relapse. One patient had received prior pelvic radiation therapy. Patients were required to have bidimensionally measurable disease. Docetaxel was administered at a dose of 100 mg/m2 intravenously (i.v.) over 1 hour every 21 days. Twenty patients received no corticosteroid premedication and five received premedication with corticosteroids and antihistamines. RESULTS: Eight of 23 assessable patients (35%) had a partial response (PR; 95% confidence interval, 16% to 57%). The median response duration was 5 months. Hospitalization for toxicity, predominantly neutropenic fever, occurred in 12 patients (48%) and 16% of courses. Anemia was common in the study population. Nonhematologic toxicities included alopecia, rash, fluid retention, diarrhea, peripheral neuropathy, and hypersensitivity reactions. CONCLUSION: Docetaxel demonstrates significant activity in patients with platinum-refractory advanced ovarian cancer. Routine premedication is recommended. Further investigations of this agent in ovarian cancer, including combinations with other active agents, appear indicated.

Adult

Network commercials promote legal drugs: outnumber anti-drug PSA's 45-to-1.

During the week of September 16 to 22, 1990, commercials promoting drugs and alcohol outnumbered the networks' news stories, documentaries, and PSA's about illegal drugs by a ratio of almost 39-to-1. If you consider the PSA's alone, the commercials promoting drugs and alcohol outnumbered them by a ratio of almost 45-to-1.

Adolescent

Enhancement of fast neutron beams with boron neutron capture therapy. A mechanism for achieving a selective, concomitant tumor boost.

Both fast neutron radiotherapy and boron neutron capture therapy (BNCT) have been utilized to treat malignant disease. Herein we discuss the potential of combining these treatments to enhance the effectiveness of fast neutron therapy through a concomitant BNCT boost. Using a fast neutron beam generated from a 50 MeV proton on beryllium reaction, we have determined that 0.1% of the beam per microgram of boron-10 per gram of tissue (microgram/g) can be deposited via BNCT. Our mathematical modeling predicts that BNCT enhancement of our beam will lead to an additional 1-2 logs of tumor cell kill for boron-10 concentrations of 30-50 micrograms/g. We have validated this via V-79 cell line in vitro measurements. A Poisson model estimation of how this additional cell kill will influence local tumor control, predicts that BNCT enhancement of fast neutron radiation will lead to a clinically significant improvement in outcome.

Animals