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Biomedical subjects

T Phillips

Publications and source records attributed to T Phillips.

At least 37 records · Page 2Linked to original sources
PubMed1996

A humanized system for pharmacologic control of gene expression.

Gene therapy was originally conceived as a medical intervention to replace or correct defective genes in patients with inherited disorders. However, it may have much broader potential as an alternative delivery platform for protein therapeutics, such as cytokines, hormones, antibodies and novel engineered proteins. One key technical barrier to the widespread implementation of this form of therapy is the need for precise control over the level of protein production. A suitable system for pharmacologic control of therapeutic gene expression would permit precise titration of gene product dosage, intermittent or pulsatile treatment, and ready termination of therapy by withdrawal of the activating drug. We set out to design such a system with the following properties: (1) low baseline expression and high induction ratio; (2) positive control by an orally bioavailable small-molecule drug; (3) reduced potential for immune recognition through the exclusive use of human proteins; and (4) modularity to allow the independent optimization of each component using the tools of protein engineering. We report here the properties of this system and demonstrate its use to control circulating levels of human growth hormone in mice implanted with engineered human cells.

Animals↗
PubMed1996

The cementless anatomic medullary locking femoral component: an independent clinical and radiographic assessment.

OBJECTIVE: To review the clinical performance of the anatomic medullary locking (AML) femoral stem in total hip arthroplasty. DESIGN: A clinical and radiographic review. SETTING: A tertiary lower limb joint replacement centre. PATIENTS: Two hundred and twenty-one patients with noninflammatory gonarthrosis. INTERVENTIONS: Two hundred and twenty-seven primary total hip arthroplasties with the noncemented AML component completed by two surgeons. MAIN OUTCOME MEASURES: Independent review by two experienced reviewers of the postoperative Harris hip score, radiographs of component fixation, size and degree of diaphyseal fill. RESULTS: Harris hip score was 84 (range from 43 to 98); component fixation showed bone ingrowth in 41%, stable fixation with fibrous ingrowth in 56% and unstable fixation in 3%; severe thigh pain in 4% of cases correlated with unstable fixation, and there was mild thigh pain in 20% of cases. CONCLUSION: The AML femoral stem performs well in replacement arthroplasty compared with other noncemented stems.

Adult↗
PubMed1995

Synthesis and characterization of hydroxylated polychlorinated biphenyls (PCBs) identified in human serum.

Hydroxylated polychlorinated biphenyls (PCBs) have been identified in wildlife and human samples. Most of these compounds are highly chlorinated (penta-hepatachloro) and contain a single meta- or para-hydroxyl group. Using the Cadogan coupling procedure, the following hydroxy-PCBs congeners were synthesized: 2,3,3',4',5-pentachloro-4-biphenylol, 2,3',4,4',5-pentachloro-3-biphenylol, 2',3,3',4',5-pentachloro-4-biphenylol, 2,2',3',4,4'-pentachloro-3-biphenylol, 2,2',3,3',4',5-pentachloro-4-biphenylol, 2,2',3',4,4',5-hexachloro-3-biphenylol, 2,2',3,4',5,5'-hexachloro-4-biphenylol, 2,2',3,3',4',5,5'-heptachloro-4-biphenylol, 2,2',3',4,4',5,5'-hepatachloro-3-biphenylol, 2,2',3,4',5,5',6-heptachloro-4-biphenylol. Many of these compounds have been detected as residues in human serum and current studies are investigating their activities as agonists and antagonists for several endocrine-mediated responses.

Gas Chromatography-Mass Spectrometry↗
PubMed1994

A study of the impact of leg ulcers on quality of life: financial, social, and psychologic implications.

BACKGROUND: Leg ulcers affect probably 2.5 million persons in the United States, and their prevalence is likely to rise as the population ages. They cause considerable disability, and the cost of treating these chronic wounds is enormous. OBJECTIVE: The purpose of this study was to assess the financial, social, and psychologic implications of leg ulcers. METHODS: Data were collected by standardized personal interviews with 73 patients with chronic leg ulcers. The interview covered several domains that were selected to determine the impact of a leg ulcer on overall quality of life. RESULTS: A significant number of patients had moderate to severe symptoms, principally pain, related to the leg ulcer. Eighty-one percent believed that their mobility was adversely affected by the ulcer; the dominant predictor of impaired mobility was swelling of the leg (p < 0.001). For younger, working patients, leg ulceration was correlated with time lost from work (p < 0.001), job loss (p < 0.01), and adverse effects on finances (p < 0.02). Fifty-eight percent of patients found caring for the ulcer burdensome. There was a strong correlation between time spent on ulcer care and feelings of anger and resentment. Sixty-eight percent of patients reported that the ulcer had a negative emotional impact on their lives, including feelings of fear, social isolation, anger, depression, and negative self-image. CONCLUSION: Leg ulcers pose a substantial threat to a variety of dimensions of a patient's quality of life.

Adult↗
PubMed1994

Posttranscriptional effector domains in the Rev proteins of feline immunodeficiency virus and equine infectious anemia virus.

By systematically dissecting the Rev proteins of feline immunodeficiency virus (FIV) and equine infectious anemia virus (EIAV), we have identified within each a short peptide that is functionally interchangeable with the effector domains found in Rev-like proteins from other retroviruses. The active sequences from FIV and EIAV differ in several respects from other known effectors and may represent a distinct class of effector domain.

Amino Acid Sequence↗
PubMed1993

CT characteristics of patients with brain metastases treated in RTOG study 79-16.

The search continues for a favorable subgroup of patients with brain metastases in whom testing of new modalities might show a benefit in overall survival. Complete pre- and post-treatment CT evaluation of the brain was performed in 779 of the 859 patients entered into RTOG protocol 7916, a phase III study of the role of misonidazole combined with radiation therapy in the treatment of brain metastases. Pretreatment scan findings of mass effect, midline shift, massive edema, central necrosis, location of sentinel lesion, and number of lesions were correlated with length of survival for all patients as well as for each treatment group. The only characteristics that showed a statistically significant difference in survival in the overall group were the presence of < or = 3 lesions and the presence of a midline shift. The actual benefit in overall survival, however, was found to be only 3 weeks. The volume of the largest lesion prior to treatment did not correlate well with survival, nor did location of lesions. The time to response, number of responders and absolute decrease in number of lesions were similar for the four treatment arms. Patients who responded to cranial treatment had a significantly prolonged survival over those who did not respond. No CT characteristic evaluated in this study showed value as a clinically relevant prognosticator for patients with brain metastases for the overall group. Patients who fulfilled three of the four favorable clinical characteristics previously described by Diener-West (age < or = 60, KPS > or = 70, primary lesion absent or controlled and brain as sole site of metastasis), were analyzed separately. Those with < or = three lesions had a statistically significantly prolonged survival over those with four or more lesions.

Brain Neoplasms↗
PubMed1993

Helium ions versus iodine 125 brachytherapy in the management of uveal melanoma. A prospective, randomized, dynamically balanced trial.

PURPOSE: Optimal radiation therapy for uveal melanoma is uncertain, and the relative efficacies of radioactive plaques and charged particles are unclear. METHODS: The authors prospectively studied helium-ion irradiation and iodine 125 (125I) brachytherapy in a randomized, dynamically balanced trial. Of the 184 patients who met the eligibility criteria, 86 were treated with helium ions and 98 with 125I brachytherapy. RESULTS: No patients with uveal melanoma had a history of systemic malignancy. Tumors were less than 15 mm in maximum diameter and less than 10 mm in thickness. A minimum tumor dose of 70 GyE was delivered to the tumor apex. There was a significantly higher local recurrence rate after 125I brachytherapy than after helium-ion irradiation. Enucleations occurred more frequently after brachytherapy (relative risk = 1.99; 95% confidence interval, 0.78-5.78). More anterior segment complications occurred after helium-ion irradiation. To date, there has been no measurable impact on survival. CONCLUSIONS: Most uveal melanomas can be managed with radiation with retention of the eye. There was better tumor control with helium-ion irradiation; however, there were more anterior segment complications.

Adult↗
PubMed1992

Detection of feline immunodeficiency virus (FIV) nucleic acids in FIV-seronegative cats.

A study was undertaken to determine the rate of viral transmission among naive specific-pathogen-free (SPF) cats living in close contact with feline immunodeficiency virus (FIV)-infected cats. Twenty SPF cats were housed in the same rooms with experimentally FIV-infected seropositive and virus culture-positive cats for 2 to 4 years and were monitored for the presence of FIV nucleic acids and antibodies. Only 1 of the 20 cats became seropositive and virus culture positive and developed signs of disease. Genomic DNA from bone marrow and peripheral blood mononuclear cells (PBMC) of 10 of 19 healthy-appearing seronegative cats became positive for FIV DNA by the polymerase chain reaction. Twenty-eight SPF cats housed as groups in separate quarters and never exposed to FIV-infected cats were uniformly negative for FIV DNA. FIV RNA transcripts were detected in concanavalin A-stimulated PBMC cultures from 4 of 10 FIV DNA-positive, seronegative cats by in situ hybridization. PBMC from three of four naive SPF cats acquired FIV nucleic acids after the cats were transfused with blood and bone marrow from FIV genome-positive, seronegative donors. Three of five FIV-seronegative cats housed for years with naturally FIV-infected cats in a private household were also found to harbor FIV DNA, indicating that the same phenomenon occurred in the field. These findings demonstrate that cats living in close contact with FIV-infected seropositive cats can acquire FIV nucleic acids without developing detectable levels of serum antibodies or disease.

Animals↗
PubMed1992

Voices from family medicine: Theodore Phillips. Interview by William B. Ventres and John J. Frey.

Ted Phillips has had a remarkable career in medicine. He practiced in a rural Alaskan town, helped build the University of Washington's Department of Family Medicine as its founding chair, labored as an associate and acting dean at the university, and, more recently, returned to clinical practice part time on a small island in Washington state and travels to the University of Washington to direct the course on introduction to clinical medicine. Dr. Phillips was president of the Society of Teachers of Family Medicine in 1978-1979 and received the Society's Certificate of Excellence in 1981. He currently serves as the only community-based physician on the National Advisory Council of the Agency for Health Care Policy and Research. This transcript is an abridged version of interviews conducted in April and June 1992.

Family Practice↗
PubMed1991

Clinical trials with etanidazole (SR-2508) by the Radiation Therapy Oncology Group (RTOG).

Following the completion of a phase I study of etanidazole (SR 2508), a new hypoxic cell sensitizer, the RTOG, began a phase II/III trial. The objectives of the study were to determine the toxicity and efficacy of SR 2508, combined with conventional radiotherapy for the management of unresectable stage III and IV head and neck squamous carcinomas. During the first step (or the Phase II portion) of the study, 33 patients received radiotherapy plus SR 2508 (RT + SR 2508). The incidence of drug toxicities was modest; including 24% grade I peripheral neuropathy (PN), 6% grade II PN, 27% grade I or II nausea and vomiting, 9% allergy and 15% reversible neutropenia. Because observed toxicities were deemed acceptable, the second step (or phase III portion) was then activated. Patients were randomized to receive either RT or RT + SR 2508. As of November 20, 1989, a total of 242 patients have been entered onto the Phase III portion of the study. One hundred twenty-two patients were randomized to the RT + SR 2508 arm and 120 patients were randomized to the RT alone arm. The analyses presented in this report are based on data available. The incidence of drug toxicities has been low, with 18% grade I or II PN, 26% nausea and vomiting (including one grade III), 14% allergy (including one grade III) and 13% reversible neutropenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Squamous Cell↗
PubMed1991

Rapidly alternating radiotherapy and high dose cisplatin chemotherapy in stage IIIB non-small cell lung cancer: results of a phase I/II study.

Alternating radiotherapy and chemotherapy increases tumor cure rates in some animal models with reduced normal tissue damage compared to sequential use of these modalities. To test this concept in non-small cell lung cancer, 23 patients with predominantly Stage IIIB disease were treated on a Northern California Oncology Group pilot study of alternating radiotherapy and high dose cisplatin. Radiotherapy consisted of 6000 cGy delivered in three separate 10-day courses of 200 cGy/fraction/day during weeks 1 and 2, 5 and 6, and 9 and 10. High dose cisplatin, 100 mg/m2 in 3% saline, was administered on weeks 3 and 4, 7 and 8, 11 and 12, and 15 and 16. The response rate in 22 eligible patients is 73% (16/22) with four complete responses and 12 partial responses. Feasibility of this approach is demonstrated by 20/22 patients completing radiotherapy and a median of 2.5 courses of chemotherapy administered. Median survival time is 14.2 months (range 2-40+ months). One- and 2-year survival rates are 64% (14/22) and 41% (9/22), respectively. Hematologic, renal, and radiation-related toxicities were significant but manageable. We conclude that rapid alternation of radiotherapy and a high dose intensity cisplatin regimen is feasible in Stage IIIB non-small cell lung cancer, with a high response rate and acceptable toxicity. The long-term impact on local control and survival remains unclear, although preliminary survival data are encouraging in this poor prognosis population. Further studies of this concept are warranted.

Adenocarcinoma↗
PubMed1991

Role of diagnostic techniques in the initial evaluation of stab wounds to the anterior abdomen, back, and flank.

Despite the widespread availability of firearms, stab wounds to the abdomen, back, and flank continue to account for a significant number of injuries. The proper sequencing of diagnostic modalities in this patient group is constantly undergoing change. We report our experience with these injuries and present a new algorithm for the use of currently available diagnostic procedures. In 1987, 162 patients were seen, 103 with anterior abdominal wounds and 59 with back and flank wounds. Patients with shock, peritonitis, and evisceration were resuscitated and explored. The remainder of the cohort underwent tap and lavage, and patients with a negative study were observed. Patients with back and flank wounds underwent contrast enhanced computerized tomographic enemas (CECTE). Seventeen patients underwent immediate exploration and 108 of the 162 patients were spared exploration. Fifty-four patients were explored with six negative laparotomies. Of the 126 taps and lavages, the false positive rate was zero, and only one patient had a false negative study. Of the 47 CECTE studies, only three were interpreted as an indication for angiography which proved negative, and all patients were safely observed. The overall mortality was 4.3%, including three patients without vital signs on admission and four who expired intraoperatively due to irreversible shock. We concluded that this algorithm can be safely applied to patients with these injuries with a high degree of specificity and sensitivity.

Abdominal Injuries↗
PubMed1990

Increased expression of a putative adenoma-associated antigen in pre-colonoscopic effluent of patients with colorectal cancer.

A monoclonal antibody Adnab-9, was raised against antigens derived from benign polyps of the colon. Adnab-9 was tested against pre-colonoscopic effluent material obtained from groups of patients with a macroscopically normal colonscopic examination, histologically confirmed adenomatous polyps and patients with colorectal cancer (CRC). The resultant binding levels displayed little overlap between the CRC group and the normal, and the difference was statistically significant. Since this putative early neoplasia associated antigen is essentially not expressed in CRC extracts, it may originate from a region of the colon predisposed to neoplasia, increasing in expression as the tendency to malignancy progresses, useful in the diagnosis of early stage malignancy.

Adenoma↗