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P Anderson

Publications and source records attributed to P Anderson.

540 records · Page 30Linked to original sources
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Preliminary phase II clinical and pharmacokinetic study of 9-cis retinoic acid in advanced cervical cancer. New York Gynecologic Oncology Group.

PURPOSE: 9-cis retinoic acid (ALRT 1057; 9cRA) is a promising new retinoid that binds to all known retinoic acid receptors (RAR and RXR), potentially providing it with a broader spectrum of biologic activity than either 13-cis retinoic acid or all-trans retinoic acid. It has been shown to be at least as active as all-trans retinoic acid as a differentiation-inducing and antiproliferative agent in both in vivo and in vitro tumor model systems. METHODS: The New York Gynecologic Oncology Group undertook a prospective, multi-institutional phase II clinical and pharmacokinetic trial of 9cRA in patients with advanced or recurrent squamous cell or adenosquamous cell carcinoma of the uterine cervix. Patients received daily oral doses of 140 mg/m2 of 9cRA. 9cRA and its metabolites were determined by reversed-phase HPLC in plasma samples drawn at 0.5 to 8 hours. RESULTS: Sixteen patients with advanced or recurrent carcinoma of the cervix were enrolled. Therapy was well tolerated with no unexpected toxicities. There were no complete or partial responses observed, indicating that a response rate of 20% or greater to this agent could be ruled out with 95% confidence. Pharmacokinetic parameters for 9cRA on day 1 were in agreement with previous studies. The area under the plasma versus time curves for 9cRA declined by 69% between days 1 and 8 with daily 9cRA dosing and remained at this low level in those patients evaluated on day 28. 4-oxo-9-cis retinoic acid (4-oxo-9cRA) was identified as a major plasma metabolite of 9cRA. Plasma levels of 4-oxo-9-cRA were initially 71% of those of 9cRA, but in contrast to 9cRA, there was no decline in plasma levels on days 8 and 28. The ratio of the area under the curve for the 4-oxo metabolite relative to that of the parent compound increased from less than 1 on day 1 to approximately 2.4 on days 8 and 28. Thus, despite early induction of its own metabolism, levels of total retinoid metabolites persisted at pharmacologic levels at day 28. CONCLUSIONS: 9cRA with this dose and schedule was inactive in women with advanced carcinoma of the cervix. Despite a decline in plasma levels of 9cRA over time, levels of the 4-oxo metabolite tended to persist. While the 4-oxo metabolite is less potent than the parent compound, these data nevertheless suggest that the lack of clinical activity in this patient population may not be attributable exclusively to suboptimal pharmacokinetic parameters.

Adult↗
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Bonus of contention.

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Attitude of Health Personnel↗
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A home for life.

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Aged↗
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Enough is enough.

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Aged↗
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Taking note.

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Attitude of Health Personnel↗
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Sitting pretty.

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Health Services Accessibility↗
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The temporal relationship of psychosocial stress to cellular immunity and herpes labialis recurrences.

This study used a prospective single-subject study design and time series analysis for repeated measures data to investigate the hypothesis that variations in psychosocial stress are associated with changes in cellular immunity in a study subject with recurrent herpes labialis. A study subject who was antibody positive for HSV-1 but reported no clinical manifestations of disease served as a control. Psychosocial stress, as measured by a questionnaire; cellular immunity, as measured by the monoclonal antibodies CD4 (OKT4), which defines the helper/inducer subset of T lymphocytes; and CD8 (OKT8), which defines the suppressor/cytotoxic subset, were measured weekly over the 32-week study period. Analysis of data using bivariate time series (ARIMA) demonstrated significant inverse correlations between stress level scores and percent CD4 helper/inducer T lymphocytes in both subjects. In the study subject with recurrent herpes simplex labialis, a Mann-Whitney U statistic determined that the percent of CD4 in the early stages of a recurrence were significantly lower than the percent of CD4 at other times when blood samples were drawn. The data presented are repeated measures on two individuals with positive antibodies to the herpes simplex virus, one with recurrent herpes and one without a history of recurrent herpes. Relevance for stress research is discussed.

Adult↗
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Diaphyseal primary subacute osteomyelitis in children.

Six patients with subacute diaphyseal osteomyelitis of 200 with acute osteomyelitis who were seen and treated at the Red Cross Children's Hospital in a 3-year period (1985-1987) are reported. All six patients had a history of a minimum of 2 weeks' duration and the radiographic picture of a linear periosteal reaction, which was either single or laminated. This radiographic picture was indistinguishable from round cell tumors of bone. The final diagnosis was established by a histology consistent with a subacute osteomyelitis. In two patients, a positive culture of Staphylococcus aureus was obtained. All of the patients healed after treatment with cloxacillin. Radiographic resolution was noted in all patients within 6 months of treatment.

Biopsy↗
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Nursing the nomads.

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Community Health Centers↗