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R J Locke

Publications and source records attributed to R J Locke.

6 recordsLinked to original sources
PubMed2001

Natural vaginal progesterone is associated with minimal psychological side effects: a preliminary study.

The objective of this study was to evaluate the psychological side effects of a transvaginal natural progesterone gel in hormone replacement therapy (HRT). This 3-month preliminary study was part of a multicenter study previously performed in our center. We enrolled 49 women (ages 18-45 years) with hypothalamic amenorrhea (HA) (n = 40) and premature ovarian failure (POF) (n = 9). Estrogenized patients applied vaginal progesterone gel (4% or 8%) every other day for six doses per month. The Hopkins Symptom Checklist (HSCL), a psychometric profile test, was administered at baseline, day 13 of cycle 2, day 24 of cycle 2, and day 24 of cycle 3. Application of the progesterone gel caused no significant change in HSCL total scores or individual symptom scores for somatization, obsession-compulsion, interpersonal sensitivity, depression, and anxiety. Natural vaginal progesterone gel can be an effective alternative to oral progesterone for women on HRT.

Administration, Intravaginal↗
PubMed1999

Combretastatin A-4 phosphate as a tumor vascular-targeting agent: early effects in tumors and normal tissues.

The potential for tumor vascular-targeting by using the tubulin destabilizing agent disodium combretastatin A-4 3-0-phosphate (CA-4-P) was assessed in a rat system. This approach aims to shut down the established tumor vasculature, leading to the development of extensive tumor cell necrosis. The early vascular effects of CA-4-P were assessed in the s.c. implanted P22 carcinosarcoma and in a range of normal tissues. Blood flow was measured by the uptake of radiolabeled iodoantipyrine, and quantitative autoradiography was used to measure spatial heterogeneity of blood flow in tumor sections. CA-4-P (100 mg/kg i.p.) caused a significant increase in mean arterial blood pressure at 1 and 6 h after treatment and a very large decrease in tumor blood flow, which-by 6 h-was reduced approximately 100-fold. The spleen was the most affected normal tissue with a 7-fold reduction in blood flow at 6 h. Calculations of vascular resistance revealed some vascular changes in the heart and kidney for which there were no significant changes in blood flow. Quantitative autoradiography showed that CA-4-P increased the spatial heterogeneity in tumor blood flow. The drug affected peripheral tumor regions less than central regions. Administration of CA-4-P (30 mg/kg) in the presence of the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester, potentiated the effect of CA-4-P in tumor tissue. The combination increased tumor vascular resistance 300-fold compared with less than 7-fold for any of the normal tissues. This shows that tissue production of nitric oxide protects against the damaging vascular effects of CA-4-P. Significant changes in tumor vascular resistance could also be obtained in isolated tumor perfusions using a cell-free perfusate, although the changes were much less than those observed in vivo. This shows that the action of CA-4-P includes mechanisms other than those involving red cell viscosity, intravascular coagulation, and neutrophil adhesion. The uptake of CA-4-P and combretastatin A-4 (CA-4) was more efficient in tumor than in skeletal muscle tissue and dephosphorylation of CA-4-P to CA-4 was faster in the former. These results are promising for the use of CA-4-P as a tumor vascular-targeting agent.

Animals↗
PubMed1997

A charged-particle microbeam: I. Development of an experimental system for targeting cells individually with counted particles.

Charged-particle microbeams provide a unique opportunity to control precisely, the dose to individual cells and the localization of dose within the cell. The Gray Laboratory is now routinely operating a charged-particle microbeam capable of delivering targeted and counted particles to individual cells, at a dose-rate sufficient to permit a number of single-cell assays of radiation damage to be implemented. By this means, it is possible to study a number of important radiobiological processes in ways that cannot be achieved using conventional methods. This report describes the rationale, development and current capabilities of the Gray Laboratory microbeam.

DNA↗
PubMed1993

Treatment of foxglove extract poisoning with digoxin-specific Fab fragments.

A 22-year-old man presented to our emergency department after an intentional overdose of a homemade foxglove extract. Clinical symptoms with symptomatic bradyarrhythmia and ECG changes were consistent with cardiac glycoside poisoning. Treatment with digoxin-specific Fab fragments resulted in transient clinical and ECG improvement. Serum immunoassay demonstrated a digitoxin-like glycoside. The serum levels showed no evidence of altered elimination or distribution with Fab therapy despite temporary improvements in the clinical course. The use of Fab did not result in a shortened clinical course in this episode of foxglove poisoning, as one would expect in the setting of commercial glycoside product poisoning.

Adult↗
PubMedDate not supplied

Effects of combretastatin A4 phosphate on endothelial cell morphology in vitro and relationship to tumour vascular targeting activity in vivo.

BACKGROUND: Combretastatin A4 Phosphate (CA4P) is a tubulin binding agent which causes rapid tumour vascular shutdown. It has anti-proliferative and apoptotic effects on dividing endothelial cells after prolonged exposure, but these effects occur on a much longer time scale than the reduction in tumour blood flow. This study compared the time course of CA4P effects on endothelial cell shape and reduction in red cell velocity. METHODS: Endothelial cell area and form factor (1-4 pi x area x perimeter-2) were measured for proliferating and confluent HUVECs after CA4P treatment. Recovery of shape after CA4P and colchicine was compared. Window chamber studies of tumours were used to measure red cell velocity. Results 70% reduction in red cell velocity and 44% reduction in HUVEC form factor occurred by 10 minutes. Proliferating HUVECs underwent greater cell shape change after CA4P, which occurred at lower doses than for confluent cells. Cell shape recovered 24 hours after 30 minutes exposure to CA4P, but not after colchicine. CONCLUSIONS: The similar time course of cell shape change and red cell velocity reduction suggests endothelial cell shape change may be involved early in the in vivo events leading to vascular shutdown. Differences in the recovery from the shape changes induced by CA4P and colchicine could underlie the different toxicity profiles of these drugs.

Animals↗