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Biomedical subjects

S F Jones

Publications and source records attributed to S F Jones.

At least 19 recordsLinked to original sources
PubMed1998

A phase I trial of vinorelbine in combination with mitoxantrone in patients with refractory solid tumors.

Vinorelbine (Navelbine) is a unique semi-synthetic vinca-alkaloid with a favorable safety profile that has demonstrated significant antitumor activity in patients with non-small cell lung cancer, advanced breast cancer, advanced ovarian cancer and Hodgkin's disease. The most common dose-limiting toxicity is neutropenia, while other reported toxicities are minimal. Mitoxantrone (Novantrone) is an anthracene derivative that has demonstrated antitumor activity in patients with breast cancer, ovarian cancer, acute leukemia, and lymphoma. Mitoxantrone also has a very favorable toxicity profile with significantly less nausea and vomiting, alopecia, and stomatitis as compared with anthracyclines. The dose-limiting toxicity for mitoxantrone is leukopenia. The study was designed to determine the safety and maximally tolerated dose of IV vinorelbine used in combination with a fixed dose of mitoxantrone for the treatment of patients with refractory solid tumors. Vinorelbine was administered on days 1 and 8 of the treatment regimen as a short IV infusion. The starting dose was 15 mg/m2. Mitoxantrone was administered as a 20-min infusion on day 1 only at a fixed dose of 10 mg/m2. Seventeen patients with solid malignancies were entered in the study. For personal reasons, one patient decided to discontinue the treatment after day 1 of cycle 1. Therefore, 16 patients were evaluable for toxicity. The main toxicity was myelosuppression which was dose-limiting and resulted in dose reductions and delays. The use of G-CSF had a minimal overall impact on this regimen. Stable disease was observed in three cases. In patients previously treated with chemotherapy, the maximally tolerated dose was defined as vinorelbine 20 mg/m2 on days 1 and 8 and mitoxantrone 10 mg/m2 on day 1 without growth factor support. These doses can be recommended for phase II study of the regimen as salvage treatment.

Adult↗
PubMed1997

Orofacial granulomatosis: a diagnostic problem for the unwary and a management dilemma. Case reports.

Orofacial granulomatosis is a condition that may be difficult to diagnose for those unfamiliar with the entity. This paper describes two cases and addresses the presentation, pathogenesis and treatment. The clinical recognition of this condition is important as is the subsequent investigation by an appropriate specialist. Management of patients needs to take into account the results of further investigations, the patient's expectations, and the severity of the condition.

Anti-Inflammatory Agents↗
PubMed1996

Vinorelbine: a new antineoplastic drug for the treatment of non-small-cell lung cancer.

OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, clinical activity, adverse effects, and dosage and administration guidelines for vinorelbine in the treatment of non-small-cell lung cancer (NSCLC). DATA SOURCES: A MEDLINE search (1989-1995) using the terms vinorelbine and Navelbine was conducted. Additional unpublished data were provided by Glaxo Wellcome Drug Information. STUDY SELECTION AND DATA EXTRACTION: The articles chosen for inclusion all appeared in peer-reviewed journals. Pertinent abstracts, as judged by the authors, were also included. DATA SYNTHESIS: Vinorelbine is a new semisynthetic vinca alkaloid approved by the Food and Drug Administration for the first-line treatment of patients with advanced NSCLC. The drug demonstrated a broad spectrum of antitumor activity in preclinical studies and produced dose-limiting neutropenia in Phase I trials. In Phase II studies, an overall response rate of approximately 30% was reported with single-agent vinorelbine. Furthermore, in large, multicenter, randomized Phase III trials, treatment with vinorelbine alone and in combination with cisplatin resulted in improved survival compared with controls. The drug was well tolerated, with granulocytopenia being the most commonly reported adverse effect. However, the incidence of fever and hospitalization associated with this granulocytopenia was exceptionally low. The recommended dose is 30 mg/m2 weekly administered by intravenous injection or infusion. CONCLUSIONS: As no specific chemotherapy regimen has previously been regarded as standard therapy for advanced NSCLC, vinorelbine is a promising new treatment for this patient population. It has been shown in several randomized, controlled trials to increase survival without compromising quality of life.

Antineoplastic Agents, Phytogenic↗
PubMed1994

NSAIDs.

Explore the source record for details and available documents.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1994

Evaluation of intravenous ketorolac administered by bolus or infusion for treatment of postoperative pain. A double-blind, placebo-controlled, multicenter study.

BACKGROUND: Ketorolac is a nonsteroidal analgesic that may provide postoperative analgesia without opioid-related side effects. This double-blind, randomized, multicenter study evaluated the analgesic efficacy and safety of intravenous ketorolac in 207 patients during the first 24 h after major surgery. METHODS: Subjects were assigned to receive one of three analgesic regimens: a ketorolac infusion, ketorolac boluses, or placebo. All subjects had access to intravenous morphine via patient-controlled analgesia (PCA). Evaluations included PCA morphine used, pain assessment (categorical pain intensity scores and visual analogue pain scores), pain relief (categorical pain relief scores), sedation, presence of adverse events, and overall rating of regimens by study observers and patients. RESULTS: Patients in the ketorolac infusion group (but not the ketorolac bolus group) used less morphine (average 33 mg) than did the placebo group (44 mg) (P = 0.009). Significant differences favoring both ketorolac groups were seen in the pain intensity and the categorical pain relief scores at various time points during the study. At the termination of the study, compared with the placebo group, categorical pain intensity scores were lower in the ketorolac bolus group; visual analogue pain scores were lower in both ketorolac groups; and pain relief scores were higher in the ketorolac bolus group. The incidence of vomiting was significantly greater in the placebo group (27%) than in the ketorolac infusion group (12%) or bolus group (9%) (P = 0.032 and P = 0.005, respectively). The incidence of postoperative fever was 10% in the ketorolac bolus group and 25% in the placebo group (P = 0.013). Study observers noted less nursing difficulty while caring for patients in the ketorolac infusion group (P = 0.015). Study observers and patients in both ketorolac groups reported statistically significant overall drug superiority compared with placebo. CONCLUSIONS: It is concluded that intravenous boluses or infusions of ketorolac in conjunction with PCA morphine provide effective, safe analgesia after major surgery and improve on the response to PCA morphine alone.

Adult↗
PubMed1988

Morphine and ibuprofen compared using the cold pressor test.

The analgesic efficacy of single doses of oral morphine sulphate solution (10 mg) and ibuprofen 600 mg was compared in 12 volunteers using a double-blind, double-dummy, placebo-controlled design on the cold pressor experimental pain model. Measurement of pain intensity was made before medication and then at 30, 60, 90, 120 and 180 min; blood samples were taken at these times for measurement of morphine and glucuronide metabolites by radioimmunoassay. Sessions were at least 5 days apart. Correlations were sought between analgesic effect and plasma concentrations of either morphine or morphine-6-glucuronide. Morphine produced significant reduction in both peak pain intensity and area under the pain intensity curve compared with placebo; the threshold time was significantly increased by morphine compared with placebo. Ibuprofen was statistically indistinguishable from placebo on all three measures of analgesia. Analgesic effect and plasma concentrations of morphine showed significant correlation (P = 0.053). The study confirmed reports of the opiate sensitivity of the cold pressor model, and the apparent insensitivity of the model to non-steroidal anti-inflammatory drugs.

Adult↗
PubMed1985

Analgesia following femoral neck surgery. Lateral cutaneous nerve block as an alternative to narcotics in the elderly.

In a prospective controlled randomised trial on patients undergoing operative repair of fractured neck of femur via a lateral incision, the postoperative analgesic requirements of one group of patients who received a lateral cutaneous nerve block were compared with a second group who received no block. The former group were found to need significantly less intramuscular pethidine in the first 24 hours, and 44% required no supplementary analgesia whatsoever during this period. The time to first dose of opioid in the remainder was greatly increased. No untoward sequelae associated with the nerve block were seen.

Aged↗
PubMed1973

Spontaneous quantal transmitter release: a statistical analysis and some implications.

1. Miniature end-plate potentials (m.e.p.p.s) were intra- and extracellularly recorded from neuromuscular junctions in rat phrenic nerve-diaphragm preparations in vitro.2. Statistical analysis of the intervals between m.e.p.p.s showed that when the mean number of events in time t was plotted as a function of the variance of the events in time t there was a significant deviation from the straight line relationship expected for a Poisson process. Computer simulation showed that this deviation is explicable if release was generated by the random phasing of the activity of a number of releasing sites.3. There was no indication that release of one quantum influences the probability of release of remaining quanta (drag, clustering). It is suggested that m.e.p.p.s whose amplitude is larger than the mode result from the release of the contents of vesicles whose volume is also supramodal.4. The effects of depolarization of nerve terminals upon the variance-mean curve suggest an increase in the activity of sites rather than an increase in their number.5. Statistical analysis indicated at least 200 +/- 100 (mean +/- 1 S.E.) releasing sites. This number is of the same order as the number of sites of vesicle aggregation and presynaptic membrane density seen in electron micrographs of nerve terminals of this preparation.

Animals↗
PubMed1971

The effect of temperature change upon transmitter release, facilitation and post-tetanic potentiation.

1. End-plate potentials (e.p.p.s) and miniature end-plate potentials (m.e.p.p.s) were intracellularly recorded from rat diaphragm phrenic nerve preparations in vitro at temperatures between 7 degrees and 40 degrees C.2. The quantal content of e.p.p.s and the frequency of m.e.p.p.s showed broadly similar relationships with temperature, with maxima about 20 degrees and above 39 degrees C.3. Analysis of the change in e.p.p. quantal content showed that the maximum about 20 degrees C was accompanied by a similar maximum of p, the probability of release of quanta. The maximum above 39 degrees C was associated with a rise in n, a presynaptic store of material needed for release.4. The rate at which transmitter could be mobilized was linear in an Arrhenius plot with an apparent activation energy of 25 kcal deg(-1).5. Facilitation and post-tetanic potentiation (PTP) were shown to be entirely attributable to changes in p.6. It is suggested that facilitation and PTP have a common basis and that the (temperature-dependent) rate of Ca removal from intracellular sites at which it exerts its action is as important a determinant of the magnitude of quantal release as is the amount of Ca combining with these sites.

Activation Analysis↗
PubMed1971

An investigation of experimental myasthenia gravis.

Guinea-pigs were immunized with antigen prepared from calf thymus and muscle, and from guinea-pig thymus, and rats were immunized with antigen prepared from rat thymus and rat muscle. There was an increased incidence of delayed hypersensitivity and circulating thymus antibodies in the immunized guinea-pigs and an increased incidence of thymitis in the immunized guinea-pigs and rats. However, when compared with control animals, there was no electrophysiological evidence of impairment of neuromuscular transmission in the immunized animals.

Action Potentials↗
PubMed1970

The effects of nerve stimulation and hemicholinium on synaptic vesicles at the mammalian euromuscular junction.

1. Electron micrographs of nerve terminals in rat phrenic nerve-diaphragm preparations have been studied. This has been done before and after prolonged nerve stimulation. The effectiveness of nerve stimulation has been monitored by intracellular micro-electrode recordings from the muscle cells.2. Characteristic changes in the form and distribution of the nerve terminal mitochondria were noted after nerve stimulation.3. Synaptic vesicle numbers in the region of nerve terminal less than 1800 A from the synaptic cleft were significantly greater in tissue taken 2 and 3 min after nerve stimulation, than in unstimulated preparations.4. The long and short diameters of the synaptic vesicle profiles less than 1800 A from the synaptic cleft were measured. Analysis of the distribution of the diameters indicated synaptic vesicles to be basically spherical structures. Estimates of synaptic vesicle volume were made from the measurements. Synaptic vesicle volume was significantly reduced in tissue taken 2 and 4 min following nerve stimulation.5. If hemicholinium, a compound which inhibits acetylcholine synthesis, was present during the period of nerve stimulation, much greater reductions in synaptic vesicle volume occurred. Synaptic vesicle numbers in the region of nerve terminal less than 1800 A from the synaptic cleft were also reduced, compared with unstimulated control preparations.6. These results are regarded as support for the hypothesis that the synaptic vesicles in nerve terminals at the mammalian neuromuscular junction represent stores of the transmitter substance, acetylcholine.

Acetylcholine↗
PubMed1970

Some effects of nerve stimulation andhemicholinium on quantal transmitter release at the mammalian neuromuscular junction.

1. Rat phrenic nerve-diaphragm preparations have been used to assess some effects of prolonged nerve stimulation on transmitter release.2. The amplitude of the end-plate potentials evoked by prolonged repetitive nerve stimulation fell gradually during stimulation. Most of this fall was due to a reduction in the number of transmitter quanta released by each nerve impulse; however there was also a small reduction in the muscle cell depolarization produced by each quantum of transmitter.3. Repetitive nerve stimulation also produced a small reduction in the amplitude of the miniature end-plate potentials. Recovery of amplitude occurred within about 7-8 min of ceasing stimulation.4. A much greater reduction in miniature end-plate potential amplitude accompanied prolonged nerve stimulation if hemicholinium was present in the bathing solution.5. Estimates of the ;readily available transmitter' (Elmqvist & Quastel, 1965b) were made at intervals following prolonged nerve stimulation. Readily available transmitter was reduced, and recovered over approximately 15 min.6. The relationship of these changes to the changes in nerve terminal synaptic vesicle numbers and volumes induced by similar prolonged nerve stimulation (Jones & Kwanbunbumpen, 1970) is discussed.

Animals↗