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P J Flynn

Publications and source records attributed to P J Flynn.

At least 19 recordsLinked to original sources
PubMed1999

Activation of transcription by metabolic intermediates of the pyrimidine biosynthetic pathway.

Saccharomyces cerevisiae responds to pyrimidine starvation by increasing the expression of four URA genes, encoding the enzymes of de novo pyrimidine biosynthesis, three- to eightfold. The increase in gene expression is dependent on a transcriptional activator protein, Ppr1p. Here, we investigate the mechanism by which the transcriptional activity of Ppr1p responds to the level of pyrimidine biosynthetic intermediates. We find that purified Ppr1p is unable to promote activation of transcription in an in vitro system. Transcriptional activation by Ppr1p can be observed, however, if either dihydroorotic acid (DHO) or orotic acid (OA) is included in the transcription reactions. The transcriptional activation function and the DHO/OA-responsive element of Ppr1p localize to the carboxyl-terminal 134 amino acids of the protein. Thus, Ppr1p directly senses the level of early pyrimidine biosynthetic intermediates within the cell and activates the expression of genes encoding proteins required later in the pathway. These results are discussed in terms of (i) regulation of the pyrimidine biosynthetic pathway and (ii) a novel mechanism of regulating gene expression.

Animals↗
PubMed1998

Progress in reducing anticipatory nausea and vomiting: a study of community practice.

Chemotherapy-related nausea and vomiting (NV) in 300 consecutive patients treated in community practices prior to the availability of 5-HT3 antiemetics (9/87 to 1/91) were compared with NV in a second sample of 300 patients treated after their commercial introduction (9/93 to 2/95). Eighty-six percent of the later patients received 5-HT3 antiemetics, and significantly fewer (43.3%) reported one or more episodes of posttreatment vomiting during their first four cycles of chemotherapy compared with those in the previous sample (55.0%: P < .01). Identical numbers of both groups (79.3%) reported at least one episode of posttreatment nausea. A significant increase in the average duration of both posttreatment nausea (from 28.1 h to 37.2 h; P = 0.001) and posttreatment vomiting (from 10.9 h-16.5 h, P = .02) was found; no significant differences were seen in the reported severity of either symptom. The proportion of patients experiencing at least one episode of anticipatory nausea (31.0% vs 32.0%) or anticipatory vomiting (7.7% vs 6.3%) did not differ significantly (P > 0.5) between groups, nor were there significant differences in the duration or severity of anticipatory symptoms (P > 0.4 for all comparisons). The reduction in the frequency of posttreatment vomiting supports research findings of efficacy. Findings of an increase in duration of posttreatment nausea and emesis and no change in the frequency of posttreatment nausea or in anticipatory symptoms show a continuing need for progress in control of posttreatment emesis and emphasize the need for further research on the control of chemotherapy-induced nausea.

Adolescent↗
PubMed1997

Comparison of sevoflurane and halothane for outpatient dental anaesthesia in children.

In a prospective, randomized, double-blind clinical study, we have studied 100 children, aged 2-12 yr, to compare halothane and sevoflurane in outpatient dental anaesthesia. All patients were unpremedicated and received inhalation induction using nitrous oxide in oxygen supplemented with either halothane (maximum inspired concentration 5%) or sevoflurane (maximum inspired concentration 8%). Time to loss of the eyelash reflex was more rapid using sevoflurane although time to adequate anaesthesia (to allow insertion of a mouth prop) was slower in the sevoflurane group. The incidence of cardiac arrhythmia was higher during halothane (62%) than during sevoflurane anaesthesia (28%) (P < 0.005) and the arrhythmias were more often ventricular in origin. The two agents were comparable in terms of ease of use and quality of anaesthesia, and times to eye opening and satisfying discharge criteria were similar. We conclude that sevoflurane has qualities that have made halothane the most used inhalation agent for children, and that it is superior to halothane in dental outpatients where cardiac arrhythmias are a particular problem.

Ambulatory Surgical Procedures↗
PubMed1996

Post-operative pain relief in children following extraction of carious deciduous teeth under general anaesthesia: a comparison of nalbuphine and diclofenac.

In a randomized double-blind study 60 children, undergoing the extraction of carious deciduous teeth under day-case general anaesthesia, were assigned to receive either intravenous nalbuphine hydrochloride 0.3 mg kg-1 (n = 21), one or more diclofenac suppositories 12.5 mg to a dose of 1-2 mg kg-1 (n = 19), or no analgesia (n = 20). The duration of anaesthesia was longer in the diclofenac group (9.6 min, SD 3.5) compared with control (7.2 min, SD 2.6) and nalbuphine (6.9 min, SD 3.0) groups respectively (P < 0.05). There were no statistically significant differences in post-operative pain scores during the 45 min post-operative period studied between the three groups using an objective pain score. We conclude that using this methodology we were unable to demonstrate any statistically significant differences between the analgesic effects of either intravenous (i.v.) nalbuphine or diclofenac suppositories compared with control.

Acetaminophen↗
PubMed1996

Phase II trial of prolonged continuous infusion of 5-fluorouracil and interferon-alpha in patients with advanced pancreatic cancer. Eastern Cooperative Oncology Group Protocol 3292.

Evidence suggests that interferon-alpha (IFN-alpha) augments the antineoplastic activity of 5-fluorouracil (5-FU) in human adenocarcinoma cell lines in vitro and may enhance the efficacy of 5-FU in patients with advanced colorectal carcinoma. In addition, 5-FU may be more effective when given as a prolonged, continuous i.v. infusion (PCI). The Eastern Cooperative Oncology Group performed a Phase II trial of PCI 5-FU plus IFN-alpha in patients with advanced pancreatic carcinoma. Twenty-six patients with advanced, surgically incurable adenocarcinoma of the pancreas received PCI 5-FU (250 mg/m2 daily for 28 days) in combination with IFN-alpha (5 x 10(6) IU/m2 s.c. thrice weekly). Treatment cycles were repeated 14 days or longer after completion of the previous cycle. Treatment was interrupted prior to day 28 if intolerable toxicity developed, and the dose of 5-FU was reduced in subsequent cycles. Partial response occurred in two of 24 evaluable patients (8%; 95% confidence interval, 0-19%). The majority of the study group (88%) had liver metastases. Patients whose serum lactate dehydrogenase (LDH) was more than twofold elevated developed 5-FU-related toxicity significantly sooner than patients with smaller elevations in serum LDH (9 vs. 22 days; p = 0.003). A similar trend was observed for patients with a more than twofold elevation in serum glutamic-oxaloacetic transaminase (SGOT; 9 vs. 15 days; p = 0.07). In conclusion, PCI 5-FU plus IFN-alpha has minimal activity in patients with advanced pancreatic carcinoma, and elevated serum LDH and/or SGOT may be useful for predicting greater toxicity from 5-FU-based therapy in patients with liver metastases.

Adenocarcinoma↗
PubMed1996

A survey of close contact regimes between patients undergoing diagnostic radioisotope procedures and children.

When following diagnostic radioisotope procedures, UK legislation requires that we advise patients to avoid close contact with children [1, 2]. How does this advice affect the average nuclear medicine patient? Over a 4 month period, 90 patients in contact with children were asked about their home circumstances, how they coped with avoidance of close contact and the problems caused. On average, the patients were in contact with two children with a mean age of 7 years. Thirty-nine per cent of patients spent < 5 h per day and 30% between 5 and 10 h per day in close contact. However, 13% spent 20-24 h in close contact with children. For most patients (55%), it is easy to avoid close contact, but 25% found it difficult or very difficult. The average in-patient received one visit a day from children of 0.5-1 h duration and 65% of children sat on the patient's bed. Restriction of visits was a problem for 14% of patients. Initially, over one-third of the out-patients felt a medium level of anxiety or higher regarding close contact with children. Given more detailed written information and the opportunity to discuss any queries with a member of staff (70% wished to do so), the proportion fell to less than one-tenth. We found it important to question patients carefully, because home circumstances and levels of close contact cannot be deduced from the age of the child or the relationship between the child and the patient.

Adolescent↗
PubMed1996

Phase insensitive homomorphic image processing for speckle reduction.

Speckle appears in all conventional ultrasound images and is caused by the use of a phase-sensitive transducer. Speckle is an undesirable property as it can mask small but perhaps diagnostically significant image features. In this paper a homomorphic, hybrid nonlinear processing method, based on cancellation of scattering interference, is developed and examined. Experiments with synthetic and real ultrasound imagery show that the proposed method improves the contrast-to-noise ratio in both lesion and cyst areas and preserves edge clarity.

Computer Simulation↗
PubMed1995

Intubating conditions following 1R CIS, 1'R CIS atracurium (51W89). A comparison with atracurium.

51W89 besylate, a new intermediate acting non-depolarising muscle relaxant, consisting of a single stereo-isomer of the commercial preparation of atracurium has been assessed in respect of intubating conditions during nitrous oxide-propofol-isoflurane anaesthesia. Intubating conditions at 2 min were acceptable in 67% of patients following a dose of 0.1 mg.kg-1 and in 90% of patients following a dose of 0.15 mg.kg-1. Intubating conditions at 1.5 min were acceptable in 76% of patients following a dose of 0.2 mg.kg-1. In comparison, intubating conditions at 2 min were acceptable in 95% of patients following 0.5 mg.kg-1 of atracurium. The intubating conditions at 2 min following a dose of 0.1 mg.kg-1 51W89 besylate were significantly worse than the other three groups (p < 0.05); however, there was no significant differences between the scores in the other three groups. There was no clinical evidence of histamine release in the groups receiving 51W89 besylate compared to two out of the 19 patients who had cutaneous flushing following the administration of atracurium. Our results suggest that 51W89 besylate provides acceptable intubating conditions at 2 min following a dose of 0.15 mg.kg-1 and may prove to be an acceptable alternative to atracurium if studies in progress confirm its greater cardiovascular stability and reduced propensity to release histamine than its parent compound.

Adolescent↗
PubMed1995

Evaluation of neuromuscular effects and antagonism of rocuronium bromide: a preliminary report.

Twenty ASA I-II patients received either 2 or 3 x ED95 doses of rocuronium bromide during nitrous oxide, oxygen, propofol, fentanyl-based anaesthesia. The mean times to maximum block were 98 s and 74 s and the mean duration of clinical relaxation (recovery to 25% T1) was 35 min and 46 min following 620 micrograms kg-1 and 930 micrograms kg-1, respectively. Neuromuscular blockade was antagonized with either neostigmine or edrophonium from a twitch height of 25%. Although there was no significant difference between the recovery times neostigmine appeared to give more consistent antagonism of rocuronium-induced blockade.

Adolescent↗
PubMed1993

National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention Trial.

The Breast Cancer Prevention Trial is the largest breast cancer prevention study ever undertaken. Administered by the National Surgical Adjuvant Breast and Bowel Project, it is the first trial seeking to demonstrate whether a drug, tamoxifen, can prevent breast cancer in high-risk women. The objectives of this trial are to determine whether tamoxifen is effective in 1) reducing the incidence of invasive breast cancer, 2) reducing breast cancer mortality, 3) reducing deaths from cardiovascular disease, and 4) reducing bone fractures. In addition, the study will evaluate side effects, toxicity, and the quality of life of all study participants.

Adult↗
PubMed1992

Phase II trial of PALA in combination with 5-fluorouracil in advanced pancreatic cancer.

Phosphonacetyl-L-aspartate (PALA), in inhibitor of aspartate transcarbamylase that depletes uridine nucleotide pools, selectively potentiates the antitumor activity of 5-fluorouracil (5-FU) in preclinical models. Due to the promising results we obtained using PALA/5-FU in colorectal cancer, we performed a phase II trial in patients presenting with advanced pancreatic cancer. PALA was given intravenously at 250 mg/m2 on day 1, followed 24 h later by 2,600 mg/m2 5-FU given by 24-h infusion. Treatments were repeated weekly. A total of 41 patients who had not previously undergone chemotherapy were entered in the trial; of these, 35 were evaluable for response. Toxicity was generally mild to moderate; neurotoxicity (13/35) and diarrhea (8/35) predominated. Among the 35 patients, 1 achieved a complete response and 4, a partial remission, for an overall response rate of 14%. The median survival was 5.1 months. Pretreatment with PALA alone was not sufficient to enhance the activity of 5-FU in pancreatic cancer.

Adenocarcinoma↗
PubMed1991

Use of continuous positive airway pressure in paediatric dental extraction under general anaesthesia.

In a controlled prospective study, we studied 150 grade ASA I children undergoing outpatient dental extraction under inhalation anaesthesia with a T-piece system allocated to three equal groups: a control group (0 cm H2O CPAP), and two study groups receiving 2.5 or 5 cm H2O of CPAP via a nasal mask. We found that the incidence and severity of oxygen desaturation were reduced significantly in the 5-cm H2O CPAP group.

Adolescent↗
PubMed1991

Neuromuscular and clinical effects of mivacurium chloride in healthy adult patients during nitrous oxide-enflurane anaesthesia.

We have studied the effects of mivacurium after induction of anaesthesia with alfentanil-propofol in healthy adult oral surgical patients. Anaesthesia was maintained with nitrous oxide and 0.75% (end-tidal) enflurane in oxygen after nasotracheal intubation. Recordings were made of the rectified compound adductor pollicis electromyogram in response to train-of-four (TOF) ulnar nerve stimulation. First and fourth TOF responses were defined as T1 and T4, with T1 suppression referenced to pre-mivacurium T1 height (Tc). Onset times (mean (SEM] to 90% T1 suppression were 2.5 (0.2), 2.1 (0.3) and 1.6 (0.1) min, respectively, after mivacurium 0.15 mg kg-1 (n = 18) and 0.2 mg kg-1 (n = 18) as 5-s boluses and 0.2 mg kg-1 over 30 s (n = 9). Intubating conditions 2 min after 0.15 mg kg-1 were good to excellent and not improved by a further 30-s delay or by use of a 0.2-mg kg-1 dose. Recovery to T1/Tc of 5% occurred on average in 12-13 min irrespective of dose. Thereafter, mivacurium infusions commenced at 8-10 micrograms kg-1 min-1 were adjusted at intervals of at least 3 min to achieve T1/Tc in the range 1-10%. Mean duration of infusion was 58 (3.4) min and mean infusion rate after a 15-min stabilization period was 6.6 (range 2.3-12.9) micrograms kg-1 min-1. On cessation of infusions, spontaneous recovery from T1/Tc 8% (1.0%) to T4:T1 = 0.7 took 17 (1.2) min. Neostigmine 0.04 mg kg-1 or edrophonium 0.75 mg kg-1 evoked recovery from T1/Tc 9% (SEM 1.2% and 1.0%, respectively) to T4:T1 = 0.7 in 11 (0.6) and 8 (0.9) min (both P less than 0.001 vs spontaneous recovery).

Adult↗
PubMed1991

Cardiovascular changes at antagonism of atracurium. Effects of different doses of premixed neostigmine and glycopyrronium in a ratio of 5:1.

The cardiovascular changes in the 10 minutes following antagonism of an atracurium-induced block were studied in 32 patients. A 5:1 ratio combination of either 15, 35, 55 or 75 micrograms/kg neostigmine, with a corresponding dose of 3, 7, 11, or 15 micrograms/kg of glycopyrronium was used for antagonism. The least change in heart rate was with neostigmine 15 micrograms/kg with an increase of more than 15 beats/minute found in only one patient. Antagonism with 35, 55 and 75 micrograms/kg neostigmine mixture produced the greatest increase in heart rate at one minute and this was significantly different from the effect of the 15 micrograms/kg dose. Twenty out of 24 patients given the larger doses had heart rate increases in excess of 15 beats/minute and in nine patients this ranged from 30 to 52 beats/minute, representing increases of 46-80% above baseline values. Arterial pressure increases after antagonism were statistically significant in all four groups, with no between-group difference; these were clinically unimportant. When antagonising an atracurium-induced block with clinically useful doses of neostigmine, the standard 5 : 1 ratio combination with glycopyrronium will result in an initial tachycardia.

Anesthesia, General↗
PubMed1991

Antagonism of atracurium with neostigmine. Effect of dose on speed of recovery.

In 36 patients in whom anaesthesia was maintained with nitrous oxide and 0.5% isoflurane an atracurium-induced neuromuscular block was either allowed to recover spontaneously or antagonised with one of four doses of neostigmine (15 micrograms/kg, 35 micrograms/kg, 55 micrograms/kg or 75 micrograms/kg). The recovery times to a train-of-four ratio of 0.5, 0.75 and 0.9 were recorded. In patients given neostigmine, antagonism was at an average T1 of between 8.8% and 14.9%. There was no difference in the recovery times between the patients given neostigmine 35 micrograms/kg, 55 micrograms/kg or 75 micrograms/kg. Recovery after neostigmine 15 micrograms/kg was significantly slower than after the higher doses. One patient given neostigmine 75 micrograms/kg showed an unusual bimodal pattern of recovery. There appears to be no benefit in giving a larger dose than 35 micrograms/kg of neostogmine as a single bolus.

Adult↗
PubMed1990

Cardiovascular effects of doxacurium, pancuronium and vecuronium in anaesthetized patients presenting for coronary artery bypass surgery.

The cardiovascular effects of bolus doses of doxacurium 0.037 mg kg-1 were compared with those following equipotent doses of pancuronium (0.09 mg kg-1) and vecuronium (0.075 mg kg-1) and with those following high-dose doxacurium (0.075 mg kg-1), in patients with coronary artery disease. Anaesthetic technique comprised premedication with lorazepam, papaveretum and hyoscine, induction with diazepam, fentanyl, thiopentone, atropine and suxamethonium, and the trachea was intubated. At least 20 min later, during stable nitrous oxide in oxygen anaesthesia, a single bolus of neuromuscular blocking drug was administered and the effects measured at 1, 5 and 10 min. There was a small decrease in heart rate following doxacurium 0.075 mg kg-1, but no other significant or dose-related changes in mean heart rate, arterial pressure or cardiac index with doxacurium. Similar results were found following vecuronium, but the reduction in heart rate was more pronounced. In contrast, significant increases in mean arterial pressure, heart rate and cardiac index occurred after pancuronium.

Anesthesia, General↗