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N Buckley

Publications and source records attributed to N Buckley.

At least 19 recordsLinked to original sources
PubMed2006

Interventions for paracetamol (acetaminophen) overdose.

BACKGROUND: Poisoning with paracetamol (acetaminophen) is a common cause of hepatotoxicity in the Western World. Inhibition of absorption, removal from the vascular system, antidotes, and liver transplantation are interventions for paracetamol poisoning. OBJECTIVES: To assess the benefits and harms of interventions for paracetamol overdose. SEARCH STRATEGY: We identified trials through electronic databases, manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies until December 2005. SELECTION CRITERIA: Randomised clinical trials and observational studies were included. DATA COLLECTION AND ANALYSIS: The primary outcome measure was all-cause mortality plus liver transplantation. Secondary outcome measures were clinical symptoms, (eg, hepatic encephalopathy, fulminant hepatic failure), hepatotoxicity, adverse events, and plasma paracetamol concentration. We used Peto odds ratios and odds ratios with 95% confidence intervals (CI) for analysis of outcomes. Random- and fixed-effects meta-analyses were performed. MAIN RESULTS: Ten small and low-methodological quality randomised trials, one quasi-randomised study, and 48 observational studies were identified. It was not possible to perform relevant meta-analyses of randomised trials that have addressed our outcome measures. Activated charcoal, gastric lavage, and ipecacuanha are able to reduce the absorption of paracetamol, but the clinical benefit is unclear. Of these, activated charcoal seems to have the best risk-benefit ratio. N-acetylcysteine seems preferable to placebo/supportive treatment, dimercaprol, and cysteamine, but N-acetylcysteine's superiority to methionine is unproven. It is not clear which N-acetylcysteine treatment protocol offers the best efficacy. No strong evidence supports other interventions for paracetamol overdose. N-acetylcysteine may reduce mortality in patients with fulminant hepatic failure (Peto OR 0.26, 95% CI 0.09 to 0.94, one trial). Liver transplantation has the potential to be life saving in fulminant hepatic failure, but refinement of selection criteria for transplantation and long-term outcome reporting are required. AUTHORS' CONCLUSIONS: Our results highlight a paucity of randomised trials on interventions for paracetamol overdose. Activated charcoal seems the best choice to reduce absorption. N-acetylcysteine should be given to patients with overdose but the selection criteria are not clear. No N-acetylcysteine regime has been shown to be more effective than any other. It is a delicate balance when to proceed to liver transplantation, which may be life-saving for patients with poor prognosis.

Acetaminophen↗
PubMed2002

Interventions for paracetamol (acetaminophen) overdoses.

BACKGROUND: Self-poisoning with paracetamol (acetaminophen) is a common cause of hepatotoxicity in the Western World. Interventions for paracetamol poisoning encompass inhibition of absorption, removal from the vascular system, antidotes, and liver transplantation. OBJECTIVES: The objective was to assess the beneficial and harmful effects of interventions or combination of interventions for paracetamol overdose. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, MEDLINE, EMBASE, and text searches were combined (until July 2001). SELECTION CRITERIA: Randomised clinical trials (RCTs) and observational studies as well as human volunteer randomised trials were included. The studies could be unpublished or published as an article, an abstract, or a letter and no language limitations were applied. DATA COLLECTION AND ANALYSIS: All the analyses were performed according to the intention to treat. The methodological quality of the included trials was evaluated by components of methodological quality. MAIN RESULTS: Nine RCTs (all small and of low methodological quality), one quasi-randomised trials, 37 observational studies, and nine randomised trials including human volunteers were identified. It was impossible to perform meta-analyses including more than two RCTs. Activated charcoal, gastric lavage, and ipecacuanha are able to reduce the absorption of paracetamol but the clinical benefit is unclear. Of these, activated charcoal seems to have the best risk-benefit ratio. N-acetylcysteine seems preferable to placebo/supportive treatment (relative risk of mortality in patients with fulminant hepatic failure = 0.65; 95% confidence interval 0.43 to 0.99), dimercaprol, and cysteamine, but N-acetylcysteine's superiority to methionine is unproven. It is not clear which N-acetylcysteine treatment protocol offers the best efficacy. No evidence supports haemoperfusion or cimetidine for paracetamol overdose. Liver transplantation has the potential to be life saving in fulminant hepatic failure, but further refinement of selection criteria for liver transplantation and evaluation of the long-term outcome are required. REVIEWER'S CONCLUSIONS: This systematic Review has highlighted a paucity of RCTs on interventions for paracetamol overdose. Activated charcoal seems the best choice to reduce paracetamol absorption. N-acetylcysteine should be given to patients with paracetamol overdose. No N-acetylcysteine regime has been shown to be more effective than any other. It is a delicate balance when to proceed to liver transplantation, which may be life saving in patients with a poor prognosis. Interventions for paracetamol overdose need assessment in high-quality, multi-centre RCTs.

Acetaminophen↗
PubMed2002

Oximes in acute organophosphorus pesticide poisoning: a systematic review of clinical trials.

BACKGROUND: Acute organophosphorus (OP) pesticide poisoning is widespread in the developing world. Standard treatment involves the administration of intravenous atropine and an oxime to counter acetylcholinesterase inhibition at the synapse, but the usefulness of oximes is uncertain. AIM: To assess the evidence on the use of oximes in OP poisoning. DESIGN: Systematic review. METHODS: We searched Medline, Embase, and Cochrane databases (last check 01/02/02) for 'organophosphate' or 'oxime' together with 'poisoning' or 'overdose'. We cross-referenced from other articles, and contacted experts to identify unpublished studies. A Web search engine [www.google.com] was also used, with the keywords 'organophosphate', 'oxime', and 'trial' (last check 01/02/02). RESULTS: We found two randomized controlled trials (RCTs) involving 182 patients treated with pralidoxime. The RCTs found no benefit with pralidoxime, and have been used to argue that pralidoxime should not be used in OP poisoning. DISCUSSION: The RCT authors must be congratulated for attempting important studies in a difficult environment. However, their studies did not take into account recently clarified issues regarding outcome, and their methodology is unclear. A generalized statement that pralidoxime should not be used in OP poisoning is not supported by the published results. Oximes may well be irrelevant in the overwhelming self-poisoning typical of the tropics, but a large RCT comparing the current WHO-recommended pralidoxime regimen (>30 mg/kg bolus followed by >8 mg/kg/h infusion) with placebo is needed for a definitive answer. Such a study should be designed to identify any patient subgroups that might benefit from oximes.

Acute Disease↗
PubMed2000

Sedation and analgesia in adult patients: evaluation of a staged-dose system based on body weight for use in abdominal interventional radiology.

PURPOSE: To evaluate the safety and effectiveness of a systematic protocol for sedation and analgesia in interventional radiology. MATERIALS AND METHODS: Ninety-one adult patients underwent 113 abdominal interventional procedures. Fentanyl citrate and midazolam hydrochloride were administered in one to five steps (A, B, C, D, E) until the patient was drowsy and tranquil at the effective loading dose (ELD). Doses per step were as follows: A, fentanyl 1 microg per kilogram of body weight; B, midazolam 0.010-0.035 mg/kg; C, repeat dose in A; D, repeat half the dose in B; and E, midazolam 1-2-mg boluses (maximum, 0.15 mg/kg). RESULTS: The ELD was reached in no procedure after step A, in 70 after B, in 23 after C, and in 18 after D. Step E was needed in two procedures. The mean maximum pain score (scale of 0 to 10) was 3.4; pain scores in 85 (75%) procedures were 4 or less (discomforting). Severe pain occurred in seven (6%) procedures. Hypoxia (oxygen saturation < 90%) occurred in 11 (22%) procedures performed in patients breathing room air and four (6%) performed in those breathing supplemental oxygen (P: =.04). All patients responded to supplemental oxygen. CONCLUSION: This stepwise "ABCDE protocol" allows safe and effective sedation of patients. It is easy to use and may be useful in training radiology residents, staff, and nurses in the techniques of sedation and analgesia. Supplemental oxygen should be used routinely.

Adolescent↗
PubMed1999

Phenotypic consequences resulting from a methionine-to-valine substitution at position 48 in the HPr protein of Streptococcus salivarius.

In gram-positive bacteria, the HPr protein of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) can be phosphorylated on a histidine residue at position 15 (His(15)) by enzyme I (EI) of the PTS and on a serine residue at position 46 (Ser(46)) by an ATP-dependent protein kinase (His approximately P and Ser-P, respectively). We have isolated from Streptococcus salivarius ATCC 25975, by independent selection from separate cultures, two spontaneous mutants (Ga3.78 and Ga3.14) that possess a missense mutation in ptsH (the gene encoding HPr) replacing the methionine at position 48 by a valine. The mutation did not prevent the phosphorylation of HPr at His(15) by EI nor the phosphorylation at Ser(46) by the ATP-dependent HPr kinase. The levels of HPr(Ser-P) in glucose-grown cells of the parental and mutant Ga3.78 were virtually the same. However, mutant cells growing on glucose produced two- to threefold less HPr(Ser-P)(His approximately P) than the wild-type strain, while the levels of free HPr and HPr(His approximately P) were increased 18- and 3-fold, respectively. The mutants grew as well as the wild-type strain on PTS sugars (glucose, fructose, and mannose) and on the non-PTS sugars lactose and melibiose. However, the growth rate of both mutants on galactose, also a non-PTS sugar, decreased rapidly with time. The M48V substitution had only a minor effect on the repression of alpha-galactosidase, beta-galactosidase, and galactokinase by glucose, but this mutation abolished diauxie by rendering cells unable to prevent the catabolism of a non-PTS sugar (lactose, galactose, and melibiose) when glucose was available. The results suggested that the capacity of the wild-type cells to preferentially metabolize glucose over non-PTS sugars resulted mainly from inhibition of the catabolism of these secondary energy sources via a HPr-dependent mechanism. This mechanism was activated following glucose but not lactose metabolism, and it did not involve HPr(Ser-P) as the only regulatory molecule.

Alkaline Phosphatase↗
PubMed1997

The addition of continuous intravenous infusion of ketorolac to a patient-controlled analgetic morphine regime reduced postoperative myocardial ischemia in patients undergoing elective total hip or knee arthroplasty.

This double-blind randomized trial assessed the effect of adding an intravenous continuous infusion of ketorolac to a patient-controlled analgesia (PCA) morphine regimen on analgesia, heart rate, arterial blood pressure, and postoperative myocardial ischemia. Patients having elective total hip or knee replacement were randomized to receive ketorolac 30 mg bolus, followed by an infusion of 5 mg/h for 24 h or placebo. All patients had access to PCA morphine (20 microg/kg bolus, with a lockout of 6 min). Patients were monitored for pain visual analog scale, blood pressure, heart rate, and ST segment depression via a continuous Holter monitor. ST depression of 1 mm 60 ms after the J point was considered significant if it lasted more than 1 min. There was no difference in demographics, risk factors, or cardiac medications between the groups. Ketorolac-treated patients had significantly better pain control at 2, 6, and 24 h. There was significant morphine sparing at all times after 3 h. There was no difference in the number of ischemic events between the groups. The ischemic episodes of the patients who received ketorolac occurred at slower heart rates (97 +/- 15 vs 114 +/- 16 bpm, P = 0.001) than those of patients in the placebo group. The duration of ST depression was shorter in ketorolac-treated patients (24 +/- 35 vs 76 +/- 95 min, P < 0.05). All ST depressions were clinically silent. Logistic regression of factors predicting ischemia included the use of calcium channel blockers and low pain score. These results suggest that analgesia with ketorolac reduces the duration of ischemic episodes in the first 24 h postoperatively.

Aged↗
PubMed1995

GSTM1 and CYP2D6 genotype frequencies in patients with pituitary tumours: effects on P53, ras and gsp.

We describe studies to determine if susceptibility to pituitary tumours is associated with the putatively high risk GSTM1 null and CYP2D6 EM genotypes. Frequency distributions of these genotypes were similar in cases and controls though the frequency of CYP2D6 PM and GSTM1 B tended to be lower (P = 0.072 and P = 0.095 respectively) in the tumour group. Immunopositivity for p53 was found in 18/97 tumours. In these samples GSTM1 null (39%) and CYP2D6 EM (56%) frequencies were not different to those in controls. The frequencies of CYP2D6 PM and GSTM1 B in the p53 immunonegative tumours tended to be lower (P = 0.055 and P = 0.1185 respectively) than in controls. Mutations in gsp and ras were studied using the polymerase chain reaction and allele specific oligonucleotide analysis. Eight of 19 somatotrophinomas demonstrated mutations in gsp; frequencies of GSTM1 null and CYP02D6 EM were similar to controls. No ras mutations were identified in 55-tumour studies. The data indicate the GSTM1 null and CYP2D6 EM genotypes are not associated with altered expression of p53 or, mutation of gsp and ras in these adenomas and, suggest the CYP2D6 PM genotype is associated with a reduced risk of pituitary adenomas and, that GSTM1*B confers greater protection than GSTM1*A.

Adult↗
PubMed1995

Clinical and genetic changes in a case of a Cushing's carcinoma.

A 30-year-old presented in 1984 with a clinically nonfunctional tumour which subsequently developed into a metastatic corticotrophinoma from which he died despite surgery in 1984, 1986 and 1991 and external radiotherapy in 1986. Molecular genetic analysis of tumour and metastatic tissue revealed loss of heterozygosity at loci on the autosomes 1p, 3p, 10q26, 11q13 and 22q12. Tissue taken at surgery in 1986 also revealed positive cytoplasmic immunostaining for p53 protein. No such staining was evident in tissue taken at first surgery in 1984. Further analysis of invasive pituitary adenomas may reveal loci associated with such behaviour, enabling better prediction of subsequent clinical outcome than is possible using standard histological techniques, and delivery of early, aggressive treatment to those tumours which show molecular markers associated with a poor prognosis.

Adenoma↗
PubMed1995

P53 protein accumulates in Cushings adenomas and invasive non-functional adenomas.

The p53 protein, a negative regulator of cell growth, plays an important role in the pathogenesis of many human tumours following gene mutation and/or deletion. We screened a large number of sporadic pituitary tumours for p53 protein accumulation suggestive of gene mutation. Samples were divided into benign adenomas (n = 95) and invasive tumours with local or distant invasion (n = 26). All main tumour classes were represented. Putative p53 mutations were detected by immunohistochemistry on paraffin-embedded sections using polyclonal CM-1 and monoclonal DO-7 and PAb1801 antibodies. Results were compared to normal post-mortem pituitary tissue controls (n = 17). p53 protein accumulation was detected in invasive tumours (16%), but only in corticotrophinomas (2/4) and non-functional tumours (4/15). In non-invasive adenomas, protein accumulation was observed only in ACTH-secreting tumours where 50% were positive (16/32). No protein accumulation was identified in any control tissue. These results indicate that p53 protein accumulation may play a role in the development of Cushings adenomas and in the progression of non-functional tumours to the invasive state.

Adenoma↗
PubMed1994

Calcium channel blocking drug overdose: an Australian series.

1. A descriptive case study of calcium channel-blocking drug (CCB) overdoses in the Hunter Region of NSW was performed to analyse the in-hospital morbidity and mortality of CCB drug overdoses in an Australian population. 2. The patients were admitted to major hospitals within the Hunter Region and treated initially with gastrointestinal decontamination, including the use of oral activated charcoal. Further management was required in most cases and included intravenous calcium, atropine and inotropic support. 3. Of the 15 CCB overdoses, four patients died. Noncardiogenic pulmonary oedema occurred in two other cases. Cardiac conduction defects occurred in 11 cases. 4. Atropine was found to be effective only after intravenous calcium had been administered. 5. Overdose with slow-release verapamil required prolonged treatment with intravenous calcium salts. 6. Overdose with verapamil or diltiazem in doses greater than 300 mg carries a significant risk of death and potentially life threatening arrhythmias occur with lower doses. 7. Recommended initial management includes early, effective gastrointestinal decontamination. High dose intravenous calcium salts should be given to reverse hypotension and bradycardia. Atropine and inotropic support are frequently required.

Adolescent↗