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Biomedical subjects

J M Hunter

Publications and source records attributed to J M Hunter.

At least 37 records · Page 2Linked to original sources
PubMed1999

Anaesthesia for Conn's syndrome.

We describe the peri-operative management of two patients undergoing bilateral adrenalectomy for Conn's syndrome; one using an open surgical approach and the other a laparoscopic technique. The first patient, aged 64 years, died of a myocardial infarction 5 days postoperatively; the second, aged 29 years, had an uneventful recovery. The pre-operative preparation, peroperative management and postoperative care of these patients are detailed, and the pathophysiology and clinical management of Conn's syndrome are reviewed.

Adrenalectomy↗
PubMed1999

Antagonism of rapacuronium using edrophonium or neostigmine: pharmacodynamics and pharmacokinetics.

We have studied the pharmacodynamics and pharmacokinetics of rapacuronium (Org 9487) in 70 healthy patients. Neuromuscular transmission was monitored using TOF stimulation of the ulnar nerve and mechanomyography of the adductor pollicis muscle. Half of the patients were given a single dose of rapacuronium 1.5 mg kg-1 and the remainder rapacuronium 1.5 mg kg-1 with three incremental doses of 0.5 mg kg-1, each given when T1/T0 had recovered to 25%. In all patients, neuromuscular block was antagonized using neostigmine 0.05 mg kg-1 or edrophonium 1.0 mg kg-1 (allocated randomly), 2 min after the final dose of rapacuronium. All patients developed complete block after rapacuronium 1.5 mg kg-1. Mean onset time was 66 (SD 24) s. In patients who received an antagonist 2 min after the first dose of rapacuronium, time to recovery of T1/T0 to 25% was similar after neostigmine (9.8 (3.8) min) and edrophonium (10.3 (4.3) min): in patients who received incremental doses of rapacuronium, spontaneous recovery of T1/T0 to 25% after the first dose was 18.9 (4.7) min. In those who received an antagonist 2 min after the first dose of rapacuronium, times to recovery of T4/T1 to 0.7 were also similar after neostigmine (23.7 (7.7) min) and edrophonium (29.1 (10.7) min). After three incremental doses of rapacuronium, there was a longer time to recovery of T1/T0 = 25% after neostigmine compared with edrophonium (5.1 (1.0) vs 3.3 (1.3) min; P < 0.05) but more rapid recovery to T1/T0 = 75% (10.1 (2.9) vs 16.8 (10.1) min; P < 0.05) and T4/T1 = 0.7 (19.8 (6.3) vs 35.1 (10.4) min; P < 0.05). A three-compartment pharmacokinetic model was justified. Typical values for clearance and initial volume of distribution (V1) were 4.4 ml kg-1 min-1 and 94.8 ml kg-1, respectively. In females, clearance was decreased by 38.5% compared with males and V1 was decreased by 25% in patients aged more than 65 yr.

Adolescent↗
PubMed1999

Clinical pharmacokinetics of the newer neuromuscular blocking drugs.

The pharmacokinetics of 6 new neuromuscular blocking drugs are described. These are the aminosteroids pipecuronium bromide, rocuronium bromide and rapacuronium bromide (ORG-9487) and the benzylisoquinolinium diesters doxacurium chloride, mivacurium chloride and cisatracurium besilate. In healthy individuals, these drugs all have similar volumes of distribution. Their pharmacokinetics are influenced little by age or anaesthetic technique, but renal and hepatic disease may significantly alter their distribution and elimination. Pipecuronium resembles pancuronium in its pharmacokinetic and neuromuscular blocking profile, but is devoid of cardiovascular effects. It has a low clearance (0.16 L/h/kg) and long elimination half-life (120 minutes). It is largely eliminated through the kidney. Rocuronium has a similar pharmacokinetic profile to vecuronium but its onset of action is more rapid and duration of action slightly shorter. Its clearance (0.27 L/h/kg) is intermediate between those of pipecuronium and rapacuronium, but its elimination half-life is long (83 minutes). The pharmacokinetics of rocuronium are altered by renal and hepatic disease; the latter probably has the more significant effect. Rapacuronium has a rapid onset, and a bolus dose has a short duration of action. It has a high clearance (0.59 L/h/kg) but a long elimination half-life (112 minutes). Doxacurium has a pharmacokinetic and pharmacodynamic profile similar to pipecuronium. It has a high potency and is devoid of cardiovascular effects. In adults, it has a low clearance (0.15 L/h/kg) and long elimination half-life (87 minutes). Mivacurium is a mixture of 3 stereoisomers. It has a short to intermediate duration of action. It is hydrolysed by plasma cholinesterase. Inherited or acquired alterations in plasma cholinesterase activity are associated with changes in the pharmacokinetics and time course of action of mivacurium. The 2 active isomers (cis-trans and trans-trans) have a high clearance (4.74 L/h/kg) and very short elimination half-lives (approximately 2 minutes). Cisatracurium is the 1R-cis 1'R-cis isomer of atracurium. It has similar pharmacokinetics and pharmacodynamics to atracurium. It is mainly broken down by Hofmann (non-enzymatic) degradation. Cisatracurium has an intermediate clearance (0.3 L/h/kg) and short elimination half-life (26 minutes). Hepatic and renal disease have little effect on its pharmacokinetics.

Aging↗
PubMed1998

75 years ago.

Explore the source record for details and available documents.

Anesthesia↗
PubMed1997

Cryogenic frozen solution matrixes for analysis of DNA by time-of-flight mass spectrometry.

We present an alternative matrix system for mass analysis of high molecular weight biomolecules by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). Single-stranded DNA oligomers are embedded in thin films of frozen solutions containing photoabsorbing substituted phenols. Ultraviolet laser desorption from these cryogenically cooled matrixes generates internally colder ions than from the equivalent room-temperature crystalline matrixes containing no solvent, as evidenced by a substantial reduction in the extent of fragmentation in the corresponding mass spectra of oligonucleotides. Furthermore, the homogeneity of the frozen solution samples allows analyte signals to be obtained uniformly throughout the sample. Sensitivity and mass resolution approaching that obtained using the most effective room-temperature crystalline matrix for DNA (3-hydroxypicolinic acid) are consistently and reproducibly obtained in both positive and negative ion mass spectra. As fragmentation is a principle factor limiting the maximum attainable mass resolution in MALDI-TOF mass analysis of DNA, this improvement in generating intact DNA ions is advantageous.

DNA↗
PubMed1997

Bore holes and the vanishing of guinea worm disease in Ghana's upper region.

Ghana's Upper Region provides an excellent example of the beneficial effects of improved water security provided by hand-pump tube wells. Following a Ghana-Canada bilateral development project that installed some 2500 pumps, protection rates against guinea worm disease may be estimated as 88% in the west, and 96% in the east. Survey comparisons between ca 1960 and 1990 show that dracunculiasis declined in 32 of a total of 38 areas. The shadow of guinea worm has been lifted from the land and, in many areas, a true "vanishing" has occurred. The few areas of disease increase are characterized by the lowest population densities, pioneer settlement for cotton farming, and an absence of bore holes. Vagaries of development have inadvertently produced disease transformations or "metamorphoses" from dracunculiasis to elephantiasis (lymphatic filariasis) in one area, and to red water disease (schistosomiasis hematobium) in other areas. Correlative associations between pump densities and guinea worm disease are weakened by the large size of areas for which disease is reported in 1990. One preliminary finding is that geographical distance to the pump is a stronger influence than demographic pressure on pumps, regarding dracunculiasis. Diminishing returns on higher pump densities in many areas support the idea of making fuller, safer use of supplementary non-pump water. Despite crises of fee payment and pump maintenance, the rural bore hole project has struck a mortal blow against guinea worm, and permanently raised the quality of life in the Upper Region.

Animals↗
PubMed1997

The pharmacokinetics and pharmacodynamics of rocuronium in patients with hepatic cirrhosis.

AIMS: To determine the effects of hepatic cirrhosis on the pharmacodynamics and pharmacokinetics of rocuronium bromide. METHODS: We studied 21 healthy patients and 17 patients with mild or moderate cirrhosis (Child-Pugh Class A and B). Patients were premedicated with diazepam orally; anaesthesia was induced with fentanyl and thiopentone, and maintained with isoflurane 0.6% (end-tidal) and nitrous oxide 66% in oxygen. The compound action potential of the adductor pollicis muscle in response to supramaximal stimulation of the ulnar nerve was recorded using the train-of-four (TOF) twitch technique. A bolus dose of rocuronium 0.6 mg kg(-1) was then given. Venous blood samples were taken for up to 8 h, and plasma rocuronium concentrations determined by h.p.l.c. RESULTS: The time to onset of neuromuscular block and maximal block achieved did not differ between the two groups. The mean (s.d.) recovery times were prolonged in the cirrhotic compared with the healthy group: 25% recovery T1:T0, 53.7 (18.1) vs 42.3 (14.2) min; 50% recovery T1:T0, 73.9 (33.9) vs 52.6 (19.8) min; 75% recovery T1:T0, 84.2 (24.5) vs 66.8 (27.2) min (all P<0.05); recovery of T4:T1 to 70%, 114.9 (31.7) vs 76.1 (28.8) min (P<0.01). A pharmacokinetic and pharmacodynamic model was fitted to the data for each patient. Three compartments were used to model the pharmacokinetic data; an effect compartment was added to model the pharmacodynamic data. Plasma clearance was significantly reduced in the cirrhotic group (2.66 (0.60) vs 3.70 (1.03) ml kg(-1) min (-1); P<0.005). The central (V1) and steady state volumes of distribution (V(ss)) did not differ significantly between the groups. The slow redistribution (t1/2,lambda1) and elimination (t1/2,z) half-lives were both significantly prolonged in cirrhosis (28.3 (12.1) vs 16.8 (4.6) min, P < 0.005; and 143 (80) vs 92 (40) min, P < 0.05 respectively). The exit rate constant for the effect compartment k(eo) was significantly increased in the cirrhotic group (0.25 (0.18) vs 0.16 (0.06) min(-1); P < 0.05), but cirrhosis had no significant effect on the parameters of the concentration-effect relationship Cp(ss)(50) and gamma. CONCLUSIONS: Hepatic elimination is an important pathway in the clearance of rocuronium, and delayed disposition causes the effect to be prolonged.

Adult↗
PubMed1997

A comparison of cisatracurium (51W89) and atracurium by infusion in critically ill patients.

OBJECTIVE: To evaluate and compare the safety and efficacy of cisatracurium (51W89) and atracurium administered by continuous infusion to critically ill patients requiring neuromuscular blocking agents to facilitate mechanical ventilation. DESIGN: Open, randomized, multicenter study of patients receiving cisatracurium or atracurium infusion to facilitate mechanical ventilation. SETTING: Five university teaching hospital intensive care units in the United Kingdom. PATIENTS: Sixty-one adult patients requiring neuromuscular blocking agents to facilitate mechanical ventilation. INTERVENTIONS: Bolus doses followed by continuous infusions of cisatracurium or atracurium were administered. Onset, maintenance, and recovery of neuromuscular blockade were measured, using transcutaneous ulnar nerve stimulation and an accelerometer. MEASUREMENTS AND MAIN RESULTS: Forty patients received cisatracurium (mean duration 48.1 +/- 4.2 [SEM] hrs), and 21 patients received atracurium (mean duration 46.1 +/- 5.8 hrs). The infusion rate for patients receiving cisatracurium was 3.1 +/- 0.2 microg/kg/min, and for patients receiving atracurium 10.4 +/- 0.9 microg/kg/min. There were no significant differences in mean times to 70% recovery of Train-of-Four ratio (cisatracurium 60 mins, atracurium 57 mins), although there was considerable interpatient variation (20 to 175 mins with cisatracurium vs. 35 to 85 mins with atracurium). One patient who received cisatracurium exhibited intermittent bronchospasm during and after the study period. CONCLUSIONS: Cisatracurium, an isomer of atracurium, appears to be a suitable agent for providing muscle relaxation in critically ill patients.

APACHE↗
PubMed1997

A comparison of the infusion pharmacokinetics and pharmacodynamics of cisatracurium, the 1R-cis 1'R-cis isomer of atracurium, with atracurium besylate in healthy patients.

We have compared the pharmacokinetics of cisatracurium with atracurium when given by bolus dose followed by continuous infusion. Twenty healthy patients were anaesthetised with thiopentone, midazolam, fentanyl and 70% nitrous oxide in oxygen. Ten patients (Group C) were randomly allocated to receive cisatracurium 0.1 mg.kg-1 and 10 patients (Group A) were given atracurium 0.5 mg.kg-1. Neuromuscular block was monitored using a mechanomyograph. When the first twitch of the train-of-four had recovered to 5% of control, an infusion of cisatracurium 3 micrograms.kg-1.min-1 was started in Group C and an infusion of atracurium 10 micrograms.kg-1.min-1 was started in Group A. The infusion rates were adjusted to maintain the first twitch of the train-of-four at 5% of control. The times to 90% and maximum depression of the first twitch of the train-of-four were significantly longer after cisatracurium than atracurium (2.2 and 3.4 min compared with 1.3 and 1.8 min, respectively; p < 0.01 in each instance). No significant differences were found in recovery parameters between the two groups. Blood samples were taken at regular intervals following the bolus, during the infusion and for 8 h thereafter. The plasma samples were analysed using high-performance liquid chromatography for cisatracurium and atracurium (using a method which distinguishes between the three geometric isomer groups), laudanosine and monoquaternary alcohol. The results were analysed using the Non-linear Mixed Effects Model program. A two-compartment model was fitted to the data. The different isomer groups of atracurium have different pharmacokinetics, the trans-trans group having the highest clearance (1440 ml.min-1) and the cis-cis group the lowest (499 ml.min-1). The clearance of cisatracurium (425 ml.min-1) is less than that of cis-cis atracurium and its elimination half-life is longer (34.9 min and 21.9 min, respectively). The plasma concentration of laudanosine after cisatracurium was one-fifth of that after atracurium.

Adult↗
PubMed1996

An introduction to guinea worm on the eve of its departure: dracunculiasis transmission, health effects, ecology and control.

A broad ranging discussion of the basic nature of guinea worm disease, fused with personal field observations in Ghana, shows its long-overlooked serious clinical aspects, and the many environmental and social influences that explain its persistence in the face of control efforts. It is a disease of neglect par excellence in remote rural areas. The global eradication campaign (which is not reviewed here) may be expected to come to closure over the next half decade. This account offers an overview, synthesis, and interpretation of a fascinating example in disease ecology at the time of its global vanishing.

Community Participation↗
PubMed1996

Comparison of the pharmacodynamics and pharmacokinetics of an infusion of cis-atracurium (51W89) or atracurium in critically ill patients undergoing mechanical ventilation in an intensive therapy unit.

We have studied 12 critically ill, sedated patients who required a neuromuscular blocking drug to assist mechanical ventilation in an intensive care unit. Patients were randomized to receive an infusion of cis-atracurium 0.18 mg kg-1 h-1 (group 1, n = 6) or atracurium 0.6 mg kg-1 h-1 (group 2, n = 6) preceded, if necessary, by a bolus dose of 2 x ED95 of the same drug (cis-atracurium 0.1 mg kg-1 or atracurium 0.5 mg kg-1). Neuromuscular block was monitored using an accelerograph and the infusion rate adjusted regularly so that it was possible to detect the first response to train-of-four (TOF) stimulation of the ulnar nerve at the wrist. Blood samples were obtained for estimation of plasma cis-atracurium and laudanosine concentrations (group 1) or the three groups of atracurium isomers and laudanosine (group 2). There was no apparent haemodynamic or allergic response to either drug. The mean infusion time in group 1 was 37.6 h and in group 2, 27.5 h. On termination of the infusion, the time for the TOF ratio to reach 0.7 was similar in the two groups (group 1 = 60 min; group 2 = 62 min). The mean infusion rate of cis-atracurium was 0.19 mg kg-1 h-1 and of atracurium 0.47 mg kg-1 h-1 (expressed as mg of bis-cation): cis-atracurium was 2.5 times more potent than atracurium. Using the NONMEM program, a single compartment pharmacokinetic model was fitted to the plasma concentrations of cis-atracurium and the cis-cis, cis-trans and trans-trans isomers of atracurium. The mean population pharmacokinetic values for cis-atracurium were: volume of distribution (V) = 21,900 (SEM 416) ml; clearance (Cl) = 549 (79) ml min-1; half-life (T1/2) = 27.6 (3.6) min; and for the three groups of atracurium isomers were: cis-cis, V = 15,100 (720) ml, Cl = 449 (42) ml min-1, T1/2 = 23.4 (1.2) min; cis-trans, V = 18,000 (667) ml, Cl = 1070 (43) ml min-1, T1/2 = 11.7 (0.1); trans-trans, V = 13,100 (1280) ml, Cl = 1560 (55) ml min-1, T1/2 = 5.8 (0.4) min. Plasma laudanosine concentrations were lower in the cis-atracurium (peak value 1.3 micrograms ml-1) than in the atracurium (maximum 4.4 micrograms ml-1) group.

Adult↗
PubMed1996

Anaesthesia in the elderly. Special considerations.

The physiological effects of aging may alter the pharmacokinetics and pharmacodynamics of many anaesthetic drugs. Premedicants should be avoided in the very old, and intravenous induction agents given in reduced dosage. The new inhalational agents, desflurane and sevoflurane, may be useful in this patient group; sevoflurane can also be administered to induce anaesthesia. However, both these agents can have adverse cardiovascular effects at high concentrations. The nondepolarising neuromuscular blocking drug, atracurium, is useful in the elderly because it does not undergo organ disposition. It may, however, cause histamine release, with resultant hypotension and tachycardia. It is as yet uncertain whether the isomer of atracurium, cisatracurium, will have any advantages in this age group, but it appears to be free from histamine-releasing effects. If residual neuromuscular block is antagonised in the elderly, then the dosage of anticholinesterase should be titrated using neuromuscular monitoring, as these agents can have adverse effects in this age group. Postoperative analgesia requires careful control in the elderly. Several methods of administration exist for relieving pain in this age group, but each has disadvantages. Anaesthesia in the elderly therefore requires skill and judgement based on these physiological and pharmacological considerations.

Aged↗