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R M Jones

Publications and source records attributed to R M Jones.

At least 109 records · Page 6Linked to original sources
PubMed1994

Purification and properties of porphobilinogen deaminase from Arabidopsis thaliana.

Porphobilinogen deaminase (EC 4.3.1.8) has been purified to homogeneity (16,000-fold) from the plant Arabidopsis thaliana in yields of 8%. The deaminase is a monomer of M(r) 35,000, as shown by SDS/PAGE, and 31,000, using gel-filtration chromatography. The pure enzyme has a Vmax. of 4.5 mumol/h per mg and a Km of 17 +/- 4 microM. Determination of the pI and pH optimum revealed values of 5.2 and 8.0 respectively. The sequence of the N-terminus was found to be NH2-XVAVEQKTRTAI. The deaminase is heat-stable up to 70 degrees C and is inhibited by NH3 and hydroxylamine. The enzyme is inactivated by arginine-, histidine- and lysine-specific reagents. Incubation with the substrate analogue and suicide inhibitor, 2-bromoporphobilinogen, results in chain termination and in inactivation.

Amino Acid Sequence↗
PubMed1994

An evaluation of laparoscopic versus open cholecystectomy.

OBJECTIVE: To compare open cholecystectomy (OC) with laparoscopic cholecystectomy (LC) in terms of clinical aspects and a limited review of costs. SETTING: The Austin Hospital, Melbourne, a university teaching hospital. DESIGN: Prospective LC patients were compared with a retrospective group of OC patients whose surgery had been performed by the same surgeons. METHODS: Consecutive patients undergoing LC were interviewed, their medical records were analysed and the cost of their hospitalisation was assessed. Similar data, collected previously from patients undergoing OC, were used for comparison. RESULTS: There were 108 patients in each group, 93.5% treated electively. All had gallstones. No deaths or common bile duct injury occurred. The mean operating room time was 131 +/- 3.7 minutes for OC and 164 +/- 4.7 minutes for LC. Operative cholangiography was attempted in 80% in each group, being successful when attempted in all OCs and in 95% of LCs. The conversion rate of LCs to OCs was 4.5%. Minor complications were more frequent with OCs. The mean duration of hospital stay was 6.5 +/- 0.3 days for OCs and 2.0 +/- 0.2 days for LCs. The amount and period of analgesia were significantly less in the LC group. Patients recovered significantly faster after LC (P < 0.01) during the first eight weeks after surgery. There was no difference by 12 weeks. The overall cost for each LC was $838 less than OC for the entire hospital stay. CONCLUSION: These results support the view that LC is a safe and justified replacement for OC in the elective situation, with benefits to the patient, hospital and general community. The hospital cost for LC was less than for OC.

Adolescent↗
PubMed1994

Comparison of desflurane and fentanyl-based anaesthetic techniques for coronary artery bypass surgery.

We have compared, in 51 ASA II and III patients undergoing coronary artery bypass surgery, an inhaled anaesthetic technique based on desflurane, supplemented with low-dose (10 micrograms kg-1) fentanyl, with an i.v. technique using high-dose (50 micrograms kg-1) fentanyl with midazolam for induction. Satisfactory records were available for analysis in 50 patients. There were no differences between groups in operating time, cardiopulmonary bypass time, aortic cross-clamp time or duration of stay in the intensive care unit after surgery. Desflurane maintained mean systemic arterial pressure at the awake level during incision and sternotomy (end-tidal concentrations 3.7% and 4.6%, respectively) but decreased it significantly at all other times. With fentanyl, mean systemic arterial pressure was unchanged from awake values during induction and laryngoscopy but increased significantly at incision and sternotomy by 8% and 12.8%, respectively, to exceed the desflurane group at sternotomy by 20 mm Hg (P < 0.001). With desflurane, heart rate remained at 60-67 beat min-1 at all times before cardiopulmonary bypass. This was always lower than the fentanyl group by 5-15 beat min-1 and the difference was significant at induction, during skin preparation and before aortic cannulation. In comparison with the desflurane group, cardiac index was significantly greater in the fentanyl group at induction, laryngoscopy and during skin preparation, but was significantly less before aortic cannulation. The need for vasodilator intervention was significantly more common in the fentanyl group before, during and after cardiopulmonary bypass and for beta adrenoceptor block before cardiopulmonary bypass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Safety and potency of ANQ 9040 in male volunteers.

BACKGROUND: ANQ 9040 is an experimental nondepolarizing neuromuscular relaxant. Initial investigations in animals had indicated a rapid onset of action comparable to that of succinylcholine. The purpose of this study was to assess the safety and potency of ANQ 9040 in humans. METHODS: ANQ 9040 was assessed in 41 male volunteers. Anesthesia was induced with propofol and maintained with a propofol infusion and 60% N2O/40% O2. Neuromuscular function was measured by mechanomyography using train-of-four stimulation of the ulnar nerve every 12 s. After an initial pilot study, 23 volunteers received a single dose of ANQ 9040 of between 0.5 and 1.1 mg/kg to determine the dose-response relationship. The final 10 volunteers were given twice the estimated ED95 of ANQ 9040 as a single bolus dose. RESULTS: The estimated ED50 and ED95 of ANQ 9040 were 0.6 and 1.3 mg/kg, respectively. Apart from an increase in heart rate, no important adverse effects were noted after ANQ 9040 administration in the dose range 0.5-1.1 mg/kg. In the volunteers who received 2.6 mg/kg ANQ 9040, a substantial increase in plasma histamine was observed. This was associated with a 12% decrease in mean arterial pressure and a 49% increase in heart rate. In this group, the mean onset time to neuromuscular block was 51.3 s. CONCLUSIONS: ANQ 9040 is a rapid-onset neuromuscular blocking agent. However, twice the ED95 dose is associated with significant histamine release and tachycardia. This finding suggests that this drug will not be useful in clinical practice.

Adolescent↗
PubMed1994

Hepatic artery anatomy in relation to reconstruction in liver transplantation: some unusual variations.

The anatomy of the hepatic artery and its variations were studied in 70 donor livers harvested for liver transplantation in the Austin Hospital. Forty three (61.5%) had a 'normal' vascular anatomy and 27 (38.5% had anomalous anatomy. The anomalies were single in 13 instances and multiple in 14 and involved the origin of the right or left hepatic arteries or the coeliac axis. The hepatic artery was reconstructed most frequently by end-to-end anastomosis of the donor to the recipient common hepatic artery (79%). A Carrel patch, an interposition aortic graft and the donor superior mesenteric artery were other techniques used for reconstruction. Two patients (3%) had a postoperative hepatic artery thrombosis, with one of those patients having a further reconstruction. When one vascular anomaly is found, there is a high probability of others being present. The authors' experience confirms that safe hepatic arterial anastomosis can be performed even in the presence of abnormalities of the vascular arterial system.

Adolescent↗
PubMed1994

In vitro potency and mode of action of ANQ9040: a novel fast acting muscle relaxant.

1. The in vitro potency and mode of action of the novel, rapid-onset steroidal relaxant ANQ9040 were characterized in the rat isolated phrenic nerve hemidiaphragm. 2. At 32 degrees C, ANQ9040 antagonized neurally evoked contractures with EC50s of 21.5 microM for unitary twitches; 14.4 microM for 2 Hz 'trains of four'; and 7.5 microM for 50 Hz (2 s) tetanic stimulus trains. 3. (+)-Tubocurarine was 22-24 times more potent than ANQ9040 in comparative organ bath experiments. 4. Intracellular recording from endplates revealed that ANQ9040 (0.53-10.0 microM) dose-dependently and reversibly decreased the amplitude of miniature-endplate potentials (IC50 of circa 0.95 microM) without changing transmembrane potential. 5. Surmountable antagonism of subthreshold responses to exogenous (ionophoretic) acetylcholine provided evidence for a non-depolarizing and competitive blockade of post-junctional nicotinic receptors. 6. Sucrose gap recordings of phrenic nerve action potentials revealed that, at concentrations up to 32 microM, ANQ9040 produced no tonic or frequency-dependent antagonism of axonic Na+ channels. 7. We conclude that ANQ9040 is a relatively low-affinity, non-depolarizing, nicotinic antagonist. The in vitro results are discussed in relation to factors impinging on relaxant kinetics and current models for frequency-dependent fade.

Action Potentials↗
PubMed1994

Patterns of coagulopathy during liver transplantation: experience with the first 75 cases using thrombelastography.

Using both conventional laboratory clotting profile and thrombelastography, coagulation status was monitored intraoperatively during liver transplantation in the first 75 cases performed at the Austin Hospital between June 1988 and October 1992. Superimposed on a baseline coagulopathy due to liver disease is a specific pattern of coagulation disturbance which occurs during a liver transplant. Fibrinolysis occurs in the anhepatic stage, worsens with early reperfusion and then spontaneously resolves. In addition reperfusion is associated with a transient clotting defect. If blood loss is excessive, coagulopathy due to massive transfusion may compound the situation. Thrombelastography is a measurement technique allowing rapid on-site assessment of functional clotting status. It is particularly useful in liver transplant surgery. In combination with clinical bleeding assessment it facilitates selective use of component therapy (fresh frozen plasma, platelets and cryoprecipitate) and specific drug treatment only when it is appropriate. It also acts as a liver function test, being especially useful in assessing the graft after reperfusion.

Blood Coagulation↗
PubMed1994

Blood loss and transfusion requirements in liver transplantation: experience with the first 75 cases.

The blood loss data and transfusion requirements including blood bank, salvaged washed red cells, fresh frozen plasma and cryoprecipitate were analysed for the first 75 cases of liver transplantation performed at the Austin Hospital between June 1988 and October 1992. The mean blood loss was 8.8 litres (standard deviation 14.1) with a median value of 4.0 litres. Blood product use expressed as mean number of units (SD) was bank red blood cells 7.1 (12.7), washed red blood cells 3.9 (5.9), fresh frozen plasma 7.1 (9.1), platelets 5.1 (7.4), and cryoprecipitate 1.7 (5.1). These results demonstrate that liver transplantation can be performed without imposing excessive demands on blood transfusion services. Management should include surgical techniques to minimize bleeding and use of autologous transfusion. Use of component therapy (FFP, platelets and cryoprecipitate) should not be empirical. It should be selective on the basis of clinical bleeding assessment and guided by results of the laboratory coagulation profile and changes in thrombelastographic (TEG) parameters.

Adolescent↗
PubMed1993

Purification and properties of the uroporphyrinogen decarboxylase from Rhodobacter sphaeroides.

Uroporphyrinogen decarboxylase (EC 4.1.1.37) was purified 600-fold from Rhodobacter sphaeroides grown anaerobically in the light. The enzyme, under both denaturing and non-denaturing conditions, is a monomer of M(r) 41,000. The Km values are 1.8 microM and 6.0 microM for the conversion of uroporphyrinogen I and III to coproporphyrinogen I and III respectively. The enzyme is susceptible to inhibition by both uroporphyrinogen and uroporphyrin. The pH optimum is 6.8 and the isoelectric point is 4.4. The importance of cysteine and arginine residues is implicated from studies with inhibitors. The sequence of the first 29 amino acids of the N-terminus shows a high degree of similarity to the primary structures of other uroporphyrinogen decarboxylases. Studies on the order of decarboxylation of the four acetic acid side chains of uroporphyrinogen III suggest that at high substrate levels a random route is preferred.

Amino Acid Sequence↗
PubMed1993

Anti-tumor activity of a blocked ricin immunotoxin with specificity against the cluster-5A antigen associated with human small-cell lung cancer.

The monoclonal antibody (MAb SEN31, a mouse IgG1 which recognizes the cluster-5a antigen on small-cell lung cancer (SCLC) cells, was used to prepare a selective and potent blocked ricin immunotoxin. In a series of experiments in vitro and in a SCLC xenograft model in nude mice, the tumor localization potential of the radiolabeled antibody SEN31 and the anti-tumor activity of the immunotoxin SEN31-bR, the non-specific binding activity of which had been greatly reduced by blocking of the galactose binding domains of the B-chain, was determined. Radiolabeling of SEN31 was performed by linking a 67Ga-labeled desferrioxamine moiety to the oligosaccharide side chains of the antibody in order to preserve the specific cell-binding activity. 67Ga-SEN31 bound to the antigenic sites on cells of the SW2 SCLC cell line, with a dissociation constant of 3.5 nM and, when injected i.v., selectively localized at the site of s.c.-growing SW2 tumor xenografts in nude mice, with a tumor-to-blood ratio of 3.5. The immunotoxin SEN31-bR was potently and selectively active against SCLC cell lines both of classic and of variant morphologies. At a concentration of 300 pM the immunotoxin selectively eliminated 4.5 logs of clonogenic tumor cells. In nude mice, SEN31-bR was cleared from the blood with biphasic kinetics following i.v. injection and maintained a stable serum level during continuous i.p. infusion. The growth of s.c. SW2 solid-tumor xenografts was delayed following a single i.v. injection or a continuous i.p. infusion, each at a non-toxic dose.

Animals↗
PubMed1993

Early detection and measurement of experimental myocardial infarcts with horseradish peroxidase.

Current methods of experimental infarct size measurement require tissue analysis several hours after the ischemic event. Electron microscopy identifies irreversibly injured myocytes early after ischemia, but cannot be used to measure myocardial infarct size. Horseradish peroxidase (HRP), a tracer protein that permeates the disrupted sarcolemma of injured myocytes, was used to determine infarct size. New Zealand White rabbits (n = 15) were subjected to 30 min coronary artery occlusion and 24 h reperfusion. Prior to euthanasia, HRP was administered intravenously. The hearts were excised, perfused with triphenyl tetrazolium chloride (TTC), and perfusion fixed. A frozen section was cut from left ventricular slices, and the brown HRP reaction product was developed with 3,3'-diaminobenzidine tetrahydrochloride and H2O2. The areas delineated by intramyocyte HRP (as a percent of the left ventricle) closely correlated with infarct size determined by conventional hematoxylin-eosin (H&E) stain and TTC (means +/- S.E.M.): 29.5 +/- 3.0% vs 27.6 +/- 2.9% vs 28.6 +/- 2.6%, respectively. The coefficient of correlation between HRP and H&E was 0.94. This method was tested for early infarct detection in rabbits subjected to 30 min coronary occlusion followed by intravenous injection of HRP and sacrifice. HRP-delineated infarcts measured 21.4 +/- 3.7% of the left ventricle, and electron microscopic examination from ischemic and non-ischemic areas was used to confirm that cells containing HRP were irreversibly injured. Thus, HRP can be used to accurately measure myocardial infarct size in experimental coronary artery occlusion and reperfusion in infarcts as early as 30 min after coronary occlusion or following 24 h of reperfusion.

Animals↗
PubMed1993

Activity of doramectin against nematode endoparasites of cattle.

A series of 28 controlled anthelmintic studies, involving 634 cattle, was conducted throughout North America and Europe to evaluate the efficacy of doramectin against a broad range of gastrointestinal parasitic nematode species and lungworms in naturally and experimentally infected animals. Within each study, one or two groups were treated with doramectin at 200 micrograms kg-1 and another group received no drug treatment. Worm burdens were estimated by standardised techniques, and efficacy assessed on reduction of worm burdens in doramectin-treated animals. Doramectin was at least 99.6% effective (P < 0.0002) in eliminating the immature and adult stages of the following 14 species of nematodes: Ostertagia ostertagi (including inhibited), Ostertagia lyrata, Haemonchus placei, Trichostrongylus axei, Trichostrongylus colubriformis, Cooperia oncophora (including inhibited), Cooperia pectinata, Cooperia punctata, Cooperia spatulata, Cooperia surnabada, Bunostomum phlebotomum, Strongyloides papillosus, Oesophagostomum radiatum and Dictyocaulus viviparus. Efficacy against adult Trichostrongylus longispicularis, Nematodirus spathiger and Trichuris spp. was 93.1%, 96.5% and 94.6%, respectively. Efficacies against adult and fourth-stage larvae of Nematodirus helvetianus, the dose-limiting species, were 73.3% and 75.5%, respectively.

Animals↗
PubMed1993

High-dose oral acyclovir reduces the incidence of cytomegalovirus infection in liver transplant recipients.

To determine the impact of high-dose oral acyclovir on cytomegalovirus (CMV) infection or disease after liver transplantation, CMV cultures were prospectively collected for 6 months after transplantation. The incidence and timing of infection and disease in patients receiving high-dose oral acyclovir (3200 mg/day) from day 7 until 3 months after transplantation were compared with an historical control group who received no acyclovir. All patients who did not receive acyclovir (group 1, n = 12) but only 57% of those who did (group 2, n = 22) had CMV infection (P = .008). Nine (75%) group 1 but only 3 (14%) group 2 patients had positive leucocyte cultures (P = .0007). Three group 1 patients developed CMV disease; 1 group 2 patient developed CMV hepatitis. Each of these 4 patients had CMV viremia (P = .01). The frequency of CMV infection after liver transplantation appears to be reduced by high-dose oral acyclovir.

Acyclovir↗
PubMed1993

The effectiveness of pre-operative advice to stop smoking: a prospective controlled trial.

Patients who smoke cigarettes suffer increased postoperative morbidity. A prospective, controlled trial was designed to evaluate the effectiveness of written pre-operative advice to stop smoking before admission for elective surgery and to record the duration of abstinence immediately before the operation. Although the advice was ineffective in persuading patients to stop smoking, it was associated with a reduction in the amount of tobacco consumed. Nicotine and carbon monoxide have important short-term adverse effects but 15% of all patients continued to smoke within an hour of surgery. If patients are unable to give up cigarette smoking completely, it is still worthwhile stopping on admission to hospital.

Humans↗