Junior doctors' hours. Alternative representative body is needed.
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Humans↗
Biomedical subjects
C Wong
Publications and source records attributed to C Wong.
Selection of bacteriophage T4 antimutator DNA polymerases: a link between proofreading and sensitivity to phosphonoacetic acid.
During DNA replication, DNA polymerases alternate between DNA synthesis and proofreading the newly synthesized DNA. In order to understand the molecular details of how DNA polymerases determine the balance between polymerase and proofreading activities, it would be useful to have mutants which switch between the two activities either more or less frequently. Antimutator DNA polymerases switch more frequently and thus have more opportunity for proofreading. We have observed that mutant DNA polymerases which proofread less frequently have a mutator phenotype and are inhibited by the pyrophosphate analogue phosphonoacetic acid. Sensitivity to phosphonoacetic acid can be used to isolate second-site suppressor mutations. These suppressor mutations encode amino acid substitutions which produce antimutator DNA polymerases.
Amino Acids↗
A pilot study to investigate the pulmonary effects of digoxin in patients with asthma.
AIM: A number of studies have shown that increased salt intake is associated with worsening asthma. The aim of this study was to investigate the respiratory effects of digoxin (a potent inhibitor of Na+K+ATPase) in patients with asthma. METHODS: Eight asthmatic patients were given digoxin (0.5 mg/daily) or matching placebo for 8 days. Treatments were assigned using a randomised double blind, crossover design. Bronchial hyperresponsiveness to methacholine, forced expiratory volume is one second (FEV1, serum potassium (K), urinary sodium and K, heart rate, blood pressure and the QTc interval of the ECG were measured on each treatment. RESULTS: When compared to placebo, digoxin significantly decreased FEV1 (p<0.03); the QTc interval (p<0.05), and increased serum K (p<0.02). There was a tendency for digoxin to increase bronchial hyperresponsiveness. CONCLUSION: In this small study digoxin resulted in a decline in spirometry. Further studies in a larger group of patients should be performed to assess this potentially adverse effect of digoxin.
Adult↗
A concept-based retrieval system for thoracic radiology.
Current digital information systems in radiology are insufficient to accommodate the retrieval needs of academicians. Significant efforts are required in retrieving clinical cases for teaching and research. We describe a prototype system that supports intelligent case retrieval based on a combined specification of patient demographics, radiologic findings, and pathologic diagnoses. The documents for these cases can be distributed among multiple heterogeneous data bases. The system features automatic indexing of radiology and pathology reports, a comprehensive lexicon for thoracic radiology, an interface to a hospital information system, radiology information system, and picture archiving and communication systems, and a graphical user interface for query formulation and results visualization. The prototype system was developed within the domain of thoracic radiology involving patients with lung cancer.
Abstracting and Indexing↗
Peripheral infusion as the route of choice for intravenous nutrition: a prospective two year study.
A central venous catheter (CVC) is widely regarded as the standard route for delivery of intravenous nutrition (IVN). Peripheral venous infusion avoids the morbidity of a CVC, but may require regular resiting of standard intravenous cannulae, or compromise of the nutritional quality of the feed, to avoid thrombophlebitis. Fine-bore catheters, designed for use in neonates, have been associated with a much lower incidence of phlebitis when used for peripheral IVN in adults, but reports have been limited to selected groups of patients. A prospective study of 302 courses of IVN is presented in which a peripheral vein was the route of first choice. The composition of the feed was determined by the patient's metabolic requirement, and was not compromised to facilitate peripheral venous infusion. In 51% of all courses of IVN the peripheral route alone was used; 76% of patients who received peripheral IVN required only one fine-bore catheter.
Journal Article↗
A study of the quality of life and cost-utility of renal transplantation.
The objective of this study was to assess the cost-utility of renal transplantation compared with dialysis. To accomplish this, a prospective cohort of pre-transplant patients were followed for up to two years after renal transplantation at three University-based Canadian hospitals. A total of 168 patients were followed for an average of 19.5 months after transplantation. Health-related quality of life was assessed using a hemodialysis questionnaire, a transplant questionnaire, the Sickness Impact Profile, and the Time Trade-Off Technique. Fully allocated costs were determined by prospectively recording resource use in all patients. A societal perspective was taken. By six months after transplantation, the mean health-related quality of life scores of almost all measures had improved compared to pre-transplantation, and they stayed improved throughout the two years of follow up. The mean time trade-off score was 0.57 pre-transplant and 0.70 two years after transplantation. The proportion of individuals employed increased from 30% before transplantation to 45% two years after transplantation. Employment prior to transplantation [relative risk (RR) = 23], graft function (RR 10) and age (RR 1.6 for every decrease in age by one decade), independently predicted employment status after transplantation. The cost of pre-transplant care ($66,782 Can 1994) and the cost of the first year after transplantation ($66,290) were similar. Transplantation was considerably less expensive during the second year after transplantation ($27,875). Over the two years, transplantation was both more effective and less costly than dialysis. This was true for all subgroups of patients examined, including patients older than 60 and diabetics. We conclude that renal transplantation was more effective and less costly than dialysis in all subgroups of patients examined.
Adult↗
Spermidine-condensed DNA and cone-shaped lipids improve delivery and expression of exogenous DNA transfer by liposomes.
A new liposome system containing spermidine-condensed DNA and negative cone-forming lipids designed to improve gene delivery and expression is described. The compacted nature of condensed DNA forms permitted a higher extent of encapsulation of DNA in liposomes. These vesicles contained fusogenic cone-shaped lipids to increase fusion between liposomes and membranes to enhance the amount of DNA delivery into the cells. In addition, the insensitivity of condensed DNA forms to endonucleases and restriction enzymes, as well as their higher activity in both replication and transcription, improve foreign DNA expression. These improvements in condensed DNA encapsulation in liposomes, transfer into the cells, and DNA expression increase the number of transfected cells and produce a higher level of gene expression in most transfected cells. This is reflected in the 60-fold cell culture transfection increase compared with traditional liposome transfection systems. This liposome system does not cause any apparent damage to the transfected cells; furthermore, the liposomes are small, 400-500 nm, and have negative surface charges that can prolong their circulation half-lives in vivo, permitting their use for in vivo gene therapy applications.
Animals↗
The frequency of venous thrombosis in cemented and non-cemented hip arthroplasty.
We randomised 250 patients undergoing unilateral, elective hip arthroplasty for osteoarthritis to receive either a cemented or a non-cemented Mallory Head prosthesis. Aspirin was used as prophylaxis against thromboembolism during the first half of the study and adjusted-dose warfarin during the second half. Postoperatively, all patients were asked to have bilateral venography and 80% agreed. All were evaluated clinically for pulmonary embolism. There was no difference in the frequency of deep-venous thrombosis between the two groups (50% cemented nu 47% non-cemented, p = 0.73; 95% CI of the difference -13.6% to 19.3%). Three of the 64 patients (5%) in whom venography had demonstrated isolated distal thrombi developed pulmonary emboli.
Aged↗
Characterization of aggregates of recombinant human factor VIII by size-exclusion chromatography and immunoassay.
The presence of aggregates of Factor VIII (FVIII) was assessed for a highly purified form (rFVIII) and for the formulated preparation containing human serum albumin (rFVIIIf). Size-exclusion chromatography (SEC) on Sepharose CL-6B and TSK 4000 matrices under native conditions revealed < 1% aggregates of FVIII in either rFVIII or rFVIIIf, as determined by FVIII immunoassay of chromatographic fractions. No degradation products were observed. The immunoassay was capable of detecting FVIII immunoreactivity to levels of approximately 5 ng/ml. Overlap of FVIII clotting (FVIII:c) and immunoassay (FVIII:cAg) activities was observed for SEC fractions. Heat stressing of rFVIIIf (47.5 degrees C for 24 h) resulted in a quantitative increase in FVIII-positive material in the void volume of a TSK 4000 column, demonstrating that aggregates of FVIII can be produced and detected by this method. We conclude that aggregates of FVIII in rFVIII and rFVIIIf constitute < or = 1% by the method described.
Animals↗
Safety and efficacy of elective stent implantation following rotational atherectomy in large calcified coronary arteries.
Rotational atherectomy is an effective transcatheter therapy for calcified coronary lesions. In large (> 3-mm) calcified coronary arteries, stent implantation following rotational atherectomy may further improve acute and especially, long-term benefit. To determine the safety and efficacy of this device synergy approach, we studied 24 consecutive patients undergoing this procedure electively in native coronary arteries. Procedural success was achieved in 100% without any major ischemic complications. There was also no incidence of subacute thrombosis or cardiac event during 30-day follow-up period. Thus, we conclude that elective stent implantation following rotational atherectomy in large, calcified coronary arteries is safe and results in excellent clinical benefit up to 30 days.
Aged↗
The role of midazolam-induced sedation in bone marrow aspiration/trephine biopsies.
This study was undertaken in 102 adult patients to evaluate the safety and efficacy of intravenous (i.v.) midazolam in the setting of bone marrow aspiration and trephine biopsy (BMAT). Combined local anaesthetic (LA) and sedation was used in 87% of patients and 13% received LA alone. Amnesia occurred in all sedated patients with only 9% experiencing a mild degree of post-procedure pain. This contrasted sharply with the non-sedated group, in whom 85% had intense pain during the biopsy followed by protracted local discomfort in approximately 54%. Drowsiness and some psychomotor impairment were the only notable sedation-related side-effects in approximately 20%. None required assisted ventilation. There was a resounding patient preference for BMAT with sedation. Considering the ease of use, safety and efficacy of i.v. midazolam, the availability of flumazenil as a reversal agent and the undoubted positive effects on quality of life, we would advocate using it in BMAT provided that there were no contraindications.
Adolescent↗
Adaptive mutation sequences reproduced by mismatch repair deficiency.
Adaptive reversions of a lac frameshift mutation in Escherichia coli are -1 deletions in small mononucleotide repeats, whereas growth-dependent reversions are heterogeneous. The adaptive mutations resemble instability of simple repeats, which, in hereditary colon cancer, in yeast, and in E. coli occurs in the absence of mismatch repair. The postulate that mismatch repair is disabled transiently during adaptive mutation in E. coli is supported here by the demonstration that the growth-dependent mutation spectrum can be made indistinguishable from adaptive mutations by disallowing mismatch repair during growth. Physiologically induced mismatch repair deficiency could be an important mutagenic mechanism in cancers and in evolution.
Bacterial Proteins↗
Electrophysiologic profile and efficacy of intravenous dofetilide (UK-68,798), a new class III antiarrhythmic drug, in patients with sustained monomorphic ventricular tachycardia. Dofetilide Arrhythmia Study Group.
There is increasing evidence that class III antiarrhythmic agents may be superior to class I agents for the long-term treatment of life-threatening ventricular tachyarrhythmias. This open study evaluated the acute electrophysiologic effects, antiarrhythmic efficacy, and safety of different doses of intravenous dofetilide, a new class III drug, in 50 patients with sustained monomorphic ventricular tachycardia inducible by programmed electrical stimulation who had previously been unsuccessfully treated with 0 to 7 (median 3) other drugs. Intravenous dofetilide was administered over 60 minutes at the following dose levels: 1.5, 3.0, 6.0, 9.0, and 15.0 micrograms/kg. Significant class III activity was apparent at doses of 3.0 to 15.0 micrograms/kg, as evidenced by dose-related prolongation of the QTc interval by 13.4% to 14.2%, ventricular effective refractory period by 7.9% to 20.6%, and ventricular functional refractory period by 7.3% to 25.0%. The corresponding mean +/- SD plasma dofetilide concentrations ranged from 1.45 +/- 0.52 to 6.48 +/- 1.31 ng/ml. There was no evidence of reverse use-dependence. At these electrophysiologically active dose levels, intravenous dofetilide suppressed (complete response) or slowed (partial response) inducible ventricular tachycardia in 17 of 41 patients (41%) compared with 0 of 9 patients receiving only 1.5 micrograms/kg. The response rate was fairly uniform among the groups receiving 3.0, 6.0, 9.0, and 15.0 micrograms/kg. Intravenous dofetilide was hemodynamically well tolerated. Torsades de pointes (which was self-limiting) developed in only 1 patient, who was allocated to receive 15.0 micrograms/kg. There were no other proarrhythmic episodes or serious adverse effects. Further evaluation of the therapeutic potential of dofetilide in the management of life-threatening ventricular arrhythmias is justified.
Aged↗
Junior doctors' hours. Committee response was ignorant.
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Humans↗
Characterization of the murine gene encoding the hyaluronan receptor RHAMM.
We describe the isolation and characterization of the murine gene encoding RHAMM, a hyaluronan receptor which regulates focal adhesion turnover, is required for cell locomotion and is a critical downstream regulator of ras transformation. The RHAMM gene spans at least 20 kb and comprises 14 exons ranging in size from 75 to 1099 bp. Primer extension studies indicate that the major transcription start point is in position -31, relative to the start Met. Northern blot analysis of mouse fibroblast RNA identified two hybridizing species of 4.2 and 1.7 kb. Comparison of cDNA clones and RT-PCR products with the genomic clones identified alternately spliced exons in both the coding and 5' noncoding regions of RHAMM. In the coding region exon 4 is alternately spliced. The major RHAMM transcript (RHAMM1) in 3T3 fibroblasts does not contain exon 4 and encodes a protein of 70 kDa. A minor transcript containing exon 4, namely RHAMM v4, encodes a 73-kDa protein, as demonstrated by isoform-specific antibodies. Western analysis demonstrated both a major 70-kDa (RHAMM 1) and minor 73-kDa RHAMM protein (v4) in 3T3 murine fibroblast cell lysates. The functional significance of these two isoforms is currently being investigated.
Amino Acid Sequence↗
Acid hydrolysis of monoclonal antibodies.
For analysis of monoclonal antibodies using polyacrylamide gel electrophoresis, two hydrolytic fragments derived from the heavy chain of mouse IgG1 were produced during incubation of the antibodies in Laemmli reducing sample buffer at 100 degrees C for 5 min. The cleavage sites were identified by amino terminal sequencing. Results indicate that the final pH of the mixture is critical for the production of the fragments which are generated when the pH is approximately 6.0. At pH 8.0, no fragments are detected. The relevance of this finding to those working with monoclonal antibodies is discussed.
Acids↗
Imported malaria in Auckland in 1993.
AIM: To determine the number of people with malaria in Auckland in 1993 and determine species, sources, exposure history, use of chemoprophylaxis, outcome and geographic attack rates. METHODS: We prospectively obtained the numbers of people with laboratory diagnosed malaria from all haematology departments in Auckland and then contacted the patients and their doctors to elicit further details. RESULTS: Forty three people, 30 men and 13 women, had malaria. Twenty eight were New Zealanders, 10 migrants, three temporary visitors and two not determined. Thirty two had P vivax infection, 11 P falciparum: none had complications. The highest attack rate was in travellers to the Solomon Islands. Eighty two per cent took prophylaxis. CONCLUSIONS: Malaria is an uncommon diagnosis in Auckland. Most patients took prophylaxis. The disease is undernotified. No one died of malaria in 1993 in Auckland.
Adolescent↗
Junior doctors' hours. Members of Junior Doctors Committee are in cloud cuckoo land.
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Humans↗