Biomedical subjects
D Hunt
Publications and source records attributed to D Hunt.
Nurses, nursing and health care. A personal view.
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The investigation of chest pain: audit and intervention.
OBJECTIVE: To examine the patterns of tests requested for patients admitted with chest pain, and to monitor the effects on those patterns of issuing a set of guidelines formulated by an expert panel. SETTING: Tertiary referral hospital (teaching). DESIGN: A retrospective audit of the patterns of testing of patients with chest pain compared with testing recommended by an expert panel, followed by comparison with patterns of testing after guidelines were issued. INTERVENTION: Practice guidelines, based on the expert committee's recommendations, were drawn up for use in the cardiology unit. OUTCOME MEASURES: Tests per admission, bed days per admission, emergency readmission rate. PATIENTS: Sixty-seven patients with diagnosis at the time of admission of chest pain and a discharge diagnosis of "intermediate coronary syndrome". RESULTS: The major finding of the audit was the excessive use of "biochemistry test profiles" instead of targeted tests as recommended by the expert committee. Intervention led to a decrease in the number of tests per admission in the cardiology unit from an average of 22.9 tests in the six months before intervention to 9.7 in the six months after (P < 0.001). There was no effect on bed days per admission or emergency readmission rates. CONCLUSION: Audit and intervention in a specialised unit of patients with a specified diagnosis led to more cost effective use of the resources of the Royal Melbourne Hospital Department of Biochemistry.
Degradation of rat C-reactive protein by macrophages.
Rat C-reactive protein (CRP) is a serum glycoprotein belonging to the 'pentraxin' family of proteins. In this study we have shown the specific binding of 125I-CRP to rat peritoneal macrophages at 4 degrees C. This binding was dependent upon incubation time, CRP and cell concentrations, and was not inhibited by either phosphorylcholine or human IgG. At 37 degrees C, the surface-bound 125I-CRP was internalized and degraded. The degradation of 125I-CRP was measured by the formation of 125I-labelled trichloroacetic-acid-soluble CRP peptides by either precipitation assays or by h.p.l.c. of the incubation medium using a gel-filtration column. Since chloroquine and leupeptin inhibited CRP degradation, it was concluded that degradation of CRP occurred in the lysosomal compartment of the macrophage. There was an absolute requirement for the presence of bivalent cations (Ca2+ and Mg2+) in the incubation medium for the binding and degradation of CRP, which could be inhibited by EDTA but not by phosphorylcholine or human IgG. H.p.l.c. analysis of the medium obtained from incubation of macrophages with 125I-CRP revealed the presence of 125I-labelled low-M(r) peptides, the formation of which was dependent upon incubation time.
Qualitative and quantitative studies of cytokines synthesized and secreted by non-human primate peripheral blood mononuclear cells.
Non-human primates are being utilized in a variety of pre-clinical studies, including those involved with mechanisms of organ transplant rejection and those being used as models to test the efficacy of vaccines against a variety of infectious diseases, most notably AIDS. These studies clearly involve immunological effector mechanisms, which include the interaction between T cells, B cells, monocytes, and cytokines that regulate these interactions. However, there is very little known about assays and quantitation of cytokines from non-human primates. In attempts to address this issue, bioassays, commercially available EIA kits, and primer pairs and probes specific for human cytokines were evaluated for their ability to detect and quantitate the non-human primate homologues. Data suggest that although the EIA kits that were evaluated for human IL-1 alpha, IFN-gamma, and TNF-beta failed, the EIA kits for IL-1 beta, IL-2, IL-4, IL-6, and TNF-alpha, the bioassays and RT-PCR assays for each of the cytokines were successful in detection and most likely quantitation of the non-human primate cytokine homologues. These assays will greatly facilitate future studies on the role of cytokines in these non-human primate studies.
Radiofrequency catheter ablation for paroxysmal supraventricular tachycardia: a report of 135 procedures.
BACKGROUND: Paroxysmal Supraventricular Tachycardia (PSVT) is a common condition which until recently has been treated with anti-arrhythmic drugs or surgery. Radiofrequency (RF) catheter ablation is a new mode of treatment which provides a cure of this condition. AIMS: To present our early experience of RF catheter ablation for PSVT. METHODS: One hundred and thirty-five procedures were performed in 117 patients. The diagnostic study and therapeutic catheter ablation were performed as a combined electrophysiological procedure in 74 patients (63%). In 58 patients (50%), PSVT was due to Atrio-ventricular junctional (nodal) re-entrant tachycardia (AVJRT). Twenty-five of the 58 patients underwent a fast pathway ablation while 33 had ablation of their slow pathway. The mean number of radiofrequency pulses delivered was ten for a mean duration of 25 seconds. Radiofrequency ablation of accessory pathways was attempted in 58 patients; pathways were left-sided in 29 patients, postero-septal in 21, midseptal in five, Mahaim connection in two, antero-septal in one and right free wall in one patient. One patient with incessant automatic atrial tachycardia also underwent a successful RF ablation. RESULTS: Using RF ablation cure of PSVT was achieved in 90% of patients. Cure of AVJRT was achieved in 95% (55/58) of patients using either fast or slow pathway ablation. Only one patient required permanent pacemaker implantation for Mobitz type I AV block following fast pathway ablation. The overall success rate for ablation of accessory pathways was 85%. There is an operator learning curve for this procedure suggested by the fact that the success rate for accessory pathway ablation at first attempt was 63% in the first 29 patients and 93% in the remaining 29. There was no significant morbidity or mortality during or after the procedure. In a mean follow-up of nine months in the patients with successful ablation only two patients with AVJRT had a recurrence of documented PSVT. Both these patients had successful repeat RF ablation. Catheter ablation using radiofrequency energy is an effective and safe therapeutic option for patients with symptomatic PSVT.
ISIS 5 possibilities.
There are five major therapeutic groups for possible evaluation in the ISIS 5 trial. They include intravenous beta-blocking agents, glucose-insulin-potassium (GIK) therapy, newer anticoagulant and antithrombotic agents (hirudin and Hirulog), newer thrombolytic drugs such as recombinant plasminogen activator (r-PA) and surfactant and emulsifying agents such as Rheothrx. Many pilot studies are underway. Selection of agents will depend on the scientific interest of collaborating hospitals as well as the agent's safety and efficacy.
Identification and regional localization of a highly polymorphic dinucleotide repeat D11S614 to the interval in 11q23.3 flanked by recurrent translocation breakpoints.
A highly informative dinucleotide repeat polymorphism has been identified at the D11S614 locus on chromosome 11q23. Ten different alleles have been observed at this locus, and the heterozygosity frequency is approximately 85%. Physical localization of this marker in a panel of somatic cell hybrids containing chromosome 11 translocations showed that it maps to 11q23.3, within the interval between the recurrent t(4;11) leukaemia breakpoint and the t(11;22) Ewing's sarcoma breakpoint. This physical mapping data is consistent with the genetic mapping which indicates tight linkage to other markers in the q23.3 region including PBGD, CD3D and D11S29. Regional localization of highly informative markers such as D11S614 will facilitate integration of the genetic and physical maps.
Malignant ventricular arrhythmias in patients with mitral valve prolapse and mild mitral regurgitation.
Mitral valve prolapse (MVP) is a common disorder that, in general, has a good prognosis. Rare occasions of sudden death have been reported in patients with MVP and it is presumed that the basis of sudden death is arrhythmic. We report seven patients with moderate to severe MVP and malignant ventricular arrhythmias. All patients had trivial to mild mitral regurgitation and normal left ventricular function. Three patients presented with syncope, two with out-of-hospital cardiac arrest, and three with recurrent palpitations and presyncope. In a mean follow-up period of 2.5 years (range 6 months to 5 years), two patients died suddenly despite successful control of their nonsustained ventricular tachycardia (VT) with sotalol as shown by ambulatory monitoring. Two patients, who had sustained VT despite antiarrhythmic drug therapy, had mitral valve surgery, however, monomorphic VT could be induced in both even after surgery. The arrhythmias in the remaining three patients are controlled on antiarrhythmic drugs. We conclude that a selected subset of patients with MVP, malignant ventricular arrhythmias, and mild mitral regurgitation are at risk of sudden death. Syncope, inferolateral repolarization changes, complex ventricular ectopy, and a markedly myxomatous valve may be pointers to higher risk of sudden death and mitral valve surgery may not provide control of ventricular arrhythmias.
Antigen mimicry in autoimmune disease sharing of amino acid residues critical for pathogenic T cell activation.
A nonamer peptide from murine nicotinic acetylcholine receptor delta chain (ACR delta), which shared four amino acid residues with a nonamer peptide of murine ovarian zona pellucida glycoprotein ZP3, induced murine autoimmune oophoritis and IgG autoantibody to the zona pellucida. Crossreaction between the ACR delta and ZP3 peptides was established by the response of a ZP3 peptide-specific, oophoritogenic T cell clone to both peptides in association with IA (alpha k beta b). By substituting the ZP3 peptides with a single alanine, four amino acids within the ZP3 peptide were found to be important for ovarian autoimmune disease, autoantibody response, and stimulation of the ZP3-specific T cell clone. Substitution with conservative amino acids of three residues also ablated activity, whereas the fourth, a phenylalanine, was replaceable by tyrosine without loss of activity. Of the four critical amino acids, three were shared between the ZP3 peptide and the ACR delta peptide. Moreover, polyalanine peptides with the four critical ZP3 amino acids or the four amino acids common to the ZP3 and ACR delta peptides induced immune response to ZP3 and elicited severe ovarian autoimmune disease. Thus, organ-specific autoimmune disease can occur through immune response against unrelated self (or foreign) peptides that share with a self-peptide sufficient common amino acid residues critical for activation of pathogenic, autoreactive T cells.
Clinical experience with surgery for paroxysmal supraventricular tachycardia: a report of 103 cases.
One-hundred-and-three patients underwent surgery for paroxysmal supraventricular tachycardia (PSVT). In eighty-three patients (81%), PSVT was due to an accessory atrioventricular pathway (Group I) and in 20 (19%) to Atrioventricular Junctional (AV nodal) Reentrant Tachycardia (AVJRT:Group II). Initial surgery successfully divided 77 of 83 accessory pathways, including 58 of 60 left free wall pathways, 12 of 15 posteroseptal pathways, six of seven right free wall pathways and one anteroseptal pathway. Twenty patients had successful surgery for AVJRT. Surgery was performed with low morbidity and no early or late mortality in either group. One patient in each group required permanent pacemaker implantation. Immediate (within one week) postoperative electrophysiological study using epicardial wires was performed in 96% of patients and repeat electrophysiological study six months later was possible in 65/103 (63%) patients. Patients with surgery for accessory pathways were followed-up for a mean 34 +/- 23 months, while those with surgery for AVJRT for a mean of 13 +/- seven months. No patient with successful surgery has had a clinical recurrence of PSVT. Thus the results indicate that surgery is a safe and curative therapy for patients with PSVT.
Immediate and long-term results of percutaneous balloon aortic valvuloplasty: a report of 33 procedures.
The purpose of this study was to evaluate the immediate and long-term clinical and haemodynamic effects of Percutaneous Balloon Aortic Valvuloplasty (PBAV). Thirty-three procedures were performed in 27 patients, 11 males and 16 females with a mean age of 72 years. The peak to peak systolic gradient across the aortic valve decreased by 52%, from 67 +/- 24 mmHg to 31 +/- 15 mmHg (p < 0.0001) and the aortic valve area increased by 35%, from 0.48 +/- 0.16 to 0.67 +/- 0.21 cm2 (p < 0.001) after PBAV. There were no procedural deaths. Minor complications occurred in seven patients. Eighty-one per cent of patients (27 procedures) showed immediate symptomatic improvement, five remained symptomatic and one died in hospital before discharge. In a mean follow-up of 17 +/- 12 months (range six to 38 months), eight patients died due to congestive cardiac failure, six underwent repeat PBAV, three died due to noncardiac causes and three had recurrent symptoms controlled on medical therapy. Event free survival at 15 months was 43%. In conclusion PBAV produces a satisfactory immediate clinical and haemodynamic result, however, considering the high rate of symptom recurrence, this procedure has a beneficial role only in short-term palliation of severely symptomatic patients who are unable to undergo aortic valve replacement.
Coronary-pulmonary artery fistula arising distal to obstructive coronary lesions.
We report 2 cases of coronary-pulmonary artery fistulae (CPF) arising distal to obstructive coronary artery disease. The fistula in the first patient was in the form of a tortuous dilatation of the distal portion of the right coronary artery and opened into the right pulmonary artery. In the second case, the fistula, a plexus of vessels, arose from the left anterior descending artery and entered the left pulmonary artery. Both the fistulae were successfully ligated at the time of concurrent coronary artery bypass graft surgery.
Single coronary artery: a report of 2 cases.
An isolated single coronary artery is a rare congenital anomaly. We report 2 patients each of whom had a single coronary artery with an obstructive atherosclerotic lesion in one of its branches. In the first patient angioplasty was successfully performed using a perfusion catheter whilst in the second, the procedure was considered inappropriate as the patient had chronic total occlusion.
Heparin-binding serum protein(s) is required for the protection of sialyltransferase released during the incubation of rat jejunal slices.
Incubation of rat jejunal slices in Krebs-Ringer bicarbonate buffer (KRB) required the presence of heat-inactivated horse serum (HHS) in order to show time-dependent release of sialyltransferase into the medium. Sialyltransferase activity could not be detected in the medium when KRB alone or KRB supplemented with either albumin or glycerol was used in the incubations. The viability of the jejunal slices for up to 4 h of incubation was determined by studying the incorporation of glucosamine and leucine into acid-insoluble proteins. Supplementation of KRB with HHS had no beneficial effect on the rate of incorporation of leucine and glucosamine into proteins. KRB medium obtained after different periods of incubation contained higher trypsin-like activity than KRB medium containing HHS. Various antiproteases present as supplements to KRB resulted in the release of sialyltransferase activity from the jejunal slices. Among these antiproteases, alpha 1-proteinase inhibitor (alpha 1-PI) was the most effective. Also, HHS added to KRB immediately following incubation resulted in partial restoration of sialyltransferase activity in the medium, suggesting the presence of anti-proteolytic factors in HHS. The addition of increasing concentrations of heparin to incubations containing HHS caused a decrease in the medium sialyltransferase activity. The heparin-binding fraction (HBF) from HHS, when added to incubations, was able to protect the sialyltransferase released into medium. However, HHS depleted of its heparin-binding fraction by heparin-agarose affinity chromatography was unable to protect the sialyltransferase. HBF was separated into high- and low-molecular-mass fractions (fractions A and B respectively) by gel-filtration chromatography. The capacity to protect the released sialyltransferase was contained in fraction B. Fraction A contained multiple bands on SDS/PAGE and did not protect the enzyme. Fraction B contained a major protein band on the gel which corresponded to the migration of a similar band in human alpha 1-PI. HBF as well as fraction B isolated from HHS showed anti-trypsin-like activity. The results presented indicate that HHS contains a heparin-binding protein(s) similar to human alpha 1-PI which plays a role in the protection of sialyltransferase released from jejunal slices.
Ventricular dysfunction following direct-current shock atrioventricular junction ablation.
Catheter-induced His bundle ablation for refractory supraventricular arrhythmias is most commonly performed with direct-current shock energy of 200-300 joules. The high energy pulse delivered by direct-current shock produces a lesion in the atrioventricular node by fulguration, with the residual energy being dissipated as a pressure wave. The effect of direct-current shock His bundle ablation on global and regional ventricular function was assessed in 14 consecutive patients by radionuclide ventriculography performed before and after ablation and again three months later. All studies were performed with ventricular pacing at 110 bpm. Global left ventricular ejection fraction was found to be significantly reduced at the three month study (0.43 +/- 0.03 vs 0.50 +/- 0.03, pre ablation, p = 0.02). A significant reduction in wall-motion score was also seen in six of the seven patients who had normal wall motion in pacing rhythm prior to ablation. Deterioration was mainly seen at the left and right ventricular apices. The observed reduction in ventricular function that follows direct-current shock His bundle ablation may result from myocardial damage from electro-coagulation or from barotrauma and supports continued investigation into alternative, less traumatic energy sources for the procedure.
The evolutionary war. Open forum.
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