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C J Ellis

Publications and source records attributed to C J Ellis.

At least 37 records · Page 2Linked to original sources
PubMed1998

Thrombolytic eligibility.

The Fibrinolytic Therapy Trialists' Collaborative Group has demonstrated that patients without clear contraindications who present with ischaemic chest pain within 12 hours of the onset of symptoms and who have ST segment elevation or bundle branch block on their electrocardiogram (ECG), will benefit from thrombolytic therapy. Therefore the treatment of patients presenting with ischaemic chest pain is guided by the initial ECG. This paper addresses the question of thrombolytic eligibility in several subsets of patients who may benefit from treatment. It also explores the data which confirm the benefit for patients presenting with an inferior myocardial infarction and for those presenting from six-12 hours after the onset of symptoms. In conclusion, thrombolytic therapy should not be routinely withheld from diabetic or elderly patients, menstruating women and patients who have had cardiopulmonary resuscitation.

Age Factors↗
PubMed1998

Hirudin (desirudin) and Hirulog (bivalirudin) in acute ischaemic syndromes and the rationale for the Hirulog/Early Reperfusion Occlusion (HERO-2) Study.

Unlike unfractionated heparin, direct thrombin inhibitors such as hirudin and Hirulog inhibit clot-bound as well as fluid-phase thrombin, escape neutralisation by platelet secretion products, do not require monitoring, and are unassociated with immune thrombocytopenia. They have been shown to have modest advantages over heparin when given after thrombolytic therapy, reducing reinfarction by 14%. In the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO 2b) trial, patients treated with streptokinase and adjunctive hirudin had a reduction in death or myocardial infarction of 40% at 30 days (8.6% with hirudin versus 14.4% with heparin, p = 0.004). In the Hirulog Early Reperfusion/Occlusion (HERO 1) trial, 48% of patients who received Hirulog as adjunctive therapy with streptokinase had Thrombolysis in Myocardial Infarction (TIMI) trial grade 3 flow in the infarct-related artery, compared with 35% of patients who received heparin with streptokinase (p < 0.05). The HERO 2 study, involving 17,000 patients, will test the hypothesis that Hirulog and aspirin given before streptokinase will reduce mortality compared with aspirin plus heparin. Early administration of direct thrombin inhibitors may potentially improve the outcome of patients treated with thrombolytic therapy.

Aged↗
PubMed1998

Low molecular weight heparins in acute ischaemic syndromes.

Thrombus formation and ongoing generation play a major role in the pathogenesis of unstable angina and myocardial infarction (MI). Unfractionated heparin is widely used as an adjunctive therapy in the management of acute ischaemic syndromes, but it has a number of limitations including inter-patient variability, need for monitoring, and the fact that its use may be associated with thrombocytopenia. Low molecular weight heparins have pharmacological and pharmacokinetic properties that may result in better clinical outcomes and safety. They are easy to administer and do not require monitoring. Low molecular weight heparins have been shown to reduce mortality and the incidence of MI and recurrent ischaemia compared with placebo in patients with unstable angina and non-Q-wave MI, and have a more predictable anticoagulant effect than standard unfractionated heparin. They also can be used long term in the outpatient setting, in the form of self-administered subcutaneous injections. The clinical relevance of these new developments is still being defined in ongoing clinical trials and cost-effectiveness analyses.

Angina, Unstable↗
PubMed1998

New antiplatelet agents.

Aspirin is an established therapy for the management of acute myocardial infarction (AMI) and unstable angina. Secondary prevention with chronic aspirin therapy is also indicated for patients with stable angina. Aspirin inhibits cyclo-oxygenase-I, a key enzyme in the biosynthetic pathway leading to the production of thromboxane A2. It therefore inhibits only one of the many activation pathways leading to platelet aggregation. Other antiplatelet agents that have also been evaluated in clinical trials include ticlopidine and clopidogrel, which inhibit adenosine diphosphate-mediated platelet aggregation, but these agents are known to be effective against only one of the 90 known agonists that stimulate platelet aggregation. The final common pathway for platelet aggregation involves the glycoprotein IIb/IIIa receptor combining with fibrinogen. Several inhibitors of the glycoprotein IIb/IIIa receptor have been developed and have an important role as adjunctive therapy in angioplasty. Recent trials have been performed in patients with unstable angina, and trials of adjunctive therapy are currently underway in patients receiving thrombolysis for AMI, and for secondary prevention. These drugs have various different features, including specificity for blockade of the glycoprotein IIb/IIIa receptor, half life, duration of the haemostatic effect and potential for antigenicity. Recently concluded and ongoing trials of both intravenous and oral agents are expected to provide further support for the introduction of these agents into clinical management of patients with acute coronary syndromes.

Abciximab↗
PubMed1998

The corrected TIMI frame count. The new gold standard?

Over the last decade Thrombolysis in Myocardial Infarction (TIMI) flow grades have been the gold standard for the assessment of efficacy of infarct-artery reperfusion. However, with the introduction of core angiographic laboratories, the reproducibility of TIMI flow grades has been questioned. The corrected TIMI frame count (CTFC) has been developed as a more reproducible method of quantifying infarct artery blood flow after myocardial infarction (MI). We have utilised the CTFC in two studies to examine infarct-artery blood flow. In the Hirulog in Early Reperfusion and Occlusion (HERO 1) study, the CTFC was measured at 90-120 minutes after administration of aspirin, streptokinase and either Hirulog or heparin. Only 27% of patients had a normal CTFC (< or = 27) in the infarct-related artery. Patients with a prolonged CTFC (> 27) had more abnormal left ventricular function (LVF) as measured by the mean chord score in the 'area at risk' (-2.51 vs -2.06, p = 0.02), on left ventriculography. In a second study, infarct-artery flow was examined four weeks and one year after MI. At four weeks, only 43% of patients with patient infarct-related arteries had a 'normal' CTFC of < or = 27. A prolonged CTFC at four weeks was a univariate predictor of increased reocclusion at one year (p = 0.001). CTFCs are frequently abnormal in patent infarct-related arteries, and predict reocclusion. Whether frame counting is a better predictor of late clinical outcomes than the TIMI flow grade needs to be prospectively examined in large clinical trials.

Blood Flow Velocity↗
PubMed1998

Fecal hydrogen sulfide production in ulcerative colitis.

OBJECTIVE: Sulfide, a product of sulfate-reducing bacteria, has been proposed to play an etiologic role in ulcerative colitis. Ulcerative colitis feces have increased numbers and activity of sulfate-reducing bacteria, but only modestly increased sulfide. However, fecal sulfide exists largely in the volatile, highly toxic H2S form that moves rapidly from feces to surrounding gas. Our aim was to quantify the fecal release of H2S and other volatiles (CO2, H2, CH4, methanethiol, and dimethylsulfide). METHODS: Fecal samples from 25 subjects with ulcerative colitis and 17 controls were incubated in 4-L containers, and gas release was assessed at intervals over 24 h. RESULTS: H2S release by ulcerative colitis feces was elevated 3-4-fold at every measurement point compared with normal feces (p < 0.003 at 24 h). The only other significant difference was increased CO2 release by ulcerative colitis feces at 1 h. Supplementation of fecal homogenates with sulfur-containing substrates showed that organic compounds (mucin, cysteine, taurocholate) provided more readily utilizable substrate for H2S production than did sulfate. CONCLUSIONS: Increased H2S release is a relatively localized metabolic aberration of ulcerative colitis feces. This increased H2S may reflect abnormalities of the fecal bacteria and/or substrate availability.

Adolescent↗
PubMed1997

Cardiac transplantation in New Zealand: eight years experience.

Between December 1987 and December 1995, 62 patients underwent orthotopic cardiac transplantation at Green Lane Hospital. Their cardiac dysfunction resulted from dilated cardiomyopathy (32), coronary artery disease (21), rheumatic heart disease (7), congenitally corrected transposition of the great arteries (1) and hypertrophic cardiomyopathy (1). Before transplantation all patients were in New York Heart Association (NYHA) functional class III or IV. Eight patients (13%) died in the perioperative period and a further seven (11%) died 1 to 4 years after transplantation. Actuarial 1 and 3 year survival was 87% and 80% respectively. Forty-five of forty-seven surviving patients were in NYHA functional class I at the time of analysis. The results confirm that cardiac transplantation has a limited but valuable role in the treatment of end stage myocardial dysfunction.

Actuarial Analysis↗
PubMed1996

Prospective evaluation of eligibility for thrombolytic therapy in acute myocardial infarction.

OBJECTIVES: To determine the proportion of patients presenting with acute myocardial infarction who are eligible for thrombolytic therapy. DESIGN: Cohort follow up study. SETTING: The four coronary care units in Auckland, New Zealand. SUBJECTS: All 3014 patients presenting to the units with suspected myocardial infarction in 1993. MAIN OUTCOME MEASURES: Eligibility for reperfusion with thrombolytic therapy (presentation within 12 hours of the onset of ischaemic chest pain with ST elevation > or = 2 mm in leads V1-V3, ST elevation > or = 1 mm in any other two contiguous leads, or new left bundle branch block); proportions of (a) patients eligible for reperfusion and (b) patients with contraindications to thrombolysis; death (including causes); definite myocardial infarction. RESULTS: 948 patients had definite myocardial infarction, 124 probable myocardial infarction, and nine ST elevation but no infarction; 1274 patients had unstable angina and 659 chest pain of other causes. Of patients with definite or probable myocardial infarction, 576 (53.3%) were eligible for reperfusion, 39 had definite contraindications to thrombolysis (risk of bleeding). Hence 49.7% of patients (537/1081) were eligible for thrombolysis and 43.5% (470) received this treatment. Hospital mortality among patients eligible for reperfusion was 11.7% (55/470 cases) among those who received thrombolysis and 17.0% (18/106) among those who did not. CONCLUSIONS: On current criteria about half of patients admitted to coronary care units with definite or probable myocardial infarction are eligible for thrombolytic therapy. Few eligible patients have definite contraindications to thrombolytic therapy. Mortality for all community admissions for myocardial infarction remains high.

Age Factors↗
PubMed1996

Fatal thrombocytopenia associated with Mycoplasma pneumoniae infection.

The case of a 21-year-old male who presented with pneumonia associated with thrombocytopenia and bleeding and who died from intracranial haemorrhage is described. Very high titres of complement fixing and agglutinating anti-mycoplasma antibodies indicated recent Mycoplasma pneumoniae infection. Possible links between thrombocytopenia and M. pneumoniae infection are discussed.

Adult↗
PubMed1996

Frequency of multiple Epstein-Barr virus infections in T-cell-immunocompromised individuals.

The Epstein-Barr virus (EBV) carrier state is characterized by latent infection of the general B-cell pool and by chronic virus replication at oropharyngeal sites. In Caucasian populations, most healthy carriers seem to harbor one dominant transforming virus strain, usually of type I rather than type 2, which persists over time and is detectable both in the blood and in the throat. This finding implies that once the virus carrier state is established, both viral reservoirs are largely if not completely protected from infection with additional strains. However, it is not known which facets of the immune response offer that protection. Here we address this question by a detailed study of EBV carriage in patients T-cell immunocompromised as a result of chronic human immunodeficiency virus (HIV) infection. Resident EBV strains were rescued from blood and from throat washings by using an in vitro transformation assay which aims to minimize bias toward faster-growing transformants; in this way, a mean of 16 independent isolations were made from each of 35 HIV-positive (predominantly male homosexual) patients. These virus isolates were characterized first at the DNA level by PCR amplification across type-specific polymorphisms in the EBNA2 and EBNA3C genes and across the 30-bp deletion and 33-bp repeat loci in the LMP1 gene and then at the protein level by immunoblotting for the strain-specific "EBNAprint" of EBNA1, -2, and -3C molecular weights. By these criteria, 18 of 35 patients harbored only one detectable EBV strain, usually of type 1, as do healthy carriers. However, the other 17 patients showed clear evidence of multiple infection with different EBV strains. In eight cases these strains were of the same type, again usually type 1, and were more often found coresident in throat washings than in the blood. By contrast, a further nine patients gave evidence of coinfection with type 1 and type 2 strains, and in these cases both virus types were detectable in the blood as well as in the throat. Immunological assays on these HIV-positive patients as a group showed a marked impairment of T-cell responses, reflected in reduced levels of EBV-specific cytotoxic T-cell memory, but an elevation of humoral responses, reflected in raised antibody titers to the EBV envelope glycoprotein gp340 and by the maintenance of virus neutralizing antibodies in serum. We infer that selective impairment of the T-cell system predisposes the host to infection with additional exogenously transmitted EBV strains.

AIDS-Related Opportunistic Infections↗
PubMed1996

Isolation of intertypic recombinants of Epstein-Barr virus from T-cell-immunocompromised individuals.

All wild-type isolates of Epstein-Barr virus (EBV) analyzed to date for allelic polymorphisms of the nuclear antigen EBNA2 gene (in the BamHI YH region of the genome) and of the EBNA3A,-3B, -3C genes (tandemly arranged in the BamHI E region) have proved either uniformly type 1 or uniformly type 2 at all four loci. The absence of detectable intertypic recombination in the wild probably reflects the rarity with which individual carriers, and certainly individual target cells, become coinfected with both virus types. Studying a group of human immunodeficiency virus-positive T-cell-immunocompromised patients known to be at enhanced risk of multiple EBV infections, we have isolated intertypic EBV recombinants from 2 of 40 patients analyzed. These recombinants, whose in vitro transforming capacity appeared at least equal to that of type 1 strains, carried a type 1 EBNA2 allele and type 2 EBNA3A,-3B, and -3C alleles. This was clearly demonstrable at the DNA level by PCR amplification using type-specific primer-probe combinations and was confirmed at the protein level (for EBNA2 and EBNA3C) by immunoblotting with type-specific antibodies. In one patient, the recombinant appeared to be the predominant strain, being the virus most commonly rescued by in vitro transformation both from the blood and from the throat washings on two separate occasions 20 months apart. A regular type 1 virus strain was also present in this individual, but this was not related to the recombinant since the two viruses carried type 1 EBNA2 genes with different patterns of variance from the B95.8 prototype sequence. In the other patient, recombinants were isolated on one occasion from the blood and on a separate occasion, 21 months later, from the throat; these recombinants were almost certainly related, being identical at several genomic polymorphisms and differing only in one facet of the "EBNAprint," the size of the EBNA1 protein. Three different type 1 viruses were also isolated from this patient, two of which carried EBNA2 genes with the same pattern of sequence variation from B95.8 as the recombinant; however, since this is a fairly common pattern of variance, the relationship of these viruses to the recombinant remains an open question. We infer that intertypic recombinants of EBV are not uncommon in HIV-positive T-cell-immunocompromised patients, that they arise in such individuals as a consequence of their increased frequency of mixed-type infections, and that they will prove capable of efficient transmission in the human population.

Amino Acid Sequence↗
PubMed1996

Thrombolytic therapy in the elderly. Pharmacoeconomic considerations.

Elderly patients have the highest absolute risk of death following an acute myocardial infarction (MI); 16.1% for those aged between 65 and 74 years, and 25.3% for those older than 75 years. Therefore, this age-group potentially may benefit most from the use of thrombolytic therapy. Cost-effectiveness analysis of streptokinase therapy has estimated that in patients aged 70 to 80 years, the cost per life-year saved is between $US21,200 and $US22,400 (1990 dollars) compared with placebo treatment. Additional mortality benefits have been shown for accelerated alteplase compared with streptokinase-treated patients (30-day mortality for alteplase and streptokinase was 6.3% and 7.3%, respectively; p = 0.001). A prospective cost-effectiveness study for all age groups concluded that the cost of an additional year of life saved with alteplase compared with streptokinase was $US32,678 (1993 dollars). This extra cost of alteplase treatment declined to $US13,410 and $US16,246 with patients older than 75 years with anterior and inferior MI, respectively. In patients aged 40 years or younger with an anterior or inferior MI, and for those aged up to 60 years with an inferior infarction, the accepted cost-effectiveness ratio of $US50,000 was exceeded. Alteplase appears to be a cost-effective therapy for the treatment of elderly patients with acute MI.

Aged↗
PubMed1995

Transoesophageal echocardiography in patients with prosthetic heart valves and systemic emboli: is it a useful investigation?

AIM: We aimed to assess the impact of transoesophageal echocardiography (TOE) on the clinical management of patients with prosthetic heart valves who had suffered from a systemic embolus. We wanted to know whether the TOE examination actually changed the management of these patients. METHODS: Prospective assessment of 38 TOE studies, with retrospective chart review of the hospital treatment. RESULTS: In 16 TOE studies, no potential cardiac source of emboli was found, however in 22 studies a cardiac abnormality was detected. As a result of the TOE, in 13 cases there was a definite change in clinical management for the patient. CONCLUSION: A TOE is an important examination for patients with a prosthetic valve who present with a systemic embolus.

Adult↗
PubMed1995

Good long-term outcome following surgical repair of post-infarction ventricular septal defect.

BACKGROUND: A post-infarction ventricular septal defect (VSD) is a serious complication of a myocardial infarction with 90% of patients dying by two months, in published series. Urgent surgical repair improves the prognosis. AIMS: To assess the Green Lane Hospital experience over a ten year period, especially with regard to hospital mortality and long-term follow up. METHODS: A retrospective case note review of all 35 consecutive patients undergoing post-infarct VSD repair from 1981 to 1990. Long-term follow up was obtained in all but one patient (97%). RESULTS: Twenty-one male and 14 female patients presented with a mean age of 67 years (range 51-75). All were in NYHA class 3 or 4, 14 (40%) were in cardiogenic shock. Following urgent surgical repair, 30 day mortality was 31% (11 patients). A further three patients died at two, 33 and 39 months; one patient was lost to follow up. At a mean follow up of 61 months (range 16-111), 15 patients were in NYHA class 1 or 2, five in NYHA class 3 or 4. For the whole group (n = 35) the actuarial survival was 66% at one year, 62% at three years and 58% at nine years. CONCLUSION: Post-infarct VSD surgery is of major prognostic benefit with patients obtaining a good long-term outcome.

Aged↗