Genetic markers of repolarization and arrhythmic events after acute coronary syndromes.

BACKGROUND: There is a genetic contribution to the risk of ventricular arrhythmias in survivors of acute coronary syndromes (ACS). We wished to explore the role of 33 candidate single nucleotide polymorphisms (SNPs) in prolonged repolarization and sudden death in patients surviving ACS. METHODS: A total of 2,139 patients (1680 white ethnicity) surviving an admission for ACS were enrolled in the prospective Coronary Disease Cohort Study. Extensive clinical, echocardiographic, and neurohormonal data were collected for 12 months, and clinical events were recorded for a median of 5 years. Each SNP was assessed for association with sudden cardiac death (SCD)/cardiac arrest (CA) and prolonged repolarization at 3 time-points: index admission, 1 month, and 12 months postdischarge. RESULTS: One hundred six SCD/CA events occurred during follow-up (6.3%). Three SNPs from 3 genes (rs17779747 [KCNJ2], rs876188 [C14orf64], rs3864180 [GPC5]) were significantly associated with SCD/CA in multivariable models (after correction for multiple testing); the minor allele of rs17779747 with a decreased risk (hazard ratio [HR] 0.68 per copy of the minor allele, 95% CI 0.50-0.92, P = .012), and rs876188 and rs386418 with an increased risk (HR 1.52 [95% CI 1.10-2.09, P = .011] and HR 1.34 [95% CI 1.04-1.82, P = .023], respectively). At 12 months postdischarge, rs10494366 and rs12143842 (NOS1AP) were significant predictors of prolonged repolarization (HR 1.32 [95% CI 1.04-1.67, P = .022] and HR 1.30 [95% CI 1.01-1.66, P = .038], respectively), but not at earlier time-points. CONCLUSION: Three SNPs were associated with SCD/CA. Repolarization time was associated with variation in the NOS1AP gene. This study demonstrates a possible role for SNPs in risk stratification for arrhythmic events after ACS.

Military tropical medicine.

Tropical diseases remain a significant threat to deployed military personnel as demonstrated by recent outbreaks amongst troops in Sierra Leone, Iraq and Afghanistan. Five cases are presented from military deployments in tropical or sub-tropical areas, which illustrate important diseases and diagnostic principles for military physicians.

OakEcol: A database of Oak-associated biodiversity within the UK.

Globally there is increasing concern about the decline in the health of oak Quercus trees. The impact of a decline in oak trees on associated biodiversity, species that utilize oak trees, is unknown. Here we collate a database of all known birds, bryophytes, fungi, invertebrates, lichens and mammals that use oak (Quercus petraea and Q. robur) in the UK. In total 2300 species are listed in the database. For each species we provide a level of association with oak, ranging from obligate (only found on oak) to cosmopolitan (found on a wide range of other tree species). Data on the ecology of each oak associated species was collated: part of tree used, use made of tree (feeding, roosting, breeding), age of tree, woodland type, tree form (coppice, pollarded, or natural growth form) and season when the tree was used. Data on use or otherwise by each of the 2300 species of 30 other tree species was also collated. A complete list of data sources is provided. For further insights into how this data can be used see Collapsing foundations: The ecology of the British oak, implications of its decline and mitigation options [1]. Data can be found at EIDC https://doi.org/10.5285/22b3d41e-7c35-4c51-9e55-0f47bb845202.

Patients with acute myocardial infarction have an inaccurate understanding of their risk of a future cardiac event.

BACKGROUND: Accurate perceptions of future cardiac risk are important to ensure informed treatment choices and lifestyle adaptation in patients following myocardial infarction (MI). The aim of this study was to investigate whether risk perceptions of patients with MI were accurate compared with an established clinical risk model. METHODS: Seventy-nine consecutive patients with acute MI admitted to the Coronary Care Unit, Auckland Hospital, completed a questionnaire assessing risk perceptions. Clinical data were used to calculate patients' Thrombolysis In Myocardial Infarction (TIMI) risk scores, a validated predictive model of prognosis. The main outcome measures were the associations between perceived risk, TIMI risk scores and troponin T. RESULTS: Patients' risk perceptions showed no correlation with thrombolysis in myocardial infarction risk scores (r = -0.06; P = 0.61) or with troponin T (r = -0.07; P = 0.53). Patients' risk perceptions were not significantly associated with age or sex, and were not significantly higher in those who had experienced a previous MI, a family history of coronary heart disease, diabetes or smokers. Higher perceived risk was significantly associated with a number of illness perceptions, including worse consequences of the MI and lower beliefs in the benefit of treatment. Patients who overestimated their risk were more anxious than other patients (F(2, 73) = 22.97; P = 0.0001). CONCLUSION: Patients with MI ideas about their personal risk of future MI are not congruent with their clinical risk assessments. Inpatient hospital care appears to be unsuccessful in communicating prognosis effectively to patients. Improving the accuracy of risk perceptions may help decrease unnecessary cardiac anxiety and invalidism in some patients and prompt risk-reducing behaviours in others.

Relationship between corrected TIMI frame counts at three weeks and late survival after myocardial infarction.

OBJECTIVES: To evaluate the corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (CTFC) as a predictor of late survival after myocardial infarction. BACKGROUND: Thrombolysis in Myocardial Infarction flow grades predict late survival after myocardial infarction. The CTFC provides a more reproducible measurement of infarct-related artery blood flow than the TIMI flow grade, and has been linked to 30-day outcomes, but it has not yet been established how the CTFC correlates with late survival. METHODS: Of 1,001 patients with acute myocardial infarction presenting within 4 h of symptom onset, 882 underwent angiography at approximately three weeks. Infarct artery flow was assessed, blinded to clinical outcomes, according to the CTFC and TIMI flow grade. Late cardiac mortality and survival were determined in 97.5% of patients. RESULTS: The mean CTFC was 40 +/- 29 in 644 patent infarct arteries (median, 34 [interquartile range, 24 to 47]). The CTFC, assessed as a continuous univariate variable, was found to be a predictor of five-year survival, as was the TIMI flow grade (both p < 0.001). On multivariate analysis, factors associated with five-year survival included the ejection fraction or end-systolic volume index (both p < 0.001); exercise duration (p = 0.005), age (p = 0.008), diabetes (p = 0.02) and CTFC (p = 0.02) or TIMI flow (p = 0.02). The same factors, except for the CTFC and TIMI flow grade, were predictors of 10-year survival. CONCLUSIONS: The CTFC three weeks after myocardial infarction was an independent predictor of five-year survival, but not 10-year survival. Although the CTFC provided additional prognostic information within TIMI flow grades, its superiority was not demonstrated.

Abnormal coronary flow in infarct arteries 1 year after myocardial infarction is predicted at 4 weeks by corrected Thrombolysis in Myocardial Infarction (TIMI) frame count and stenosis severity.

Because 24% to 30% of patent infarct-related arteries occlude in the year following thrombolytic therapy for acute myocardial infarction, angiographic factors including corrected Thrombolysis in Myocardial Infarction (TIMI) frame count which may predict abnormal infarct-artery flow, require definition. We examined changes in coronary flow and infarct-artery lesion severity by computerized quantitative angiography over 1 year in 154 patients with a patent infarct-related artery 4 weeks after myocardial infarction. These patients were randomized to receive either ongoing daily therapy of 50 mg aspirin and 400 mg dipyridamole, or placebo. All angiograms were interpreted blind in our core angiographic laboratory. Infarct-artery flow, assessed by corrected TIMI frame counts, was normal (< or = 27) in 46% and 45% of patients at 4 weeks and 1 year, respectively. At 4 weeks, patients with corrected TIMI frame counts < or = 27 had higher ejection fractions (60+/-11% vs 56+/-12%; p = 0.04) than those with corrected TIMI frame counts >27. On multivariate analysis, corrected TIMI frame count and stenosis severity were predictive of late abnormal infarct-artery flow (TIMI 0 to 2 flow, both p <0.01). Only stenosis severity at 4 weeks predicted reocclusion at 1 year (p <0.0001). Aspirin and dipyridamole had no effect on flow or reocclusion. Thus, corrected TIMI frame count and stenosis severity at 4 weeks was highly correlated with infarct-artery flow at 1 year.

Results of percutaneous coronary angioplasty in patients <40 years of age.

This study examined factors influencing the outcome of percutaneous transluminal coronary angioplasty (PTCA) in patients <40 years of age. We followed 86 patients (mean age 37 years) treated from 1982 to 1994. The primary procedural success was 90%. At follow-up of 83 patients (97%) at a mean of 48 +/- 33 months (range 5 to 147), there had been 3 late deaths. Actuarial survival at 5 and 10 years was 95% and 91%, respectively. At review only 5% of patients had class III angina and no patient had class IV angina. Repeat revascularization (PTCA alone in 21 [25%], surgery in 8 [10%], or both in 10 [12%] patients) was performed for restenosis in 29 patients (35%) and for disease progression at other sites in 10 patients (12%). On multivariate analysis, a history of diabetes mellitus (p <0.02) was the only factor associated with death or a subsequent cardiovascular event (myocardial infarction, stroke, or hospital admission with unstable angina). At follow-up, 20 patients (24%) still smoked, 64 (77%) had a total cholesterol level > or = 200 mg/dl, 20 (24%) had a body mass index > or = 30, and 15 (18%) were not taking aspirin. In conclusion, PTCA in adults <40 years of age has excellent early results with a low morbidity and mortality. The medium-term prognosis and control of symptoms was good, although by 5 years, further revascularization was required in almost half of the patients.

Review article: antibiotics and the gut.

Antibiotics have an important place in the management of gastrointestinal disease. Recent studies have demonstrated efficacy in acute bacterial gastroenteritis caused by salmonellae and campylobacteriaceae, shigellae and enterotoxigenic strains of E coli (ETEC). Tetracycline remains effective in cholera. Antibiotic resistance is widespread amongst the enteric pathogens and can quickly spread during epidemics of infective diarrhoeas. It is important that antibiotics are reserved for the treatment of serious infections lest their effectiveness in these conditions be lost. Campylobacter pylori appears to be an important cause of chronic active gastritis and is amenable to treatment with antibiotics and bismuth salts. The role of C. pylori in the pathogenesis of peptic ulcer disease is not yet established but there is mounting evidence that antibiotic treatment will have a place in the treatment of this common condition. The effect of antibiotics on the normal intestinal microflora can have serious consequences. It is a major cause of resistance in urinary tract pathogens, can result in outbreaks of hospital infection with resistant organisms and frequently results in C. difficile associated diarrhoea.

Temperature dependence of macroamylase binding.

The presence of macroamylasemia can be suspected when a patient has low renal clearance of amylase relative to creatinine (Cam/Ccr). However, the Cam/Ccr is seldom reduced to the extent expected given the fraction of amylase that appears to be bound in the macroamylase complex by gel filtration studies at 3 degrees C. Therefore, we tested the possibility that the binding of amylase in macroamylase complexes was temperature dependent and that binding at physiological temperatures might be less than at 3 degrees C. Gel filtration of five macroamylase-containing sera was carried out at temperatures of 3 degrees, 25 degrees, 37 degrees, 43 degrees, and 49 degrees C. Binding of amylase in the complex decreased as the temperature increased with virtually all amylase bound at 3 degrees C and virtually no amylase bound at 49 degrees C. The fraction of the amylase that bound at 37 degrees C was approximately what would have been predicted from the Cam/Ccr of each of the five subjects. We conclude that amylase binding in macroamylase complexes is extremely temperature sensitive and appreciable changes in binding may occur over the physiological temperature range of 37-41 degrees C.

Seasonality of presentation of imported Plasmodium vivax malaria in Birmingham, UK.

Residents of the UK returning from northern Pakistan with Plasmodium vivax infection tend to develop symptoms and present to hospital in the summer months, irrespective of the month of return. Thus, infections acquired in the cooler months of November to April appear to have a longer latency before presentation. Experiments suggest that more hypnozoites arise from the liver when ambient temperatures fall, somehow 'programming' parasites within biting mosquitoes.

Exchange transfusion in severe falciparum malaria.

Three cases of severe falciparum malaria with high parasitaemia, one of them complicated by disseminated intravascular coagulation, were treated with exchange transfusion in addition to conventional chemotherapy. All three made a good recovery. There are few previous reports of this treatment which deserves wider attention and further assessment.

The pupillary light reflex in normal subjects.

In 19 normal subjects the pupillary reflex to light was studied over a range of stimulus intensities by infrared electronic pupillography and analysed by a computer technique. Increasing stimulus intensity was associated with an increase in direct light reflex amplitude and maximum rate of constriction and redilatation. Latency from stimulus to onset of response-decreased with increasing stimulus intensity. The normal range for each of these parameters is given and the significance of these results in clinical pupillary assessment discussed.

Electrophysiological signs of retinal dopamine deficiency in recently diagnosed Parkinson's disease and a follow up study.

Electrophysiological studies, including electrooculogram (EOG), and simultaneously recorded flash and pattern evoked electroretinograms (FERG and PERG) and visually evoked potentials (FVEP and PVEP) were made in 1988 on 10 newly diagnosed untreated Parkinson's patients at Stage 1 of the Hoehn and Yahr scale. Follow up studies were made on five out of the 10 patients when their disease had progressed to Stage 2 during 1993. The earliest and only sign of abnormality detected in the Stage 1 of Parkinson's patients in 1988 was a delay in the time to reach the peak light rise in the EOG. When the disease had progressed to Stage 2, not only a delay in the time to reach the peak light rise but also a reduction in the amplitude of the peak light rise in the EOG, together with changes in PERG, FERG and PVEPs were demonstrable. These changes observed in PERG, FERG and PVEPs were generally consistent with those reported by previous studies. It is suggested that the reason for the susceptibility of pigment epithelial function to dopamine deficiency in Parkinson's disease may be due to the pigment epithelium being at the extremity of the diffusion pathway from dopamine release sites at the inner plexiform layer.

Inequality of the direct and consensual light reflexes in normal subjects.

Anisocoria in darkness and during reflex responses to unilateral light stimulation was studied in 150 normal subjects with television pupillometry. It was commonly found that the direct light reaction of the stimulation eye exceeded the consensual reaction of the other eye. This light-induced anisocoria, termed 'contraction anisocoria', had a mean value of 0.075 mm or 6.1 % of light reflex amplitude. The measurement showed a high degree of repeatability in 20 subjects who were tested on two occasions a year apart. It occurred in the presence and absence of prior dark adaptation and increased proportionally with reflex amplitude as the intensity of the stimulating light was raised. IT IS CONCLUDED THAT, CONTRARY TO PREVIOUS OPINION, A SMALL DEGREE OF CONTRACTION ANISOCORIA IS NORMAL.

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.

Imaging of cardiac metastatic melanoma: trans-oesophageal echocardiography or magnetic resonance imaging?

Two cases of isolated cardiac metastatic melanoma are described. Images from the first case using magnetic resonance scanning were complimented by the clearer images obtained with trans-oesophageal echocardiography in the second case. Trans-oesophageal echocardiography may be the technique of choice to image intra-cardiac metastatic tumours.

Spontaneous coronary artery dissection in a young woman resulting from an intense gymnasium "work-out".

We report on a young housewife who developed a spontaneous coronary artery dissection following unusually severe exercise. She survived an extensive anterior myocardial infarction with the help of an emergency coronary artery vein graft. This rare diagnosis must be considered when a young woman presents with an acute myocardial infarction.

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.

Management of patients with unstable angina in a general cardiology unit.

AIMS: To review the clinical management of patients with unstable angina and to relate prospectively initial risk stratification, according to the Braunwald criteria, to subsequent cardiovascular events. METHODS: From February to April 1996 we performed a three month prospective review of all patients with a diagnosis of unstable angina admitted to the coronary care unit at Auckland Hospital. RESULTS: One hundred and four patients (61% male), with a mean age of 64 years, were classified as high (58%), intermediate (41%) or low risk (1%) for an adverse cardiac event. Twelve (12%) patients had a documented myocardial infarction, of whom 11 were in the high-risk group (p = 0.038). During hospitalisation there was one death. Twelve (12%) patients underwent inpatient exercise testing, five of whom proceeded to a coronary angiogram prior to hospital discharge. Twenty-two (21%) unstable patients underwent inpatient angiography without prior exercise testing. Twenty-one (20%) patients required revascularisation on the same admission: percutaneous coronary angioplasty (n = 14) or coronary artery bypass grafting (n = 7). Twelve of these 21 patients were in the high-risk group (p = 0.999, NS). CONCLUSION: Patients admitted with unstable angina had low inpatient mortality but a 12% rate of subsequent myocardial infarction. Braunwald low-risk unstable angina patients were not admitted to the coronary care unit. Braunwald high-risk patients were more likely to develop a subsequent myocardial infarction. Stratification of patients into intermediate or high-risk groups did not relate to initial medical management or subsequent revascularisation. Thus, while this method of risk stratification may predict cardiovascular events, it may be of limited clinical use in the New Zealand environment.

An audit of phase II cardiac rehabilitation at Auckland hospital.

AIM: To audit Phase II cardiac rehabilitation services available to patients admitted to Auckland Hospital in order to assess patient uptake and to identify problems with patient recruitment to the service. METHODS: We performed a retrospective review from 1/8/ 97 to 30/9/97 of all patients admitted to the coronary care/ cardiology departments in Auckland Hospital. RESULTS: There were 289 patient admissions in this two month period, of which 22 (8%) were readmissions. 154 (54%) were admissions with provisional diagnoses of chest pain, of whom eight were readmissions. A total of 113 (39%) patients were felt to be suitable for the rehabilitation programme, of whom 50 (44%) attended one or more sessions and 22 (19%) completed the six week programme. 63 (56%) of the eligible patients did not attend any session. Reasons for non-attendance included the distance to be travelled, availability of transport and problems associated with taking time off work. A major finding of the audit was that the systems currently in place to follow patients are inadequate to allow formal audit and evaluation of the rehabilitation service. CONCLUSIONS: Although a reasonable rehabilitation service exists for Auckland Hospital patients, less than half of suitable patients attend a single session. There is a need for better collection and recording of patient data in order to facilitate the development of evaluation and audit tools.