Refining the risk-benefit equation for thrombolysis: How to identity the low risk patient before administering thrombolytic therapy

In view of the relative risk of intracranial haemorrhage and major bleeding with thrombolytic therapy, it is important ro identify as early as possible the low risk patient who may not have a net clinical benefit from thrombolysis in the setting of acute myocardial infarction. An analysis of 5434 hospital-treated patients with myocardial infarction in the Perth MONICA study showed that age below 60 and absence of previous infarction or diabetes, shock, pulmonary oedema, cardiac arrest and Q-wave or left bundle branch block on the initial ECG identified a large group of patients with a 28 day mortality of only 1%, and one year mortality of only 2%. Identification of baseline risk in this way helps refine the risk-benefit equation for thrombolytic therapy, and may help avoid unnecessary use of thrombolysis in those unlikely to benefit.

Magnetic resonance imaging and diseases of the liver and biliary tract. Part 2. Magnetic resonance cholangiography and angiography and conclusions

Magnetic resonance cholangiography (MRC) relies on the strong T-2 signal from stationary liquids, in this case bile, to generate images. No contrast agents are required, and the failure rate and risk of serious complications is lower than with endoscopic retrograde cholangiopancreatography (ERCP). Data from MRC can be summated to produce an image much like the cholangiogram obtained by using ERCP. In addition, MRC and conventional MRI can provide information about the biliary and other anatomy above and below a biliary obstruction. This provides information for therapeutic intervention that is probably most useful for hilar and intrahepatic biliary obstruction. Magnetic resonance cholangiography appears to be similar to ERCP with respect to sensitivity and specificity in detecting lesions causing biliary obstruction, and in the diagnosis of choledocholithiasis. It is also suited to the assessment of biliary anatomy (including the assessment of surgical bile-duct injuries) and intrahepatic biliary pathology. However, ERCP can be therapeutic as well as diagnostic, and MRC should be limited to situations where intervention is unlikely, where intrahepatic or hilar pathology is suspected, to delineate the biliary anatomy prior to other interventions, or after failed or inadequate ERCP. Magnetic resonance angiography (MRA) relies on the properties of flowing liquids to generate images. It is particularly suited to assessment of the hepatic vasculature and appears as good as conventional angiography. It has been shown to be useful in delineating vascular anatomy prior to liver transplantation or insertion of a transjugular intrahepatic portasystemic shunt. Magnetic resonance angiography may also be useful in predicting subsequent variceal haemorrhage in patients with oesophageal varices. (C) 2000 Blackwell Science Asia Pty Ltd.

Stressor categorization: acute physical and psychological stressors elicit distinctive recruitment patterns in the amygdala and in medullary noradrenergic cell groups

It has been hypothesized that the brain categorizes stressors and utilizes neural response pathways that vary in accordance with the assigned category. If this is true, stressors should elicit patterns of neuronal activation within the brain that are category-specific. Data from previous Immediate-early gene expression mapping studies have hinted that this is the case, but interstudy differences in methodology render conclusions tenuous. In the present study, immunolabelling for the expression of c-fos was used as a marker of neuronal activity elicited in the rat brain by haemorrhage, immune challenge, noise, restraint and forced swim. All stressors elicited c-fos expression in 25-30% of hypothalamic paraventricular nucleus corticotrophin-releasing-factor cells, suggesting that these stimuli were of comparable strength, at least with regard to their ability to activate the hypothalamic-pituitary-ad renal axis. In the amygdala, haemorrhage and immune challenge both elicited c-fos expression in a large number of neurons in the central nucleus of the amygdala, whereas noise, restraint and forced swim primarily elicited recruitment of cells within the medial nucleus of the amygdala. In the medulla, all stressors recruited similar numbers of noradrenergic (A1 and A2) and adrenergic (C1 and C2) cells. However, haemorrhage and immune challenge elicited c-fos expression In subpopulations of A1 and A2 noradrenergic cells that were significantly more rostral than those recruited by noise, restraint or forced swim. The present data support the suggestion that the brain recognizes at least two major categories of stressor, which we have referred to as 'physical' and 'psychological'. Moreover, the present data suggest that the neural activation footprint that is left in the brain by stressors can be used to determine the category to which they have been assigned by the brain.

Brain natriuretic peptide: Disease marker or more in cardiovascular medicine?

Brain natriuretic peptide (BNP) is predominantly a cardiac ventricular hormone that promotes natriuresis and diuresis, inhibits the renin-anglotensin-aldosterone axis, and is a vasodilator. Plasma BNP levels are raised in essential hypertension, and more so in left ventricular (LV) hypertrophy and heart failure. Plasma BNP levels are also elevated in ischemic heart disease. Attempts have been made to use plasma BNP levels as a marker of LV dysfunction, but these have shown that plasma BNP levels are probably not sensitive enough to replace echocardiography in the diagnosis of LV dysfunction. Pericardial BNP or N-BNP may be more suitable markers of LV dysfunction. Plasma BNP levels are also elevated in right ventricular dysfunction, pregnancy-induced hypertension, aortic stenosis, age, subarachnoid hemorrhage, cardiac allograft rejection and cavopulmonary connection, and BNP may have an important pathophysiological role in some or all of these conditions. Clinical trials have demonstrated the natriuretic, diuretic and vasodilator effects, as well as inhibitory effects on renin and aldosterone of infused synthetic human BNP (nesiritide) in healthy humans. BNP infusion improves LV function in patients with congestive heart failure via a vasodilating and a prominent natriuretic effect. BNP infusion is useful for the treatment of decompensated congestive heart failure requiring hospitalization. The clinical potential of BNP is limited as it is a peptide and requires infusion. Drugs that modify the effects of BNP are furthering our understanding of the pathophysiological role and clinical potential of BNP. Increasing the effects of BNP may be a useful therapeutic approach in heart failure involving LV dysfunction. The levels of plasma BNP are increased by blockers, cardiac glycosides and vasopeptidase inhibitors, and this may contribute to the usefulness of these agents in heart failure. (C) 2001 Prous Science. All rights reserved.

Alteplase: descendancy in myocardial infarction, ascendancy in stroke

Tissue type plasminogen activator is available, through recombinant technology, for thrombolytic use as alteplase. Alteplase is relatively clot specific and should cause less bleeding side effects than the non-specific agents such as streptokinase. Alteplase has been used successfully in evolving myocardial infarction (MI) to reopen occluded coronary arteries. It is probably equally effective or superior to streptokinase in opening arteries and reducing mortality in Mi. Alteplase is most effective when given early in Mi and is probably ineffective when given 12 h after the onset of symptoms. The effectiveness of alteplase in Mi can be increased by front loading with a bolus of 15 mg, followed by an infusion of 50 mg over 30 min and 35 mg over 60 min. Percutaneous transluminal coronary angioplasty or stenting is associated with a greater patency and lower rates of serious bleeding, recurrent ischaemia and death than alteplase in MI and is likely to take over from alteplase as the standard Mi treatment. A reduced dose of alteplase to increase coronary artery patency prior to angioplasty may be useful in Mi. An exciting new indication for the use of alteplase is in stroke, where it has become the first beneficial intervention. Alteplase is used to reopen occluded cerebral vessels but is associated with an increased risk of intracerebral haemorrhage. Alteplase is beneficial if given within 3 h of the onset of stroke but not after this time period. Therefore, the next challenge is to increase the percentage of people being diagnosed and treated within this period. Clinical trials have not established a role for alteplase in the treatment of acute coronary syndromes or deep vein thrombosis. However, alteplase is useful in treating pulmonary thromboembolism and peripheral vascular disease.

Management of orbitozygomatic fractures

Background: Management of orbitozygomatic fractures forms part of the scope of practice of many oral and maxillofacial Surgeons. As aspects of management vary among surgeons who treat such injuries, this confidential study was undertaken to examine some of the protocols of Australian and New Zealand oral and maxillofacial surgeons. Results: Eighty-one per cent of the respondents treated orbitozygomatic fractures and on average. each treated approximately 24 cases per year. Also, about one in five cases required orbital floor exploration. Further, the preferred imaging baseline was computed tomography plus plain X-rays. while the preferred implant materials for orbital floor reconstruction were autologous bone and resorbable membrane. The incidence of postoperative retrobulbar haemorrhage was estimated at approximately 1:1000. Conclusion: Most oral and maxillofacial surgeons treat orbitozygomatic injuries as part of their surgical scope.

Prevalence, severity, and heritability of Stephanofilaria lesions on cattle in central and southern Queensland, Australia

Observations of cattle in central and southern Queensland are collated to de. ne the prevalence and area of Stephanofilaria lesions associated with infestations of the buffalo fly, Haematobia irritans exigua. The observations were made on herds that were being used for other purposes. In a survey of similar to 1500 animals at Belmont in central Queensland in 1982, 98% of cows and 70% of calves had lesions. Most lesions were on the neck and dewlap and 10% were raw and weeping at the time of sampling. The total area of lesions per animal was strongly related to cattle breed and age. Old Bos taurus animals had the greatest area of lesions, whereas young Bos indicus had the least. Heritability estimates were low, averaging 0.01 for calves and 0.18 for cows. A smaller survey of cows and steers at Craighoyle in central Queensland in 1986 showed a higher numbers of lesions and positive correlations between the total lesion area and animal size. The lesion area increased with tick survival, suggesting that tick-resistant animals are also resistant to Stephanofilaria infection. Steers had smaller areas of lesions than cows, as found previously with cattle ticks. Long-term monitoring observations in central and southern Queensland between 1981 and 1986 showed that the total area of lesions was seasonal with a peak in late summer, consistent with the seasonal incidence of buffalo fly. Animals segregated into Low and High lesion herds maintained their differences over time. The lesions penetrated the dermis of the cattle hides and rendered the affected area unusable, but few lesions occurred on valuable parts of the hide so such economic effects are likely to be insignificant. One animal nearly died of a haemorrhage from a lesion on the dewlap and had to be treated. The results can inform policy on buffalo fly control, and biosecurity preparations in relation to the potential establishment of the OldWorld screw-worm fly, Chrysomyia bezziana, in Australia, which will be facilitated by the lesions. The results emphasise the significant animal welfare and biosecurity risks posed by the lesions in northern Australia.

The roles of exercise-induced immune system disturbances in the pathology of heat stroke - The dual pathway model of heat stroke

Heat stroke is a life-threatening condition that can be fatal if not appropriately managed. Although heat stroke has been recognised as a medical condition for centuries, a universally accepted definition of heat stroke is lacking and the pathology of heat stroke is not fully understood. Information derived from autopsy reports and the clinical presentation of patients with heat stroke indicates that hyperthermia, septicaemia, central nervous system impairment and cardiovascular failure play important roles in the pathology of heat stroke. The current models of heat stroke advocate that heat stroke is triggered by hyperthermia but is driven by endotoxaemia. Endotoxaemia triggers the systemic inflammatory response, which can lead to systemic coagulation and haemorrhage, necrosis, cell death and multi-organ failure. However, the current heat stroke models cannot fully explain the discrepancies in high core temperature (Tc) as a trigger of heat stroke within and between individuals. Research on the concept of critical Tc: as a limitation to endurance exercise implies that a high Tc may function as a signal to trigger the protective mechanisms against heat stroke. Athletes undergoing a period of intense training are subjected to a variety of immune and gastrointestinal (GI) disturbances. The immune disturbances include the suppression of immune cells and their functions, suppression of cell-mediated immunity, translocation of lipopolysaccharide (LPS), suppression of anti-LPS antibodies, increased macrophage activity due to muscle tissue damage, and increased concentration of circulating inflammatory and pyrogenic cytokines. Common symptoms of exercise-induced GI disturbances include diarrhoea, vomiting, gastrointestinal bleeding, and cramps, which may increase gut-related LPS translocation. This article discusses the current evidence that supports the argument that these exercise-induced immune and GI disturbances may contribute to the development of endotoxaemia and heat stroke. When endotoxaemia can be tolerated or prevented, continuing exercise and heat exposure will elevate Tc to a higher level (> 42 degrees C), where heat stroke may occur through the direct thermal effects of heat on organ tissues and cells. We also discuss the evidence suggesting that heat stroke may occur through endotoxaemia (heat sepsis), the primary pathway of heat stroke, or hyperthermia, the secondary pathway of heat stroke. The existence of these two pathways of heat stroke and the contribution of exercise-induced immune and GI disturbances in the primary pathway of heat stroke are illustrated in the dual pathway model of heat stroke. This model of heat stroke suggests that prolonged intense exercise suppresses anti-LPS mechanisms, and promotes inflammatory and pyrogenic activities in the pathway of heat stroke.

Choroidal osteoma: evidence of progression and decalcification over 20 years

Choroidal osteoma is a rare, benign, ossifying tumour of the choroid of unknown aetiology. In contrast to other types of intraocular ossification, choroidal osteoma is found typically in young healthy females in the second or third decades of life with no history of systemic or ocular disease. Choroidal osteoma is a deep, pale yellow lesion with distinct geographic borders at the juxtapapillary or macular region, with branching 'spider' vessels on the surface of the tumour. These features should help differentiate choroidal osteoma from other types of intraocular tumour and the diagnosis can be confirmed with ultrasonography and computerised tomography. Here we report an initially unilateral case of choroidal osteoma, which decalcified over 20 years but during the same period the fellow eye also developed a choroidal osteoma to become a bilateral case. Despite the benign nature of the tumour, vision may be compromised by gradual atrophy of the overlying retina, serous retinal detachment, accumulation of sub-retinal fluid and sub-retinal haemorrhage associated with choroidal neovascularisation. Frequent examinations are recommended for patients with choroidal osteoma, for early detection of a subretinal neovascular membrane and potential treatment with laser photocoagulation.

The use of recombinant activated factor VII for refractory bleeding post complex cardiothoracic surgery

We reviewed the outcome following use of recombinant activated factor VII (rVIIa) in patients with major bleeding post cardiothoracic surgery in our unit between January 2002 and July 2004. The unit consists of 16 cardiothoracic intensive care beds in a public metropolitan teaching hospital which serves as a referral centre for heart and lung transplant surgery Patients with refactory bleeding following cardiothoracic surgical procedures who were treated with rVIIa were identified. A total of 12 episodes of rVIIa use were recorded in ten patients, including three episodes with ventricular assist devices, and 5 heart and/or lung transplants. The median dose used was 85 mu g/kg. Chest tube drainage decreased in all patients following administration of rVIIa; median chest tube drainage decreased front 445 ml/h to 171 ml/h (P=0.03). Despite cessation of bleeding, mortality was high, when rVIIa was used after more than 24 hours. In six episodes, despite early rVIIa use (within six hours), continued bleeding necessitated return to theatre, where a surgical source of bleeding was found. In this small retrospective study, rVIIa significantly reduced bleeding that was refractory to standard blood product transfusion. In this series of patients., those that did not respond to rVIla early in the postoperative phase were found to have a surgical source of bleeding.

Maternal health during pregnancy and perinatal mortality in Bangladesh: evidence form a large-scale community-based clinical trial

Perinatal mortality is very high in Bangladesh. In this setting, few community-level studies have assessed the influence of underlying maternal health factors on perinatal outcomes. We used the data from a community-based clinical controlled trial conducted between 1994 and 1997 in the catchment areas of a large MCH/FP hospital located in Mirpur, a suburban area of Dhaka in Bangladesh, to investigate the levels of perinatal mortality and its associated maternal health factors during pregnancy. A total of 2007 women were followed after recruitment up to delivery, maternal death, or until they dropped out of the study. Of these, 1584 who gave birth formed our study subjects. The stillbirth rate was 39.1 per 1000 births [95% confidence interval (CI) 39.0, 39.3] and the perinatal mortality rate (up to 3 days) was 54.3 per 1000 births [95% CI 54.0, 54.6] among the study population. In the fully adjusted logistic regression model, the risk of perinatal mortality was as high as 2.7 times [95% CI 1.5, 4.9] more likely for women with hypertensive disorders, 5.0 times [95% CI 2.3, 10.8] as high for women who had antepartum haemorrhage and 2.6 times [95% CI 1.2, 5.8] as high for women who had higher haemoglobin levels in pregnancy when compared with their counterparts. The inclusion of potential confounding variables such as poor obstetric history, sociodemographic characteristics and preterm delivery influenced only marginally the net effect of important maternal health factors associated with perinatal mortality. Perinatal mortality in the study setting was significantly associated with poor maternal health conditions during pregnancy. The results of this study point towards the urgent need for monitoring complications in high-risk pregnancies, calling for the specific components of the safe motherhood programme interventions that are designed to manage these complications of pregnancy.

Drug utilization evaluation of parenteral proton pump inhibitors

Current evidence supports parenteral infusion of proton pump inhibitors (PPI) after endoscopic treatment of bleeding peptic ulcers and such treatment seems reasonable where there is active bleeding or visible vessel on endoscopy. Parenteral boluses of PPI can be used in patients nil by mouth who cannot tolerate oral therapy. We sought to examine the appropriateness of parenteral PPI use. Drug utilisation evaluation was performed on 94 patients admitted to a 500 bed metropolitan hospital. 39 patients received continuous parenteral infusion of omeprazole (8 mg/ h) over a mean of 60 ± 29 h. 55 patients had parenteral boluses (40 mg bd) of omeprazole over a mean of 5 ± 4 days. Indications for PPI infusion (n = 39) were: major haemorrhage requiring transfusion (23), minor haemorrhage (8), dyspepsia (4) and others (4). 31 of the 39 patients on PPI infusion had upper gastrointestinal (GI) endoscopy. PPI infusion was commenced prior to endoscopy in 26 (84%) patients. 13 patients (33%) had active bleeding or visible non bleeding vessels at endoscopy. Only 11 patients (28%) had endoscopically treated peptic ulcers. Indications for parenteral PPI boluses (n = 55) included patients nil by mouth unable to take maintenance PPI orally (21), minor haemorrhage (8), peptic ulcer prophylaxis in seriously unwell (6), major haemorrhage (4), dyspepsia (2), postoprative period following peptic ulcer surgery (2) and others (12). Endoscopy was performed in 10 patients (18%) with only 1 endoscopically treated peptic ulcer. Our data suggest significant inappropriate use of parenteral PPI, which may be used for minor GI bleeding and dyspepsia and are typically commenced prior to endoscopy. These findings can explain the costly hospital expenditure on PPI.