Diagnosing Paroxysmal Atrial Fibrillation: Are Biomarkers the Solution to This Elusive Arrhythmia?

Atrial fibrillation (AF) is the commonest sustained arrhythmia globally and results in significantly increased morbidity and mortality including a fivefold risk of stroke. Paroxysmal atrial fibrillation (PAF) constitutes approximately half of all AF cases and is thought to represent an early stage of the disease. This intermittent form of atrial arrhythmia can be a challenge to identify and as a result many affected individuals are not prescribed appropriate antithrombotic therapy and hence are at risk of stroke and thromboembolism. Despite these adverse outcomes there have been relatively few diagnostic advances in the field since the introduction of the Holter monitor in 1949. This review aims to establish the available evidence for electrophysiological, molecular, and morphological biomarkers to improve the detection of PAF with reference to the underlying mechanisms for the condition.

Waterhouse-Friderichsen syndrome after infection with group A streptococcus.

We report a case of Waterhouse-Friderichsen syndrome associated with group A streptococcus (GAS) toxic shock syndrome in a previously healthy man. The patient presented with neck pain and fevers of 2 days' duration. Computed tomography of the neck revealed a mass in the retropharyngeal space, suggesting an abscess. Despite prompt treatment with appropriate antibiotics, the patient experienced a fulminant course and died within 8 hours of presentation. Antemortem blood cultures grew GAS positive for exotoxins A, B, and C. Postmortem examination revealed bilateral adrenal hemorrhage, consistent with Waterhouse-Friderichsen syndrome. Immunohistochemical analysis of the adrenal glands revealed the presence of GAS antigens. However, no disseminated intravascular coagulation was evident. This case demonstrates that adrenal hemorrhage can occur without associated coagulopathy and may result directly from the action of bacterial toxins.

A general software package for the handling of medical images.

PICS (portable imaging computer software), is a software system designed for handling and processing a variety of types of medical image. It has been designed to satisfy the following criteria: (a) the software should be portable between different items of hardware with minimal alteration; (b) there should be a simple operator interface to enable use by inexperienced users, while avoiding the need for experienced users to be directed through tedious menu trees; (c) the programming environment should enable simple integration of new data handling protocols. To meet these requirements the software was written in FORTRAN using structured subroutine organization. The software has basic image handling and processing facilities and contains a comprehensive set of nuclear medicine clinical protocols. Other facilities include alignment of images from different modalities with display of superimposed images and ability to handle, analyse and display three-dimensional data sets. Data transfer programs have been written to capture data from gamma camera, CT, MRI, ultrasound and radiographs by converting the images to a common data format. The system provides a hospital with a central digital image handling resource, enabling investigation of the value of digital image processing in potential clinical applications.

Continuous 24 hour ambulatory monitoring of intragastric pH in man.

A system has been developed which permits continuous 24 hour ambulatory recording of intragastric pH under near-physiological conditions. The system utilises a Cecar combination pH electrode connected through a pre-amplifier to an Oxford Medical Systems Medilog 4-24 cassette recorder, and the pH recorded continuously on to tape. The data is replayed at high speed, digitised and then analysed. Sources of error included system drift, system noise and the effect of changes in electrode environment due to saliva, food, loss of fluid contact, temperature variations and electrode time constant. These were found to be small. In contrast, the major changes in pH detected reflect real changes at the electrode tip. These changes can be recorded by the system. Developments in electronics and improvements in both the size and quality of pH electrodes, over the past few decades, has enabled intragastric pH recordings to be made with greater ease. However, a large number of investigators still assess gastric acidity by infrequent, intermittent sampling of gastric secretion through a naso-gastric tube. This new ambulatory system is a significant improvement and its versatility allows studies in acid secretion physiology, pharmacology and pathophysiology.

A comparison between the use of a shadow shield whole body counter and an uncollimated gamma camera ain the assessment of the seven-day retention of SeHCAT.

We have compared the 7-day retention of the radioisotope bile salt analogue SeHCAT (75Se-23-selena-25-homotaurocholate), by whole body counting and by uncollimated gamma camera measurement, in phantoms and in 25 patients with inflammatory bowel disease. The results correlate with a linear correlation coefficient of 0.96. An uncollimated gamma camera can be used to assess bile acid malabsorption when a whole body radioactivity monitor is not available.

The effect on paracetamol absorption of stimulation and blockade of beta-adrenoceptors.

1 The effect of drugs acting on beta-adrenoceptors on the absorption and excretion of paracetamol was studied in 26 volunteers and nine patients with mild hypertension, each subject acting as his/her own control. 2 Isoprenaline given 30 min before paracetamol significantly slowed absorption, the effect being dose related, and blocked by prior administration of propranolol. 3 When isoprenaline was given immediately before the paracetamol, absorption was not altered, although a cardiovascular response was seen. 4 Oral salbutamol also delayed paracetamol absorption. 5 Propranolol given alone increased the rate of paracetamol absorption. 6 These results with the changes in the rate of gastric emptying produced by these agents.

The effect of beta-adrenoceptor agonists and antagonists on gastric emptying in man.

1. The effect of beta-adrenoceptor agonists and antagonists on gastric emptying of a solid meal labelled with Indium113m was measured by a gamma camera in healthy volunteers or patients with hypertension. Each subject acted as his own control. 2 In ten subjects given isoprenaline (10 or 20 mg) sublingually 30 min before the meal, gastric emptying half-times were significantly prolonged (P less than 0.05). No effect was observed when isoprenaline was given immediately before the meal. 3 Salbutamol, 4 mg four times daily for 1 week also significantly prolonged gastric emptying in four subjects (P less than 0.05). 4 The effect of isoprenaline on gastric emptying was blocked by propranolol 40 mg four times daily for 1 week. 5 In ten subjects propranolol 40 mg four times daily alone for 1 week was found to significantly speed up gastric emptying (P less than 0.005), suggesting that emptying of the normal stomach is subject to some degree of adrenergic inhibition.

Gastric emptying in control subjects and patients with duodenal ulcer before and after vagotomy.

The emptying of a solid meal labelled with Indium 113mDTPA from the stomach was studied with a gamma camera in 26 normal subjects, 27 patients with duodenal ulcer, on 41 occasions after truncal vagotomy and pyloroplasty and 38 times after highly selective vagotomy. Applying the method of principal component analysis to the results, differences were detected between control and duodenal ulcer subjects and two probable subgroups of duodenal ulcer were observed. Half emptying times did not reveal these patterns. After vagotomy, delayed emptying was general at one week. At one month, patients after highly selective vagotomy had a more normal result than those with truncal vagotomy and pyloroplasty (TV), but by six months no significant difference in overall emptying rate was found, although changes in the pattern of gastric emptying persisted in some patients after TV.

Discriminant value of thyroid function tests.

Different thyroid function tests permitted a final classification of 204 consecutive patients with suspected thyroid disorders into three populations (thyrotoxic, euthyroid, and hypothyroid). Linear discriminant analysis was applied to all test results (10 variates) on adjacent population pairs. Two invitro tests (serum protein bound iodine (P.B.I.) and tri-iodothyronine (T-3) uptake values) gave good separation of thyrotoxic from euthyroid patients and fairly good distinction of hypothyroid patients. If a (131)I uptake figure was then added to the in-vitro results most patients (95.5%), including thse initially classified as equivocal, were correctly diagnosed. Other tests, including clinical questionnaires, were poor discriminants.Two new techniques of utilizing the test data were devised. Firstly, the data from the two in-vitro tests were also displayed graphically, and oblique boundary lines derived from the discriminant functions gave better separation of patients than previously used limits or mathematical expressions of "free thyroxine." Secondly, a nomogram incorporating the best four discriminants was designed as a diagnostic aid and proved to be the best means of interpreting the tests.Discriminant analysis of this kind can be used in the interpretation of diagnostic tests in any branch of medicine, and it allows the best use to be made of the available data.