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W S Waring

Publications and source records attributed to W S Waring.

At least 19 recordsLinked to original sources

Redefining the ACE-inhibitor dose-response relationship: substantial blood pressure lowering after massive doses.

OBJECTIVES: The blood pressure-lowering dose-response relationship for angiotensin converting enzyme (ACE) inhibitors is assumed to flatten at doses higher than those conventionally used in clinical practice. However, existing clinical trial data do not adequately address the haemodynamic effects of high ACE inhibitor dosages. Therefore, we examined the blood pressure responses in patients presenting to hospital following a deliberate ACE inhibitor overdose. METHODS: The study design was a retrospective case review, and included all patients who presented to our hospital in the past 5 years after an ACE inhibitor overdose. The data collected were heart rate and systemic blood pressure at various times after ingestion and maximum haemodynamic derangement; these were compared to baseline or recovered values. RESULTS: Data from 33 patients (24 men) were evaluated. The median (inter-quartile range, IQR) age of the patients was 49 years (IQR: 42-56 years). The median stated dose ingested was 140 mg (IQR: 60-280 mg), which is 20x (IQR: 7-42) the defined daily dose. The maximum fall in systolic blood pressure was 50 mmHg (IQR: 40-64 mmHg), diastolic blood pressure was 35 mmHg (IQR: 26-43 mmHg) and mean blood pressure was 39 mmHg (IQR: 30-47 mmHg). CONCLUSIONS: The observed reduction in blood pressure following an overdose of an ACE inhibitor was greater than anticipated based on data from therapeutic doses. We conclude that a blood pressure-lowering dose-response relationship extends to higher ACE inhibitor doses than those conventionally used in clinical practice.

Adrenergic beta-Antagonists↗

Rapid onset of haemodynamic effects after angiotensin converting enzyme-inhibitor overdose: implications for initial patient triage.

BACKGROUND: Angiotensin converting enzyme (ACE)-inhibitor overdose may result in severe hypotension. Existing data do not adequately deal with the likely onset of haemodynamic effects, which has implications for the appropriate duration of monitoring in the acute-care setting. Therefore, the relationship between the interval after an ACE-inhibitor overdose and onset of hypotension was examined. METHODS: A retrospective case review of patients who attended our institution after an ACE-inhibitor overdose between 1 January 2000 and 31 December 2005 was carried out. Data collected were heart rate, blood pressure, electrolytes, electrocardiogram variables, and interval between ingestion and lowest recorded blood pressure. RESULTS: 33 patients (24 men) who presented after an ACE-inhibitor overdose were identified. Median (interquartile range (IQR)) age was 49 (42-56) years, and stated quantity ingested was 20 (7-42) times the defined daily dose. The median (IQR) interval between ACE-inhibitor ingestion and lowest recorded systolic blood pressure was 4.5 (3.8-5.5) h, diastolic blood pressure was 3.8 (3.3-6.5) h and mean blood pressure was 4.2 (3.5-5.5) h. Heart rate did not increase substantially in response. CONCLUSION: The lowest blood pressure was recorded within a short interval after an ACE-inhibitor overdose, irrespective of therapeutic intervention. Patients in whom hypotension has not occurred within 6 h of ingestion can be considered for discharge.

Adult↗

Weight loss and fatigue in an elderly patient.

We report a recent clinical case of an elderly patient who presented with weight loss and fatigue and who was diagnosed with hyperthyroidism. Some time later, he was discovered to have underlying oesophageal lymphoma. The latter diagnosis was believed to contribute, at least in part, to his symptoms at the time of initial presentation. The case illustrates the potential difficulties associated with establishing the diagnosis of oesophageal lymphoma. Furthermore, symptoms of weight loss and fatigue are commonly encountered in general medical patients. This case reminded us that even when a diagnosis of hyperthyroidism has been established, these symptoms may be attributable to other pathology.

Aged↗

Hyperuricaemia does not impair cardiovascular function in healthy adults.

OBJECTIVE: To investigate the possibility that uric acid (UA) can impair endothelial function, an important surrogate for atherosclerosis. DESIGN: UA was administered locally or systemically to healthy adult men and women in a series of randomised placebo controlled studies. This temporarily raised serum UA concentrations, so that the potential effects of hyperuricaemia on mechanisms of cardiovascular disease could be studied. MAIN OUTCOME MEASURES: The effects of UA administration on basal blood flow and responses to locally administered acetylcholine, sodium nitroprusside, and L-N(G)-monomethylarginine were studied in the forearm vascular bed with venous occlusion plethysmography. The effects of hyperuricaemia on systemic vascular resistance, large artery compliance, and baroreflex sensitivity were examined by validated non-invasive techniques. RESULTS: UA administration caused a twofold increase in serum concentrations. However, there were no acute effects on haemodynamic variables, basal forearm blood flow, or nitric oxide dependent endothelial function. CONCLUSION: Unlike other risk factors associated with endothelial dysfunction, acute exposure to high concentrations of UA does not impair cardiovascular function in healthy men. These findings do not support a causal link between hyperuricaemia and atherosclerosis.

Acetylcholine↗

Emergency presentation of an elderly female patient with profound hypoglycaemia.

We present the case of an elderly non-diabetic female who was admitted to hospital as an emergency due to loss of consciousness. Her clinical presentation was consistent with hypoglycaemia due to a massive insulin overdose. However, the patient refuted the possibility of insulin administration, and the circumstances were reported to the police for investigation. This case demonstrates the clinical and biochemical characteristics of insulin overdose. Furthermore, it serves to illustrate the sequence of events that may be created when foul play is suspected, and the factors related to patient confidentiality that require consideration by the responsible physician.

Aged↗

Uric acid reduces exercise-induced oxidative stress in healthy adults.

Uric acid (UA) possesses free-radical-scavenging properties, and systemic administration is known to increase serum antioxidant capacity. However, it is not known whether this protects against oxidative stress. The effects of raising UA concentration were studied during acute aerobic physical exercise in healthy subjects, as a model of oxidative stress characterized by increased circulating 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) concentrations. Twenty healthy subjects were recruited to a randomized double-blind placebo-controlled crossover study, and underwent systemic administration of 0.5 g of UA in 250 ml of 0.1% lithium carbonate/4% dextrose vehicle or vehicle alone as control. Subjects performed high-intensity aerobic exercise for 20 min to induce oxidative stress. Plasma 8-iso-PGF2alpha concentrations were determined at baseline, after exercise and after recovery for 20 min. A single bout of high-intensity exercise caused a significant increase in plasma 8-iso-PGF2alpha concentrations from 35.0 +/- 4.7 pg/ml to 45.6 +/- 6.7 pg/ml (P<0.01). UA administration raised serum urate concentration from 293 +/- 16 to 487 +/- 16 micromol/l (P<0.001), accompanied by increased serum antioxidant capacity from 1786+/-39 to 1899 +/- 45 micromol/l (P<0.01). UA administration abolished the exercise-induced elevation of plasma 8-iso-PGF2alpha concentrations. High UA concentrations are associated with increased serum antioxidant capacity and reduced oxidative stress during acute physical exercise in healthy subjects. These findings indicate that the antioxidant properties of UA are of biological importance in vivo.

Adult↗

Systemic uric acid administration increases serum antioxidant capacity in healthy volunteers.

Oxidative stress plays an important role in the development of atherosclerosis and contributes to tissue damage that occurs as a consequence, particularly in myocardial infarction and acute stroke. Antioxidant properties of uric acid have long been recognized and, as a result of its comparatively high serum concentrations, it is the most abundant scavenger of free radicals in humans. Elevation of serum uric acid concentration occurs as a physiologic response to increased oxidative stress-for example, during acute exercise-thus providing a counter-regulatory increase in antioxidant defenses. In view of its antioxidant properties, uric acid may have potentially important and beneficial effects within the cardiovascular system. We wished to investigate whether administration of uric acid was feasible and if it could have an impact on antioxidant function in vivo. We have, therefore, performed a randomized, placebo-controlled double-blind study of the effects of systemic administration of uric acid, 1,000 mg, in healthy volunteers, compared with vitamin C, 1,000 mg. We observed a significant increase in serum free-radical scavenging capacity from baseline during uric acid and vitamin C infusion, using two methodologically distinct antioxidant assays. The effect of uric acid was substantially greater than that of vitamin C.

Adult↗

Angiotropic large B-cell lymphoma with clinical features resembling subacute combined degeneration of the cord.

Angiotropic large cell lymphoma is a rare neoplastic disorder associated with a high mortality. The hallmark of the disease is lymphoid proliferation confined to the intravascular compartment without local tissue or vessel wall infiltration [1]. This feature is so striking that the disease was originally thought to arise from endothelial tissue and early cases were described as malignant angioendotheliomatosis. However, application of immunohistochemical methods for detection of lymphoid markers such as the CD45 and CD20 cell surface markers has confirmed its lymphoid origin, usually of B-cell lineage [2]. Clinical manifestations of the disease are protean and are due to multifocal medium and small vessel occlusion by tumour cells [3]. Characteristic sites of involvement are skin and central nervous system and although an ante-mortem diagnosis can be made from a biopsy specimen, it is often unsuspected [4]. We present a case of angiotropic large B-cell lymphoma in a 74-year-old man who presented with urinary symptoms and had a neurological picture resembling subacute combined degeneration of the cord.

Aged↗