Laboratory and clinical features of self-poisoning with salbutamol and terbutaline.

A method has been developed for the simultaneous determination of the sympathomimetic drugs salbutamol and terbutaline in the plasma of poisoned patients, using ion-pair high-performance liquid chromatography with amperometric detection. Plasma concentrations of the drugs, measured in 8 poisoned patients, were well above the therapeutic range. The clinical and metabolic effects of overdose with these drugs were considerably less severe than those seen in patients with plasma theophylline concentrations elevated to the same degree.

Plasma glutathione S-transferase measurements by radioimmunoassay: a sensitive index of hepatocellular damage in man.

Plasma glutathione S-transferase (GST) basic and N/A2b concentrations have been measured by specific radioimmunoassay in serial samples taken from patients admitted following a paracetamol overdose. The activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also measured. The sensitivities of the various measurements for detecting hepatocellular damage were compared. The measurement of either basic or N/A2b GST proved equally sensitive for detecting liver damage and both were superior to aminotransferase measurements. The abnormalities in GST were, on average, approximately 5- to 10-fold greater than the conventional aminotransferase measurements provided that correct timing of sampling was employed. The data presented suggest GST measurement is a sensitive non-invasive method for investigating acute drug-induced hepatotoxicity. The short plasma half-life of GST also allows early recognition of when active cellular damage has ceased.

Comparison of total antibody and interferon-γ T-cell responses in patients following infection with brucellosis in Georgia.

Brucellosis is an ancient disease that still remains a significant threat to humans and is typically linked to exposure to infected animals and/or consumption of unpasteurized animal products. Despite this history, we have a relatively limited understanding of the host characteristics of this disease; consequently, further research is necessary. In this study, we examined the humoral immune response in 43 Georgian individuals that had been diagnosed with brucellosis 3-12 months before enrollment in the study, many of whom still had symptoms after the completion of antibiotic therapy. In total, 35 of 43 (83%) of the patients had antibodies that bound to Brucella lipopolysaccharide (LPS) by COMPELISA, and 34 of 38 (89%) patients had demonstrable specific antibodies to Brucellergene™ antigens; the results from the two ELISAs were highly correlated (p=0.031, r=0.851). We also studied the cellular immune responses in 15 patients. All of the patients generated interferon (IFN)-γ in response to ex vivo stimulation with Brucella protein antigens, and the majority of the patients maintained measurable humoral responses to both LPS and protein antigens. From this initial study, we conclude that measurement of antibody and of cellular (IFN-γ) responses to brucellergene OCB protein epitopes may be worthy of further investigation as an alternative or adjunct to current diagnostics.

Quinine toxicity.

PIP: The currently recognized toxic effects of quinine in humans are identified and the problems of management of overdosage of quinine are discussed. Quinine, available therapeutically as sulphate or hydrochloride salts, also is widely used in tonic water, and there are several case reports of allergic reactions to the drug when a patient has consumed the drug in this way. Another unintentional source of poisoning is its use as an adulterant in heroin for "street" use. This appears to be a problem in the US. Quinine, termed a "general protoplasmic poison" is toxic to many bacteria, yeasts, and trypanosomes, as well as to malarial plasmodia. Quinine has local anesthetic action but also is an irritant. The irritant effects may be responsible in part for the nausea associated with its clinical use. In addition it has a mild antipyretic effect. Several features are common to both an acute single overdose in self-poisoning and accumulation of quinine during therapy for malaria: together they are termed cinchonism. Auditory symptoms, gastrointestinal disturbances, vasodilatation, sweating, and headache occur with moderately elevated plasma quinine concentration. As these rise, increasingly severe visual disturbances and then cardiac and neurologic features occur. Mild nausea may be the only symptom, but with large overdoses profuse vomiting, abdominal pain, and diarrhea may occur. These result from a combination of the local irritant effect of quinine on the gut and the central effects of quinine on the chemoreceptor trigger zone. Vasodilatation and sweating are well recognized, and tinnitus is common. Visual symptoms usually are delayed, and blindness may not be discovered for a day or more. Aspirin-sensitive patients, and others, may develop angioedema by nonimmunological mechanisms in response to drugs, and quinine has been reported to produce pseudo-allergic reactions in aspirin-sensitive patients. Quinine also can cause drug-induced thrombocytopenia and purpura. In patients suffering with malaria due to "Plasmodium falciparum," anemia and acute intravascular hemolysis with renal failure are recognized complications. There appears to be little evidence in the literature in support of the folk tradition of quinine as an inducer of abortion. Quinine is known to cause deterioration in patients with myasthenia gravis and erythema multiforme, to stimulate insulin release in patients receiving treatment for falicparum malaria, and to be responsible at times for ataxia following moderate overdosage. Clinically, quinine poisoning is observed in 3 situations: self-poisoning; accidentally; and following use of quinine in excessive doses in the hope of achieving abortion. Treatment courses are reviewed.^ieng

Management of acute iron poisoning.

Acute iron poisoning is most common in children below the age of 5 years. While there is no doubt that it may be fatal, recent surveys show that death occurs in only a very small percentage of cases and that iron salts are responsible for a small minority of fatalities due to overdosage with drugs. Similarly, the proportion of severe cases seems to have fallen over the last thirty years, possibly due to earlier and more aggressive treatment but more probably due to an increase in the number of minor exposures reported. Iron salts are directly toxic to the gastrointestinal tract causing vomiting, diarrhoea, abdominal pain and occasionally significant blood loss. They also cause metabolic acidosis by interfering with intermediary metabolism and producing shock and reduced tissue perfusion. The clinical course of acute iron poisoning is divided into 4 phases. Features of acute gastrointestinal irritation dominate the period up to 6 hours after ingestion and most patients do not develop other features or progress beyond this stage. Rarely, blood loss may be sufficient to cause hypotension. Severe poisoning is characterised by impairment of consciousness, convulsions and metabolic acidosis. The second phase, 6 to 12 hours after ingestion, is one of remission of features. Phase 3 comprises the period 12 to 48 hours from ingestion and is reached only by a small minority of patients. Recurrence or development of shock, and metabolic acidosis are usual and renal failure and features of extensive hepatocellular necrosis may develop. The last (fourth) phase, 2 to 6 weeks after ingestion, is only likely to develop in young children and is characterised by recurrence of vomiting due to gastric or duodenal stenosis caused by healing of iron-induced mucosal ulcers. Acute iron poisoning in humans has not been adequately studied and is unlikely to be so now because of the infrequent and sporadic occurrence of cases. The evidence for many conventional aspects of management is therefore unsatisfactory. Assessment of severity of poisoning is an essential prerequisite to optimum management but is difficult. The amount of elemental iron ingested is unacceptable since it is seldom known with accuracy and absorption is unpredictable because of vomiting and diarrhoea. The commonly encountered clinical features are also unreliable although it is generally accepted that coma, shock and metabolic acidosis indicate severe poisoning.(ABSTRACT TRUNCATED AT 400 WORDS)

Quinine amblyopia: is current management appropriate?

Thirty-one patients blind from overdoses of quinine are reported. One died from cardiotoxicity. Of the survivors, thirteen received bilateral stellate ganglion block, seven unilateral block, five a variety of other treatments aimed at increasing retinal blood flow, and five no specific treatment. Nine patients recovered vision completely but twenty were left with varying degrees of visual field constriction and one was blind at last follow-up. No treatment for oculotoxicity was of benefit. Since experimental and clinical observations show that the primary toxic effect of quinine is on photoreceptor cells, stellate ganglion block and other vasodilator treatments have no rational basis and should no longer be recommended.

Volumetric control of continuous haemodialysis in multiple organ failure.

A system for precise volumetric control of continuous haemodialysis and its use in providing renal replacement treatment in the intensive care unit to 10 children with multiple organ failure are described. The system, termed slow efficient dialysis, provided effective clearance of urea, creatinine, potassium, and phosphate. It provided precise control of the volume of ultrafiltrate removed in a prospective manner ('dial up' fluid balance) to reduce haemodynamic instability and fluid management problems. The ease of use of this system for intensive care nurses meant that the system ran without the assistance of a second intensive care or renal nurse.

The assessment of cerebral oxygenation during carotid endarterectomy utilising near infrared spectroscopy.

Near infrared spectroscopy is a non-invasive method for continuous monitoring of tissue oxygenation. In 11 patients undergoing unilateral carotid endarterectomy, changes in cerebral oxygenation following carotid cross-clamping and declamping detected by a near infrared spectrometer were compared with corresponding changes in ipsilateral middle cerebral artery flow velocity measured by transcranial Doppler ultrasonography. Spectroscopic traces were obtained in all patients but adequate Doppler signals in only eight. Changes in cerebral haemoglobin oxygenation correlated closely (r = 0.908, p < 0.001) with changes in middle cerebral artery velocity. The near infrared spectrometer was also sensitive to the changes in cerebral haemodynamics due to intraoperative hypo- and hypertensive episodes. No evidence of cerebral intracellular hypoxia was seen and all patients made an uneventful recovery. Near infrared spectroscopy compares well with transcranial Doppler ultrasound as a monitor of cerebral function during carotid endarterectomy and may have a future role in the elucidation of cerebral perfusion and oxygenation changes following surgery.

Severe atenolol poisoning: treatment with prenalterol.

A case of severe self-poisoning with atenolol is described. This did not respond to treatment with atropine and glucagon, but intravenous prenalterol resulted in rapid improvement.

Self-poisoning and therapeutic intoxication with lithium.

Of 68 admissions for lithium overdose over 16 years, 25 were due to therapeutic intoxication and 43 to deliberate self-poisoning. Three patients with therapeutic intoxication had acute diabetes insipidus with hypernatraemia. One of them had acute renal failure requiring dialysis, prolonged Parkinsonism and generalised myopathy. Twenty-two patients with therapeutic intoxication had peak serum lithium concentrations above the therapeutic range. In contrast, of 22 self-poisoned patients with peak serum lithium concentrations above the therapeutic range only 3 developed toxicity. The mean admission plasma urea concentration in patients with therapeutic intoxication was higher than in self-poisoned patients and the mean admission plasma bicarbonate concentration was lower. The mean serum lithium half-life in 8 patients with therapeutic intoxication was considerably longer than in 5 self-poisoned patients. Renal lithium clearance is enhanced by increased sodium excretion and we recommend that lithium toxicity be treated with saline diuresis and frusemide if fluid retention occurs. Haemodialysis is mandatory when renal failure is present, and may be indicated when serum lithium concentrations are very high or rising rapidly.

Plasma glutathione S-transferase measurements after paracetamol overdose: evidence for early hepatocellular damage.

Plasma glutathione S-transferase (GST) measurements have been used to study early changes in hepatocellular integrity after paracetamol overdose and treatment with N-acetylcysteine (NAC). Patients admitted within seven hours and successfully treated had raised or equivocal GST on admission and each showed a transient peak in GST approximately 12 hours after the overdose. Similar, though smaller changes in GST, were seen in untreated patients whose paracetamol level fell below the treatment line. The plasma GST concentrations in successfully treated patients were small compared with values found in patients who subsequently developed severe liver damage. The changes in GST concentration observed in patients who developed severe liver damage indicated that distinct early and late phases of paracetamol-induced hepatotoxicity occurred. Although the mechanism by which paracetamol exerts its early toxic effect is unclear, our data suggest that prompt treatment with NAC can successfully prevent both clinical and subclinical hepatotoxicity in this early period.

Death and blindness due to overdose of quinine.

During 1953-83 there were 48 admissions to the regional poisoning treatment centre, Edinburgh, for overdose of quinine including 19 since 1978. Six patients were blind and one had ventricular tachycardia. Stellate ganglion block was performed without benefit in seven patients. No patient died, but three deaths from cardiotoxicity occurred in a further 71 patients reported to the Scottish Poisons Information Bureau. Plasma quinine concentration related to time from ingestion was found to be a useful predictor of visual toxicity.

Volumetric control of continuous haemodialysis in multiorgan failure.

The authors have developed a system for volumetric control of continuous haemodialysis. The article describes this system and reports its successful use in providing renal support in the intensive care unit to 10 patients with multiorgan failure. In addition to providing effective treatment of uraemia, it permits the precise control of fluid balance in a prospective manner ("dial-up" fluid balance) while reducing nursing workload.

Use of the urinary protein creatinine index to assess proteinuria in renal transplant patients.

The use of 24-h urine protein collections for the assessment of proteinuria in renal transplant patients has been compared with the protein creatinine index (PCI) obtained from spot urine samples. Paired data from 148 patients showed a correlation of 0.77 (P less than 0.001) between 24-h protein excretion and the PCI. A PCI of 750 identified proteinuria of greater than 1.0 g/24 h with a sensitivity of 89% and a specificity of 93%. The predictive value of a positive test was 81% and that of a negative test 96%. Similar performance was observed for the detection of proteinuria of differing severities ranging from 0.5 g/24 h to 2.0 g/24 h. The use of spot testing was popular with both patients and staff, and reduced the sample handling cost to 15% of that of 24-h urine collection. We recommend that PCI be adopted as the standard outpatient test for the assessment of proteinuria following renal transplantation.