Therapeutic glucocorticoids prevent bone loss but drive muscle wasting when administered in chronic polyarthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) experience extra-articular manifestations including osteoporosis and muscle wasting, which closely associate with severity of disease. Whilst therapeutic glucocorticoids (GCs) reduce inflammation in RA, their actions on muscle and bone metabolism in the context of chronic inflammation remain unclear. We utilised the TNF-tg model of chronic polyarthritis to ascertain the impact of therapeutic GCs on bone and muscle homeostasis in the context of systemic inflammation. METHODS: TNF-tg and wild-type (WT) animals received either vehicle or the GC corticosterone (100 µg/ml) in drinking water at onset of arthritis. Arthritis severity and clinical parameters were measured, serum collected for ELISA and muscle and bone biopsies collected for µCT, histology and mRNA analysis. In vivo findings were examined in primary cultures of osteoblasts, osteoclasts and myotubes. RESULTS: TNF-tg mice receiving GCs showed protection from inflammatory bone loss, characterised by a reduction in serum markers of bone resorption, osteoclast numbers and osteoclast activity. In contrast, muscle wasting was markedly increased in WT and TNF-tg animals receiving GCs, independently of inflammation. This was characterised by a reduction in muscle weight and fibre size, and an induction in anti-anabolic and catabolic signalling. CONCLUSIONS: This study demonstrates that when given in early onset chronic polyarthritis, oral GCs partially protect against inflammatory bone loss, but induce marked muscle wasting. These results suggest that in patients with inflammatory arthritis receiving GCs, the development of interventions to manage deleterious side effects in muscle should be prioritised.

The gastric tonometer. A valuable monitor of splanchnic perfusion?

Minimally invasive assessment of the adequacy of perfusion of the gastrointestinal tract has become clinically feasible with the availability of the gastric tonometer. This modified nasogastric tube permits calculation of the pH of the gut mucosal cells; a low tissue pH may indicate tissue hypoxia due to regional hypoperfusion. Such regional hypoperfusion is often undetected by other monitors and, if it occurs intra-operatively, may result in a poor outcome following major surgery. In critical illness, the splanchnic area seems to be particularly vulnerable to hypoperfusion and such a regional oxygen deficit is implicated in the causation of organ dysfunction/failure. Recent studies have begun to define the circumstances in which splanchnic tissue acidosis develops and several therapies have been proposed to reverse the regional oxygen deficit. This review seeks to clarify whether or not the tonometer is a valuable addition to our current monitoring aids.

Intensive care management of multiple-organ dysfunction due to falciparum malaria in a married couple.

A married couple presented simultaneously with malignant tertian malaria and rapidly developed septicaemia and severe multiple-system organ failure. Despite schizonticidal treatment and multisystem support in intensive care the husband died. The selection of chemoprophylactic agents for this couple was not ideal and the duration of therapy before exposure to risk was inadequate. Severe infection with plasmodium falciparum is life-threatening and requires early diagnosis. It is best managed in an intensive care unit where continuous assessment may enable rapid detection of clinical deterioration and allow appropriate treatment to be instituted. The diagnosis should be considered in symptomatic patients who have travelled through areas where malaria is endemic. Recognised guidelines for the prescription of malarial chemoprophylaxis should be followed to ensure adequate protection.

Vecuronium and atracurium in the elderly: a clinical comparison with pancuronium.

The intubating conditions, time to complete block and duration of clinical relaxation were observed in a group of 101 elderly patients (aged over 65 years) following pancuronium 0.1 mg kg-1, vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1. The intubating conditions in the three groups were similar when assessed at 2 min following relaxant administration. The time to complete block was shortest with vecuronium (4.3 min) in comparison to atracurium (5.0 min) and pancuronium (6.0 min), but the differences were not statistically significant. The duration of clinical relaxation, however, was significantly shorter with vecuronium (37 min) and atracurium (35 min) in comparison to pancuronium (99 min).

Histaminoid responses to atracurium, vecuronium and tubocurarine.

Sixty patients scheduled for elective surgery underwent intradermal testing with 0.1 ml of the following solutions diluted in 0.9% saline: vecuronium and tubocurarine (1 in 1,000), atracurium (1 in 1,000 and 1 in 10,000), thiopentone (1 in 100) and also a 0.9% saline control. Thirty minutes later, an area of erythema of greater than 1.5 cm, or a wheal exceeding 1.0 cm in diameter, was recorded as a positive reaction. The patients then randomly received equipotent doses of atracurium, vecuronium or tubocurarine during a standardized anaesthetic induction. Any cutaneous reaction and the percentage fall in systolic pressure three minutes after administration of the relaxant were recorded. In 51 patients plasma IgE levels were measured. The incidence of positive cutaneous reactions to intradermal and intravenous relaxants was significantly different with each agent (p less than 0.01). The percentage fall in systolic pressure after tubocurarine was significantly different relative to the other two agents (p less than 0.01). This was regarded as reflecting potency in releasing histamine and placed the relaxants in the same order: tubocurarine, atracurium and vecuronium. The response to intradermal administration was no guide to the subsequent response after intravenous administration of the three relaxants. IgE levels below 15 IU X ml-1 occurred significantly more often in females and were associated with a significantly higher incidence of cutaneous reactions after intradermal atracurium (1 in 1,000 and 1 in 10,000) (p less than 0.05 and 0.001 respectively) and tubocurarine (1 in 1,000). With these two agents, generalized flushing after intravenous administration was also more common in this group, relative to the normal/high IgE group.

Atracurium besylate in paediatric anaesthesia.

Atracurium was evaluated in clinical anaesthesia in 50 children undergoing elective surgery. The time to onset of maximum block (182 seconds) was similar to that of vecuronium but shorter than that of pancuronium as previously reported. The duration of clinical relaxation (33 minutes) is between those of vecuronium and pancuronium. The antagonism of block at 25% recovery was easy. There was no untoward cardiovascular effects but skin reactions were observed in over 30% of patients.