Cytokines in anaesthesia

The scope of cytokine biology is fascinating with widespread applications anticipated in many areas of medical science. We have emphasized the fundamental roles that cytokines play in the control of normal immunological functions, defence mechanisms and normal cell growth, and how major surgery and trauma can affect these processes. It remains to be determined if morbidity and mortality may be improved after major illness and surgery by altering cytokine production and function.      

Fentanyl and the interleukin-6 response to surgery

It has been suggested that large doses of opioids may suppress the interleukin-6 response to surgery. We examined the effects of the supplementation of inhalational anaesthesia with either 3 or 15 μg.kg⁻¹ fentanyl on the circulating interleukin-6, interleukin-8, C-reactive protein, cortisol and glucose concentrations in 16 patients undergoing pelvic surgery. In both groups, surgery evoked the expected glucose, cortisol and interleukin-6 response but no increase in interleukin-8 was detected. There were no significant differences between the two groups. We conclude that the supplementation of inhalational anaesthesia with conventional doses of opioids does not modify the cytokine response to surgery.     

Modulation of human T cell functions by surface sulphydryl groups: differential effects on IL-2 production and responsiveness.

An impermeable thiol blocker has been used to investigate the role of sulphydryl (SH) groups in the production of and responsiveness to IL-2 by normal human T lymphocytes. Surface SH blockade of mononuclear cells prior to incubation with mitogen (phytohaemagglutinin, concanavalin A, CD3 MoAb) had no effect on production of IL-2 but markedly impaired cellular responsiveness to exogenous IL-2. Studies using MoAbs indicated that this effect was accompanied by decreased expression of both the CD25 and p75 subunits of the IL-2 receptor. Blocking surface SH groups did not affect binding of IL-2 to p75 on unstimulated mononuclear cells, but inhibited binding to high-affinity receptors on a T lymphoma cell line. The data are consistent with the hypothesis that sulphydryl groups on the IL-2 receptor are required for its function and may be involved in the interaction of the CD25 and p75 subunits leading to generation of the high-affinity binding site. The surface thiol identified on the IL-2 receptor may be a candidate for oxidation on cells from patients with chronic inflammatory diseases such as rheumatoid arthritis and thus contribute to the aberrant function of T cells in these patients.     

Keratan sulphate in rheumatoid arthritis, osteoarthritis, and inflammatory diseases.

Serum concentrations of antigenic keratan sulphate determined by an enzyme linked immunosorbent assay (ELISA) with a monoclonal antibody were studied in patients with rheumatoid arthritis (RA), osteoarthritis, ankylosing spondylitis, other inflammatory diseases, and a large control group of women without arthritis. Mean keratan sulphate concentrations were low in 117 women with RA compared with 227 female control subjects matched for age drawn from a community survey. There were significant correlations between serum keratan sulphate concentrations in patients with RA and serum C reactive protein and the erythrocyte sedimentation rate. Serum keratan sulphate concentrations were also low in 29 men and women with ankylosing spondylitis and 29 patients with arthritis and high concentrations of C reactive protein. In 98 women undergoing an operation for benign breast disease there were decreases in serum keratan sulphate concentrations after the operation which correlated with doses in serum C reactive protein. No differences were found in keratan sulphate concentrations in 137 women with osteoarthritis compared with controls. Within the group with osteoarthritis there were no differences for the various joint groups and there was no obvious correlation with radiographic severity or progression. These findings suggest serum keratan sulphate is unlikely to be useful as a diagnostic marker in osteoarthritis or RA but indicate a role for inflammation in the regulation of cartilage loss.     

Epidemiology and laboratory diagnosis of infection with viral and bacterial pathogens in infants hospitalized for suspected sepsis

A prospective study was conducted to determine the frequency and distribution of bacterial and viral pathogens in infants hospitalized with suspected sepsis and to evaluate the potential of virus detection for improving patient management. A causative organism was detected in 157 (67%) of 233 previously healthy infants less than 3 months of age, who had been hospitalized for suspected sepsis: 19 (8%) had bacterial infections, 135 (58%) had viral infections, and 3 (1%) had mixed viral-bacterial infections. Viral infections occurred in a seasonal pattern: enteroviruses were responsible for most of the hospitalizations during summer and fall (65/110; 63%) and respiratory syncytial and influenza A viruses were responsible for most of the infections during winter (44/81; 55%). In contrast, bacterial infections were not seasonally distributed. Virus was detected in 33% of the 138 infected infants within 24 hours, and in 64% within 3 days. We conclude that viral infections are prevalent among infants hospitalized for suspected sepsis, and most can be detected early enough to influence patient management.     

Neuro-otologic evaluation of the patient with acute, severe head injuries: correlations among physical findings, auditory evoked responses, and computerized tomography

Long-term clinical neurologic and otologic sequelae of traumatic head injury are well recognized. In this article, we describe the relationship among neurophysiologic, neuro-otologic, and neuroradiologic findings in a series of fifty patients with acute, severe head injury. Seventy percent of the patients had one or more otologic abnormalities, of which hemotympanum was most common. Outcome of computerized tomography (CT), auditory brainstem response (ABR), and otologic examination findings were not mutually dependent. For example, otologic disease was found in 50% of the patients with normal ABR. All but one patient in the series showed brain damage by CT; yet only 14% of the series had evidence of temporal bone fracture and, unexpectedly, one third of this group yielded normal otologic findings and a normal ABR. We conclude that combined application of otologic examination, CT scanning, and auditory evoked response assessment provides complementary information on structural and functional neuro-otologic status in persons with acute, severe head injury.     

Gastro-oesophageal reflux and intestinal malrotation in children

In a series of 74 children undergoing Nissen fundoplication for persistent gastro-oesophageal reflux unresponsive to intensive medical treatment, there was an unexpectedly high incidence (54 per cent, n = 40) of intestinal malrotation. The series was not homogeneous, 25 of the children having reflux as a complication of a serious congenital abnormality (48 per cent incidence of intestinal malrotation), and 49 presenting with 'idiopathic' reflux (57 per cent incidence of intestinal malrotation). Intestinal malrotation is best detected pre-operatively by careful barium radiology, requiring clinicians to be aware of the association. In our experience, in children over the age of 3 months, both an antireflux operation and Ladd's procedure are often necessary to stop gastro-oesophageal reflux when an intestinal malrotation is present.