local barrier to the diffusion of the tumour. As we have shown, however, the presence of metastases in regional nodes is not incompatible with a D + or D + + score and long-term survival. Our results confirm those of other series on all histological types of breast cancer, particularly medullary carcinoma (Hamlin, 1968;Bloom et al., 1970;Wernicke, 1972). Other workers have found no correlation between survival and sinus histiocytosis (Berg, 1956;Moore et al., 1960;Kister et al., 1969), follicular hyperplasia (Moore et al., 1960), and lymphocytic infiltration (Morrison et al., 1973) but we believe that the histology of both tumour and lymph nodes must be studied to obtain an accurate picture of host resistance. There is undoubtedly a close relationship between host immunological response and prognosis in the breast cancer. That this response is cell mediated was confirmed by Fisher et al. (1973), who showed that lymphocytes from lymph nodes draining a breast cancer were stimulated in vitro by phytohaemagglutinin. This transformation was associated with follicular hyperplasia and lymphocytic infiltration, whereas no clear-cut correlation could be shown with the presence or absence of sinus histiocytosis.We believe that further studies of the immunological response of lymph nodes draining a tumour removed at operation would provide more information about prognosis (Lancet, 1973). At present we are correlating tumour lymphocytic infiltration and follicular hyperplasia and sinus histiocytosis in regional lymph nodes with preoperative and postoperative lymphocytic responses to phytohaemagglutinin, aspecific and specific delayed cutaneous hypersensitivity reactions, and distribution patterns of T and B cells at tumour and lymph node levels. journal, 1974, 4, 270-271 Though fever has been recognized as a complication of anaesthesia for over 80 years the specific condition of malignant hyperpyrexia has only comparatively recently been described. It is known that susceptible patients, who have been found to have a subclinical myopathy (Harriman et al., 1973), develop a fulminating and often fatal hyperpyrexia when given certain anaesthetic drugs or depolarizing muscle relaxants (Britt and Kalow, 1970). A working definition of malignant hyperpyrexia is an unexplained fever during anaesthesia in which the body temperature rises at a rate of at least 2°C an hour (Keaney and Ellis, 1971). Most patients develop muscle contracture, acidosis, and hyperkalaemia. The condition is inherited as a Mendelian autosomal dominant.

Measurements of complement conversion and white cell variations were made on sequential blood samples obtained from a single volunteer following repeated administration of Althesin. The results suggest a mechanism by which a clinically significant hypersensitivity reaction to the drug might be mediated. Studies of patients receiving routine anaesthesia revealed a very high incidence of subclinical "hypersensitivity" reaction, some of which appear to be immune-mediated. These reactions occurred irrespective of whether the patients were induced with Althesin, methohexitone or propanidid.

SUMMARYIt is not possible to distinguish between direct pharmacological effects and immune-mediated hypersensitivity reactions by clinical observation alone and errors may occur in the absence of laboratory tests. A convenient and simple test is the measurement of plasma complement C3 consumption and conversion in sequential blood samples taken at intervals over the 24 h following an adverse response.Interest in adverse reactions to i.v. anaesthetic agents, particularly those appearing to be related to hypersensitivity, has increased in recent years (Clarke et al., 1975). Reports of reactions to propanidid (Epontol) attributed to hypersensitivity are frequent (Clarke, 1974). Reports of hypersensitivity to thiopentone (Dundee and Wyant, 1974) and methohexitone (Driggs and O'Day, 1972), although fewer than those associated with propanidid, are similar in character. The new steroid anaesthetic, Althesin, has caused a significant number of adverse reactions of the hypersensitivity type (Sutton, Garrett and McArdle, 1974). Unfortunately it is not possible to distinguish readily between direct pharmacological effects and immunemediated hypersensitivity reactions, the latter implying previous sensitization of the patient either to the anaesthetic agent itself or to a cross-reacting antigen. It is important to distinguish the mechanism of the adverse response because (a) the patient may require further anaesthesia at some later date, (b) it affords a critical assessment of the advantages and disadvantages of any new anaesthetic drug and (c) there may be legal implications of death during anaesthesia.Recent investigations have suggested that certain transient changes may occur in the blood of patients who suffer an adverse reaction following the administration of an i.v. anaesthetic agent. Alterations in the concentrations of certain circulating components of the complement system, of immunoglobulin IgE and of white cell numbers have been apparent from serial sampling of blood from such patients (Watkins, Appleyard and Ward, 1975). These changes may be quantitated by simple laboratory techniques. The measurement of consumption and conversion of complement component C3 in sequential blood samples taken over 24 h following an adverse response provides a convenient laboratory assay of the adverse reactions. METHODS Blood samplesVenous blood (5 ml) was collected into a heparinized tube as soon as possible after the onset of the reaction and the time, relative to onset, was noted. Three further heparinized blood samples (5 ml) were collected at convenient times over the next 24 h. A further sample was taken not sooner than 5 days after the event to provide a "base-line" profile of the patient. The plasma was separated from these samples by centrifugation and stored at -20 to -25 °C pending analysis.