Pituitary-adrenocortical function in treated Hodkgin disease

1407

research institute such as those of the UK, USA, and Australia. Most of the equivalent medical science is to be found in medical school departments and is funded from programme and project grants of the MRC, for which total annual expenditure is $NZ 8690 000). The department of community health in the Auckland School of Medicine, which has six university-funded staff led by Prof Robert Beaglehole, has in the past three years reported a total of forty-six new research grants, the value totalling $NZ 2765 407. If this is neglect, give me excess of it.

J.

Department of Physiology, University of Auckland, Auckland, New Zealand

D. SINCLAIR,

Former scientific secretary, Medical Research Council of New Zealand

Music in the

operating-room

SIR,--Operating-room noise levels are often high enough to interfere with communication among the theatre team, to increase patient apprehension and stress, and to divert attention or to cause irritability, resulting in compromised patient safety. In the United States background music is often chosen and provided by the principal surgeon who may arrive in the operating room with his own radio or tape, or compact disk player. Strict operating room electrical codes do not seem to apply, and these machines are rarely inspected for ground leakage and electrical faults and are usually powered by improvised electrical cords. Record players are sometimes purchased for a favoured operatingroom staff by a frequently visiting surgeon. While low-volume background music is probably helpful in relieving stress, noisy music is not. Some kinds of music are soothing, some are not. Music played loud enough to be perceptible may induce tranquillity in some and be annoying to others. We have yet to discover one of these record machines that was provided by an anaesthetist. Mr Hodge and Mr Thompson (April 14, p 891) are surgeons. While there is no doubt that a startling noise can result in a slip of the knife, we suggest that the anaesthetist attempting to listen to cardiac and respiratory sounds through a stethoscope and pay attention to a myriad of audiovisual alarms is impeded by continuous noise and by startling sounds. Monitor alarms are intended to be intrusive and annoying, although more easily recognised and specific alarms are being developed. Operating rooms are too noisy; radios and record players are not necessary to the surgical procedure and can easily be eliminated. Department of Anesthesia, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA

ARTHUR J. L. SCHNEIDER JULIEN F. BIEBUYCK

Cardiac arrest telephone numbers SIR,-Delay in the arrival of the resuscitation team to a patient with cardiopulmonary arrest will affect outcome, and this has clearly been shown for out-of-hospital cardiac arrest.1 The telephone code which hospital staff dial to summon the resuscitation team is not standardised in the UK even though doctors and nurses change jobs. When we asked 100 UK hospitals (20 selected at random from

Pituitary-adrenocortical function in treated Hodkgin disease SIR,-Dr Razavi and colleagues (April 21, p 931) report a significant impact of psychosocial factors, especially distress, on outcome of patients with breast cancer. They conclude that changes in the neuroendocrine system may be the major link between emotional processes and the course of cancer. We decided to investigate hormonal indices known to be influenced by psychosocial factors in the context of other malignant diseases. Within a trial comparing two chemotherapy regimens (plus radiotherapy) in patients with Hodgkin disease1 we did a pilot study on 21 men aged 18-48 years at between 4 months and 13 years after the end of treatment. Matched healthy individuals served as controls. Corticotropin (ACTH) and cortisol levels were measured before and after stimulation with 100 I-lg corticotropin-releasing hormone (CRH; Bissendorf Peptide, Wedemark) given intravenously. We also measured baseline levels of luteinising hormone (LH), follicle-stimulating hormone (FSH), prolactin, testosterone, and 17 a-hydroxyprogesterone (17-OHP). All tests were done between 0800 and 1100 hours. Statistical evaluation was done by Wilcoxon (within group) and Dunn (between group) tests. After both treatment regimens, patients differed from controls in having increased baseline levels of LH, FSH, and prolactin. However, FSH increased by less in patients on ABOEP (see table) than in those on COPP regimen, which confirms the reduced long-term toxicity of ABOEP.* For both groups together ACTH levels 60 min before stimulation were above normal (p < 005) but fell to normal by time zero. Patients had increased cortisol levels 60 min before CRH (p < 0 005); cortisol levels fell during the run-in but and in controls (p<0001), period in patients (p < 001) remained higher in the patients. Baseline 17-OHP was also increased in the patients. In controls, CRH stimulation resulted in gross increases in ACTH and cortisol while in patients the ACTH response was blunted; the change in cortisol was less than that in the controls (p < 001) but a response was still present (p < 005). Thus, independently of the chronic toxicity of the cytotoxic regimen, these patients with Hodgkin disease had a response to CRH stimulation resembling that found in patients with depression.2,3 This response pattern may indicate chronic cortisol excess brought about by persistent overstimulation of the pituitaryadrenocortical axis by an abormality at the hypothalamic or suprahypothalamic level.4 An increase in 17-OHP, a steroid precursor, indicates increased ACTH activity and rules out the possibility that the hypercortisolaemia in our patients was caused by decreased cortisol turnover. As in patients with other malignant diseases,’ prolactin levels were high. We do not know whether these hormonal alterations arise from the Hodgkin disease (or other malignancy), from the fact of chronic severe illness, from the BASELINE HORMONE LEVELS AND ACTH AND CORTISOL BEFORE AND AFTER STIMULATION

Scotland, Wales, and Northern, West Midland, and Metropolitan regions of England) we found that thirty codes were in use. Up to twelve codes were in use in a single area. The most common were 222 (33%) and 333 (19%); the others were 2222 (10%), 666 (5%), other repeated digit (15%), and multiple differing digits (18%). There is

a

strong

case

for

a

standardised national cardiac

arrest

telephone code, preferably a single repetitive digit, as for the public emergency services number (999). Our own modem switchboard tells us that changing our code (333) to another is simple. The major problem would be publicity. We recommend the adoption of 222 for the cardiac arrest code in UK hospitals.

South Cleveland Hospital, Middlesbrough TS4 3BW, UK

P. Z. E. P.

M. ROTHWELL F. UDWADIA

A. JACKSON G. LAWLER

1 Eisenberg M, Hallstrom A, Bergner L. The ACLS score. Predicting out-of-hospital cardiac arrest. JAMA 1981; 246: 50-52

outcome

from

*p < 05, tp < 0 01, †p < 005. p< 0-001 vs controls, . p<0 0 05 vs COPP ABOEP =’Adriamycin’, vincristine, prednisone ; bleomycin, etoposide, COPP = Cyclophosphamide. vincristine, procarbazine, prednisone

1408

patient’s knowledge of the diagnosis and its implications, or from cytotoxic (or other unpleasant) treatment, or from the patient being under continuous medical care. The essential questions-how do emotional damage and psychosocial distress induce such striking changes in endocrine function and how might these changes affect outcome-are beyond the scope of our pilot study. E.

Departments of Endocrinology and Haematology, Centre of Internal Medicine, Johann Wolfgang Goethe University, D-6000 Frankfurt am Main, West Germany

JUNGMANN

J. BINDER U. JESTÄDT P. S. MITROU P.-H. ALTHOFF K. SCHÖFFLING

1. Mitrou PS, Hechler P, Kippstein T, Lautenschlager G, Burkhardt KL, Jungmann E. Chemotherapy with adriamycin, bleomycm, vincristine, etoposide and prednisone + radiotherapy in Hodgkin’s disease. 5th European Congress of Clinical Oncology (London, Sept 2-7, 1989). 2. Gold PW, Loriaux DL, Roy A, et al. Responses to corricotropin-releasing hormone in the hypercortisolism of depression and Cushing’s disease. N Engl J Med 1986; 314: 1329-35. 3. von Bardeleben U, Wiedemann K, Holsboer F. Altered brain-pituitary-adrenocortical activity in major depression. In: Casanueva FF, Dieguez C, eds. Recent advances in basic and clinical neuroendocrinology. Excerpta Med Int Congr Ser 1989; no 864: 357-67. 4. Jungmann E, Remer P, Luderer E, et al. Postoperative evaluation of adrenocortical function by a corticotropin-releasing factor test in patients with large pituitary adenomas. In: Landolt AM, Heitz PU, Zapf J, et al, eds. Advances in pituitary adenoma research. Oxford: Pergamon, 1988: 431-32. 5. Kleinberg DL. Prolactin and breast cancer. N Engl J Med 1987; 316: 269-71.

Psychological correlates of hormone receptor status in breast cancer SIR,-Dr Razavi and his colleagues (April 21, p 931) report greater psychological distress in patients with receptor-negative breast cancers than in those with receptor-positive tumours, and suggest that these findings may account for the association between psychosocial variables and survival in this disease. Unfortunately there is a potential source of bias in Razavi and colleagues’ data which may affect the validity of their conclusions. The initial psychological evaluation was undertaken during "the first days of radiation therapy" and at a mean of more than 3 months after diagnosis. Razavi et al report that 10 (56%) of 18 patients with receptor-negative tumours received chemotherapy whereas 30 (40%) of 75 with receptor-positive tumours did so. Even though this difference was not significant such imbalances could have sufficient influence on psychological distress, as measured by a self-report scale (SCL90-R), to invalidate the reported fmdings.At least 20% of the 90 items in this scale are directly concerned with somatic symptoms such as nausea and upset stomach, feeling weak, low energy, and poor appetite. Higher scores recorded for such items in the receptor-negative group may simply reflect the toxicity due to chemotherapy, Patients undergoing adjuvant chemotherapy emotional symptoms such as tearfulness and hopelessness than those who do not.2 The possibility that receptor status may determine the putative relation between psychosocial variables and disease outcome in breast cancer is, however, of interest. We have reportedthe findings of a case-control study of the frequency of stressful life experiences in 50 patients with a first recurrence of breast cancer and in 50 controls who remained in remission. The patients and controls were matched on a pair-wise basis for the main physical and pathological factors known to be of prognostic importance in breast cancer, including axillary lymph-node status and histological grade of tumour. Oestrogen receptor (ER) status was not used for matching since some pairs had first presented before such measurement was routinely,available. The main findings were that women whose breast cancer had relapsed were significantly more likely to have had severe adverse life events or continuing difficulties than were their matched controls. Further group-wise analysis of the data from this study has now been undertaken to assess the possible influence of ER status on the relation between severe life events and relapse. When all patients were considered, 26 women who relapsed had a severe life event also have

more

whereas 12 of those in remission did so (p = 0-007). Among the 57 patients with ER-positive tumours, 14 of the 26 who relapsed and 3 of the 31 who remained in remission had had a severe life event (p = 0-0004). Among the 15 patients with ER-negative tumours, 2 of the 8 who relapsed and 3 of the 7 who remained in remission had had a severe life event (p=0-6). These findings are clearly preliminary but support the hypothesis that the effect of psychosocial variables on outcome is mediated via a hormonal mechanism. AMANDA J. RAMIREZ MICHAEL A. RICHARDS WALTER GREGORY THOMAS K. J. CRAIG

ICRF Clinical Oncology Unit and Division of Psychiatry, United Medical and Dental Schools, Guy’s Hospital, London SE1 9RT, UK

1. Altman DG. Comparability of randomised groups. Statistician 1985; 34: 125-36. 2. Ramirez AJ. Psychological strategies in patient care. In: Fentiman IS, ed. Detection and treatment of early breast cancer. London: Martin Dunitz, 1990: 140-53. 3. Ramirez AJ, Craig TKJ, Watson JP, Fentiman IS, North WRS, Rubens RD. Stress and relapse of breast cancer. Br Med J 1989; 298: 291-93.

Phosphate and rickets SIR,-Dr Holland and his colleagues (March 24,

p 697) relate babies to prenatal phosphate deficiency. Their demonstration that hypercalciuria is associated with phosphate deficiency fits in with data in older children and adults with hypercalciuria.’ However, I have reservations about their method of assessing renal tubular phosphate handling. They calculated the percentage tubular reabsorption of phosphate (% TRP) and found a difference between those babies with radiological rickets subsequently and those without. Unfortunately this index is influenced by the filtered load of phosphate (and thus plasma phosphate), which may vary in immature babies. The % TRP cannot therefore be regarded as the most sensitive index of renal tubular phosphate handling. Similarly the TmP/GFR formula of Brodehl,2referred to by Holland et al in the discussion, can vary directly with plasma phosphate, so it is not surprising that they found a high correlation betwen TmP/GFR and plasma phosphate. The theoretical phosphate threshold TmP04/GFR proposed by Bijvoet3 remains the most sensitive index since it is independent of plasma phosphate and glomerular filtration. Recalculation of the TmP04/GFR from Holland et al’s data could be easily done and might influence the interpretation of the results, though the same differences could still be seen. In their final paragraph Holland et al state that "low plasma phosphate concentration and reduced tubular reabsorption of phosphate identified babies with impaired bone mineralisation". Surely they mean increased tubular reabsorption of phosphate?

rickets in

very-low-birthweight

Institute of Child Health, Royal Liverpool Children’s Liverpool L12 2AP, UK

Hospital,

N.J. SHAW

1. Editorial. Idiopathic hypercalciuria: new thoughts on the phosphate connection. Lancet 1987; i: 1412-13. 2. Brodehl J, Krause A, Hoyer P. Assessment of maximal tubular phosphate reabsorption: comparison of direct measurement with the nomogram of Bijvoet. Paediatr Nephrol 1988; 2: 183-89. 3. Bijvoet OLM. Indices for the measurement of the renal handling of phosphate. In: Massry SG, Fleisch H, eds. Renal handling of phosphate. New York: Plenum, 1980: 1-37.

*** This letter has been shown whose reply follows.-ED. L.

to

Dr Holland and his

colleagues,

SIR,-Dr Shaw is right to point out that the last paragraph of our paper should have referred to reduced renal tubular reabsorption of calcium (not phosphate) which identified babies with impaired bone mineralisation. The renal tubular phosphate handling was similar in the babies in whom rickets later developed and those in whom it did not, in that all (except one baby who had severe asphyxia) conserved phosphate with a tubular reabsorption of over 95% when plasma phosphate fell