47

however, that one of these alternative explanations should beconsidered in more detail-namely, that class-related psychosocialstresses in early life (including labour-market stress in youngadulthood) may increase the risk of IHD later on.

Several studies indicate that both stressful life events andstress-related symptoms are substantially more common in thelower social classes,l-4 and job-related stresses are associated withchanges in serum cholesterol, cardiac arrhythmias, and increasedrisk of myocardial infarction.5-9Some workers have argued that early economic stress and labour

market experience may affect the lifelong risk of IHD. Bunn10traced the epidemic increase in Australian IHD mortality, peakingin 1968, back to the economic stresses of the 1930s.1O Eyer andSterling" argue, conversely, that the labour market experience ofmembers of the post-war US baby-boom cohort predisposed themto an increased risk of death from a variety of stress-related illnesses.

Class-related psychosocial stress in early life, amplified by thepoverty of unemployment in the 1930s may account for thegeographical association of infant mortality rates in 1921-25 andIHD mortality some 50 years later.

Mental Health Centerof Boulder County, Inc,

Boulder, Colorado 80302, USA;and Institute of Behavioral Science,

University of Colorado RICHARD WARNER

1. Coates D, Moyer S, Wellman B. The Yorklea study of urban mental health:Symptoms, problems and life events. Can J Publ Health 1969; 60: 471-81.

2. Myers JK, Lindenthal JJ, Pepper MP. Social class, life events and psychiatricsymptoms: a longitudinal study. In: Dohrenwend BS, Dohrenwend BP, eds.Stressful life events: their nature and effects. New York: Wiley, 1974.

3. Dohrenwend BS. Social status and stressful life events. J Pers Soc Psychol 1973; 28:225-35.

4. Pearlin LI, Radabaugh CW. Economic strains and coping functions of alcohol. Am JSocial 1976; 82: 652-63.

5. Rabkin SW, Mathewson FAL, Tate RB. Chronobiology of cardiac sudden death inmen. JAMA 1980; 244: 1357-58.

6. Russek HI, Zohman BL. Relative significance of heredity, diet and occupational stressin coronary heart disease of young adults. Am J Med Sci 1958; 235: 266-77.

7. Floderus B. Psychosocial factors in relation to coronary heart disease and associatedrisk factors. Nord Hyg Tidskr 1974; suppl 6.

8. Friedman M, Rosenman RH, Carroll V. Changes in the serum cholesterol and bloodclotting time in men subjected to cyclic variation of occupational stress. Circulation1958; 17: 852-61.

9. Theorell T. Life events before and after the onset of a premature myocardial infarction.In: Dohrenwend BS, Dohrenwend BP, eds. Stressful life events: their nature andeffects. New York: Wiley, 1974.

10. Bunn AR. Ischemic heart disease mortality and the business cycle in Australia. Am JPubl Health 1979; 69: 772-81.

11. Eyer J, Sterling P. Stress-related mortality and social organization. Rev Radical PolitEcon 1977; 9: 1-44.

DEPRESSION IN MEDICAL PATIENTS

SiR,—Your April 26 editorial on the neglected problem ofdepression in the medically ill failed, in its enthusiasm for "a moreactive approach", to acknowledge the complexity of diagnosingdepression in the medically ill and it misrepresented our studyl as astatement of therapeutic nihilism.

It is difficult to diagnose depression in the face of majormedical-surgical illness; many of the usual signposts, particularlyvegetative functions, are confounded by the physical illness. Onecannot rely on impaired sleep and appetite, weight loss, reducedenergy, and the like to diagnose mood disorder in the medically ill.Your editorial gives no hint of this. On the contrary, it uncriticallyendorses screening questionnaires which emphasise vegetativecriteria to diagnose depressive constellations. Our study wasrestricted to medical-surgical inpatients with identified majormedical illness and severe depressive features. We did not includepatients with marginal symptoms. The extent of our patients’ mooddisturbances left little doubt that intervention was advisable, despiteinherent diagnostic dilemmas.Only 40% of patients in our study responded favourably to

antidepressants; 32% of trials had to be discontinued because ofside-effects. We suggested that "clinicians confronted with depress-ive syndromes in the medically ill should fully consider forms ofintervention other than tricyclic antidepressants". This is not

equivalent to your editorial’s contention that we questionedwhether a diagnosis of affective illness in medical patients "reallymatters". We closed our paper by noting "the compelling need forsystematic, controlled studies of the treatment of depressivedisorders in the medically ill". Costa and colleagues’ trial,2 cited inthe editorial, was ofmianserin, a drug not yet available in the UnitedStates, and appears to be such a study. We see nothing in it thatconflicts with our findings.The case for a more active approach to the treatment of

depression in medical inpatients is not open and shut as youreditorial implies. It requires careful, reasoned investigations, notmerely good intentions. As yet, we know little of the risk factors,natural course, and treatment response of these depressive disturb-ances or whether they constitute a discrete clinical entity. Equallyproblematic are the disinterest and lack of rigour shown bynon-psychiatric physicians in their use of antidepressants 3,4 Urgingprimary-care physicians to charge ahead without a clear data baseand an appreciation of the diagnostic and clinical points at issue is adisservice to both practitioners and their patients.

Department of Psychiatry,University of Minnesota Hospitals,Minneapolis, Minnesota 55424, USA

M. K. POPKINA. L. CALLIEST. B. MACKENZIE

1. Popkin MK, Callies AL, Mackenzie TB. The outcome of antidepressant use in themedically ill. Arch Gen Psych 1985; 42: 1160-63.

2. Costa D, Mogos J, Toma T. Efficacy and safety of mianserin in the treatment ofdepression of women with cancer. Acta Psychiatr Scand 1985; 72 (suppl 320):85-92.

3. Davidson RJ, Raft D, Lewis BF, Gebhardt M. Psychotropic drugs on general medicaland surgical wards of a teaching hospital. Arch Gen Psych 1975; 32: 507-11.

4. Mayou R, Smith EBO. Hospital doctors management of psychological problems. Br JPsychiatry 1986; 148: 194-97.

VISUAL FUNCTION IN THE NEWBORN

SIR,-Dr Dubowitz and her colleagues’ view (May 17, p 1139)that visual tracking responses in newborn babies are not corticallymediated is consistent with the proposal that the control of suchfunctions in the newborn is vested in the superior colliculus,lalthough the ability to switch attention between targets may involvethe cortex.2 Contrary to that contention, we consider that neonatalelectrophysiological visual responses are cortically based.The similar sequences of development of the flash visual evoked

potential (VEP) in the kitten3 and in newborn babies suggest thatthe early development of the primary visual system may be similarin both, although the organisation of the mature system differsbetween cats and primates. In the developing VEP a broad negativewave of long latency predominates at an early stage, later

diminishing,4 while a positive wave of shorter latency appears ataround 33 weeks’ gestation in man and 10 days in the cat .3 Inkittens the negative wave may be recorded over the occipital cortex(OC) following stimulation of the superior colliculus (SC). It isabolished by ablation of the SC.3 Depth recordings have shown thatit arises in the superficial laminae of the visual cortex. Theproduction of a VEP component of such magnitude requires thesynchronous activity of a large number of neurones oriented in thesame plane.6 The cortex is probably the only such structure in theneonatal brain, and this large negative wave is completely absentfrom the VEPs of the holoprosencephalic infant with no OC. Theearly positive wave in the kitten can be recorded from the OCfollowing stimulation of the lateral geniculate nucleus (LGN); it isabolished by ablation of the LGN Depth recordings show that itarises from the deeper laminae of the visual cortex, which receive themain input from the LGN.5 Its development in the humancoincides with the development of basilar dendrites on neurones inthe deeper laminae of the OC,’ which, in the monkey, receive all ofthe input from the LGN.8The asymmetry noted in the VEP of the infant of 27 weeks’

gestation at 6 and 9 months involves the amplitudes of the shortlatency waves, suggesting damage to the input system.9 Similarasymmetry in short latency VEP components has been demon-strated, both at 40 weeks gestation and 9 months of age, in

48

association with areas of periventricular low density on the

computerised tomographic scan.9 The symmetry of the longerlatency negative wave at 40 days of age (ie, 33 weeks’ gestation) mayindicate that, as in the kitten, these inputs to the OC have a differentorigin.We suggest that a cortical origin of the two VEP components

discussed by Dubowitz et al is favoured by the evidence available,and that some of the evidence presented to the contrary may bedifferently interpreted.

Bristol Maternity Hospital,Bristol BS2 8EG

O. H. STANLEYP. J. FLEMINGM. H. MORGAN

1. Atkinson J. How does infant vision change in the first three months of life? In: PrechtlHFR, ed. Continuity of neural functions from prenatal to postnatal life. Clin DevMed 1985; 94: 159-78.

2. Wurtz RA, Albano JE. Visual-motor function of the primate superior colliculus. AnnRev Neurosci 1980; 3: 189-226.

3. Rose GH, Lindsley DB. Development of visually evoked potentials in kittens: specificand non-specific responses. J Neurophysiol 1968; 31: 607-23.

4. Stanley OH, Fleming PJ, Morgan HM. Analysis of maturational changes in thewaveform of the neonatal flash evoked potential. Electroenceph Clin Neurophysiolabstr (in press).

5. Kato N, Kawaguchi S, Yamamoto T, Samejima A, Miyata H. Postnatal developmentof the geniculocortical projection in the cat: electrophysiological and morphologicalstudies. Exp Brain Res 1983; 51: 65-72.

6. Cooper R, Winter AL, Crow HJ, Walter WG. Comparison of subcortiral, cortical andscalp activity using chronically indwelling electrodes in man. Electroenceph ClinNeurophysiol 1965; 18: 217-228.

7. Purpura DP. Developmental pathobiology of cortical neurones in immature humanbrain. In: Gluck LL, ed. Intrauterine asphyxia and the developing foetal brain.Chicago: Medical Year Book Publishers, 1977.

8. Rakic P. Developmental events leading to laminar and areal organisation of theneocortex. In: Schmitt FO, ed. The organisation of the cerebral cortex. Cambridge,Mass: MIT Press, 1981.

9. Kurtzberg D. Event-related potentials in the evaluation of high-risk infants. Proc NYAcad Sci 1984; 425: 300-18.

SIR,-In a 1984 paper on collicular vision in the newboml (andelsewhere) I described the early development of subcortical visualstructures in man. Also Maurer and Lewis2 reported that theretinogeniculostriate system functions in the second month of life,while the retinocollicular pathway functions at birth. Recent

experimental microelectrophysiological research has shown that thesuperior colliculus receives Y projections from the retina. Throughthe Y pathway the superior colliculus gets information that mightbriefly be described by the question: "Where is it?". After that thesuperior colliculus integrates motor behaviour and makes possiblethe tracking of the object. This rudimentary vision I called"collicular vision". Perhaps this rudimentary vision in the newborn(up to 2 months?) should be called "collicular or subcortical vision",a suggestion supported by Dr Dubowitz and her colleagues’findings.Paske Zjacica 54,59000 Sibenik, Yugoslavia ANTE STAMPALIJA

1. Stampalija A. Collicular vision m newborn infants: Neuroanatomical and clinicalstudy. Proceedings of Neuro-ophthalmology Congress, University of Antwerp.Antwerp, 1984: 297-300.

2. Maurer D, Lewis TL. Physiological explanation for the early visual development. RevCanad Psychol 1979; 33: 232-49.

SUBCUTANEOUS IMMUNOGLOBULIN HOMETREATMENT IN HYPOGAMMAGLOBULINAEMIA

SIR,-Dr Ochs and colleagues (March 15, p 610), evaluating theuse of home treatment with intravenous immunoglobulin (IVIG)for patients with hypogammaglobulinaemia, did not mention theequally effective and simple use of subcutaneous immunoglo-bulin.l,2 In Australasia human normal immunoglobulin (HNI;Commonwealth Serum Laboratories) prepared for intramuscularuse as a 16% solution has been shown to raise IgG levels to normaland to reduce the frequency of infections in such patients.3 This canbe accomplished by a weekly infusion into the subcutaneous tissues

of the anterior abdominal wall at a dose of 50 mg/kg, usually at a rateof 2-3 ml/h over about 6 h via a portable infusion pump and scalpvein needle. This can safely be done overnight by the patient, whomay have had as little as an hour of instruction in the technique. Theonly side-effect is mild transient discomfort at the infusion site. Thistechnique of drug administration has been used successfully forseveral years in children with thalassaemia major requiringdesferrioxamine infusions.The initial outlay for a portable infusion pump is offset by the use

of the intramuscular preparation rather than the more expensiveintravenous preparation, also prepared by the CommonwealthSerum Laboratories. These two preparations cost the Australiantaxpayer$A3’75 and$A9.00/g, respectively. Intravenous infusionsets and fluids add further to the cost of treatment with IVIG. Thuson grounds of convenience and expense home treatment withsubcutaneously administered immunoglobulin may have advan-tages over the intravenous route.

Royal Perth Hospital,Perth, Western Australia 6000 MICHAEL F. LEAHY

1. Berger M, Cupps TR, Fanci AS. Immunoglobulin replacement therapy by slowsubcutaneous infusion. Ann Intern Med 1980; 93: 55.

2. Roord JJ, van der Meer JWM, Kuis W, et al. Home treatment in patients withantibody deficiency by slow subcutaneous infusion of gammaglobulin. Lancet1982; i: 689-90.

3. Bayston K, Leahy MF, McCreanor JD, Gebbie T. Subcutaneous gammaglobulin:effective management of hypogammaglobulinaemia NZ Med J 1985; 98: 652.

CIPROFLOXACIN AND ANTACIDS

SiR,—Using oral ciprofloxacin for infections due to Pseudomonasaeruginosa, Scully et all reported rates of 77% for clinical response,34% for bacteriological cure, and 26% for development ofresistance among Ps aeruginosa isolates. Most patients had severeunderlying disorders and many were seriously ill. Mean peak/trough ciprofloxacin serum levels (mg/1) were 2-9/0-54 after 500 mgand 3-6/1-0 after 750 mg. Scully et al did not indicate whetherpatients were receiving antacids.We used ciprofloxacin 500 mg orally twice daily for 7 days in

complicated urinary-tract infections in 20 elderly patients (meanage 71) 11 of whom had Ps aeruginosa infections. Mean ciprofloxa-cin serum levels were lower (p < 0-05, Wilcoxon rank sum) in thoseon frequent antacid therapy:

Day Serum ciprofloxacin (mgll): meantSDOn antacids Not on antacids

1 (peak) 0-82 &plusmn;0-65 2 &plusmn;0-971 (trough) 0.32&plusmn;0.13 11 &plusmn;0-66

3 (peak) 0.88&plusmn;0.89 2.6&plusmn;0.94

3 (trough) 0.38 &plusmn; 0.33 1.1 &plusmn; 0.63

At 1 week post-therapy 3/11 patients with Ps aeruginosa infectionhad relapsed. 1 had received antacids, and his Ps aeruginosa becameresistant to gentamicin and cefotaxime by macro-scale brothsusceptibility testing. Minimum inhibitory concentration rose

fourfold but remained in the susceptible range for ciprofloxacin,tobramycin, amikacin, and imipenem.

Antacids containing magnesium and aluminium reduce serumand urine levels of ciprofloxacin in healthy volunteers.2 Themechanism is probably reduced absorption due to formation ofdrug-cationic chelate complexes. Concomitant antacid therapy mayinterfere with ciprofloxacin efficacy for treatment of infections dueto Ps aeruginosa or other organisms.

Infectious Diseases Section,Creighton University School of Medicine,VA Medical Center,Omaha, Nebraska 68105, USA

L. C. PREHEIMT. A. CUEVAS

J. S. ROCCAFORTEM. A. MELLENCAMPM. J. BITTNER

1. Scully BE, Neu HC, Parry MF, Mandell W. Oral ciprofloxacin therapy of infectionsdue to Pseudomonas aeruginosa. Lancet 1986; i: 819-22.

2. Hoffken G, Borner K, Glatzel PD, Koeppe P, Lode H. Reduced enteral absorption ofciprofloxacin in the presence of antacids. Eur J Clin Microbiol 1985; 4: 345.