EFFECT OF PARENTAL SMOKING ON IgE LEVELS IN CHILDREN

993

and sedating effects, though further studies are necessary to confirm dose threshold effect. this and Withdrawal scores were not suppressed to zero and increasing the lofexidine dose to suppress all opiate withdrawal signs and symptoms may produce hypotension and sedation. Nevertheless the demonstration of striking anti-withdrawal efficacy in chronic methadone addicts suggests that in lofexidine we may have a further new treatment for opiate detoxification and for the transition fromopiate dependence to drug-free or naltrexone maintenance. to

establish whether it is

Research Facilities, Fair Oaks Hospital,

Summit, New

Jersey, 07901, U.S.A.;

and Addiction-Prevention Treatment Foundation and Substance Abuse Unit,

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut

a

MARK S. GOLD A. CARTER POTTASH WILLIAM J. ANNITTO IRL EXTEIN HERBERT D. KLEBER

DIFFUSE EXERCISE-INDUCED MUSCLE PAIN OF UNDETERMINED CAUSE RELIEVED BY VERAPAMIL

SIR,-A 35-year-old man was admitted to this neurological centre June 9, 1980. In his late twenties he had first experienced dull painful aching in the calf and thigh muscles, coming on after on

prolonged exertion and generally towards the end of the day. If he rested, the pain would disappear over a few hours, and pain was invariably relieved by a night’s sleep, however prolonged and intense the preceding exertion. Gradually, however, the muscular aching increased and spread, after 3 years, to the thighs, buttocks, and hamstrings and then to the arms, hands, and shoulder girdle muscles. In time the pain became almost constant with only slight relief resulting from rest. His sister, who was 4 years older, had had identical symptoms for the previous 12 years. The patient and his sister were the only children of unrelated, healthy parents and there was no family history of any similar symptoms. The patient was not taking drugs and had no history of drug abuse or excessive alcohol intake. The cardiovascular and respiratory systems and the abdomen seemed normal-as, indeed, did the neuromuscular system on examination. The configuration of the skeletal muscles was normal, they were not tender, and there was no myotonia, no fasciculation, and no myoidema. The consistency of the muscles on palpation appeared normal. Direct myotatic irritability and the tendon reflexes were also normal, and indeed no physical abnormality could be identified. The patient had been extensively investigated in London at Guy’s Hospital and the National Hospital, but was reinvestigated because, by the time he came to Newcastle, his disabling muscle pain was interfering with his ability to work. The many tests did not point to a diagnosis. The following results, for example, were normal: blood lactate rise after ischaemic work; electromyography and nerve conduction velocities including singlefibre electromyography; muscle histology and histochemistry; total muscle glycogen, AMP deaminase (1-06 mol/min/mg protein), carnitine palmityl transferase (25nmol/min/mg of non-collagen protein [NCP]), muscle creatine kinase (11.66 IU/mg NCP), and adenylic kinase (0-427 mol/min/mg NCP); free and total muscle carnitine values (16 -7 and 19.6 6 nmol/mg NCP). Even after prolonged exercise, myoglobinuria could not be detected. .Bùtochondrial function (Dr John Morgan-Hughes, National Hospital) was normal. Electron microscopy of muscle biopsy sections here in Newcastle also showed no morphological abnormality; the mitochondria were normal in size and shape and no tubular aggregates were found. This patient’s condition and that of his sister thus remained unexplained. We have now seen many such patients with symptoms resembling those of McArdle’s disease but in whom we have been .mable to identify a cause. We were satisfied that there was no psychological cause for his symptoms and that he had an

unexplained metabolic myopathy. Many drugs had been tried before he came to Newcastle, and we suggested an empirical trial of others. Powerful analgesics produced some temporary and partial relief, but diazepam, phenytoin, procaine amide, beta-adrenergic "’locking agents, carbamazepine, and many more drugs were

unhelpful. Dantrolene sodium slightly improved the pain, but it also produced substantial muscle weakness and had to be discontinued. Although there was no histological or other evidence of ischaemia of his skeletal muscles, Dr M. B. Holmes decided upon a trial of naftidrofuryl oxalate 100 mg three times daily. Within 48 hours both the patient and his sister found that their muscular pain was greatly increased, and they were confined to bed. After withdrawal of this drug their condition returned to what it had been before, again over 48 hours. Since one effect of the latter drug is to increase intramuscular ATP and to enhance cellular oxidative activity, it seemed reasonable to try verapamil hydrochloride, which reduces the turnover of high-energy phosphates in cardiac muscle and probably in skeletal muscle as well, inhibits movement of calcium across the muscle cell membrane, and decreases muscular requirement for oxygen and the activity of calcium-dependent ATPase. It has been suggested that such an effect of the calcium inhibitor class of drugs might reduce muscle fibre necrosis in degenerative and inflammatory myopathies. Despite the fact that there was no evidence clinically or histologically of muscle fibre necrosis in this case which might be calcium-induced, I suggested to Dr Holmes that he treat the patient with verapamil 60 mg three times daily. The response was immediate and dramatic with remarkable relief of his muscle pain and tenderness within 36 hours, and his sister has been similarly helped. The patient’s dose was increased to 120 mg three times daily with total relief, but at this dose his sister had tachycardia and extrasystoles and the dose was reduced to 60 mg four times daily without any return of muscle pain. Improvement has been sustained in both patients for several weeks. One suggestion (from Prof. J. B. Harris) is that excessive calcium load upon the muscle mitochondria accounted for the pain and that this has been reduced by the verapamil. I would be interested to hear from colleagues who may have some explanation for this remarkable response which must, of course, be confirmed by further trials in similar cases. I thank the patient’s general practitioner, Dr M. B. Holmes of St Brelade’s, Jersey; Dr R. C. Hughes (Guy’s Hospital); and Dr John Morgan-Hughes (National Hospital) for access to reports of investigations done when the

patient was under their care. Regional Neurological Centre, General Hospital, Newcastle upon Tyne NE4 6BE; and Department of Neurology, University of Newcastle upon Tyne

EFFECT OF PARENTAL SMOKING ON CHILDREN

JOHN WALTON IgE LEVELS IN

SIR,-While studying the development of atopic disease in highrisk families’ (where both parents have atopic disease) we looked at the effect of parental smoking on the development of serum IgE levels in 46 children from 0 to 3 years of age. The smoking habits of the parents were assessed by questionnaire when the children were 3, 6, 9, 12, 18, and 36 months of age, and the children were divided into two groups, according to the answers, as coming from non-smoking homes or smoking homes. All the children were given a clinical examination and blood was sampled at most visits. Serum IgE levels were determined using Phadebas ’PRIEST’2on serum kept at -20°C pending analysis. The IgE level rose more rapidly in children from smoking families (figure) and a significant group difference (p<0-05) was seen at 9 and 36 months of age. The scatter of the IgE levels was considerable, which probably explains the lack of significance at 12 and 18 months. This finding accords with recent findings in smoking/nonsmoking adults3 and adds further evidence to the negative effects of Kjellman N-IM, Johansson SGO. Soy versus cow’s milk in infants with a biparental history ofatopic disease: Development of atopic disease and immunoglobulins from birth to 4 years of age Clin Allergy 1979; 9: 347-58. 2. Ceska M, Lundkvist U. A new and simple radioimmunoassay method for the determination of IgE. Immunochemistry 1972; 9: 1021-30. 3. Gerrard JW, Heiner DC, Ko CG, Mink J, Meyers A, Dosman JA. Immunoglobulin levels in smokers and non-smokers. Ann Allergy 1980; 44: 261-62. 1

994

Bacteria-free, non-pneumonic zone (within circle) around a large radiating microcolony of aspergilli in lung of patient who died of legionnaires’ disease. Serum IgE levels in children from families.

smoking

and

non-smoking

passive smoking.4-6 The smoke may facilitate sensitisation by making the penetration through the mucous membrane easier for allergens or by acting directly on T-cells. The effect on the production of specific antibodies in these children is currently being investigated. Department of Paediatrics, University Hospital, S-58185 Linköping, Sweden

N.-I. MAX KJELLMAN

IN VIVO INHIBITION OF LEGIONELLA PNEUMOPHILA BY ASPERGILLUS

SiR,—Since its recognition in 1976 legionnaires’ disease (LD) has been frequently reported in patients with medical conditions,7-10 and in our experience the infecting bacterium may coexist with other infectious agents such as viruses, other bacteria, and fungi. We have studied three cases of fatal pneumonia caused by Legionella pneumophila serogroup 1 in which there was severe, coexisting pulmonary aspergillosis proved by direct immunofluorescence staining.11 In lung sections from all three patients LD bacteria were absent from areas contiguous to large, radiating microcolonies of Aspergillus hyphae (figure). In

pneumonia underlying

4. Cameron P, Kostin J, Zaks JM, Wolfe JH, Tighe G, Oselett B, Stocker R, Winton J. The health of smokers’ and nonsmokers’ children. J Allergy 1969; 43: 336-41. 5. Shephard RJ, Ponsford E, LaBarre R, Basu PK. Effect of cigarette smoke on the eyes and airway. Int Arch Occup Environ Health 1979; 43: 135-44. 6. Harlap S, Davies AM. Infant admissions to hospital and maternal smoking. Lancet 1974; i: 529-32. 7. Tobin J, Mitchell RG, Legionnaires’ disease in a transplant unit. Commun Dis Rep 79/43. London: Communicable Disease Surveillance Centre, 1979. 8. Frenkel JK, Baker LH, Chonko AM. Autopsy diagnosis of Legionnaires’ disease in immunosuppressed patients: a paleodiagnosis using Giemsa stain (Wohlbach modification) Ann Intern Med 1979; 90: 559-62. 9. Gump DW, Frank RO, Winn WC, Jr, Foster RS, Jr, Broom CV, Cherry WB. Legionnaires’ disease m patients with associated serious disease. Ann Intern Med

1979; 90: 538-42. LD, Burch KH, Fisher E, Madhavan T, Kiani D, Neblett T, Quinn EL The compromised host and legionnaires’ disease. Ann Intern Med 1979; 90:

10. Saravolatz

533-37. 11. Chandler FW, Kaplan W, Ajello L. Immunofluorescence diagnosis-current status. In: Colour atlas and textbook of the histopathology of mycotic diseases. London: Wolfe Medical Publications, 1980: 23-54.

(Gomori x 7).

methenamine silver with

haematoxylin

and eosin

counterstam:

general, the greater the number of aspergilli per unit area, the wider the surrounding zones of inhibition. In the absence of the bacterium, few inflammatory cells were seen in these zones, and when present, they were usually sparse and well preserved. The bacteria-free, non-pneumonic zone surrounding a large fungal mass usually covered the width of two to six alveoli, and this pattern of inhibition was striking on low power examination (figure). When an individual Aspergillus hypha, or small groups of them, were seen in areas of pulmonary consolidation, contiguous bacterial growth was not inhibited. In these patients, it therefore appeared that only large numbers of compact aspergilli inhibited the growth of L.

pneumophila. Two possible mechanisms for this inhibition are suggested. First, there may be competition for nutrients. Second, large numbers of aspergilli might contain sufficient amounts of substances that move into surrounding lung tissue and act as growth inhibitors of L. 12 pneumophila. Certain Aspergillus species do produce antibiotics. In lung sections from two other patients with confirmed LD pneumonia complicated by severe infection with Candida sp., growth of L. pneumophila contiguous to large numbers of these fungi was not inhibited. The relevance of these in vivo observations to the possible development of antibiotics against L. pneumophila and other Legionella spp. from certain of the Aspergillus spp. is not known. However, in vitro inhibition studies with cell-free components of selected aspergilli are underway. Pathology Division, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia 30333, U.S.A.

FRANCIS W. CHANDLER

ADJUVANT CHEMOTHERAPY FOR BREAST CANCER SIR,-Your April 4 editorial may do more than justice to the published results of Bonadonna and Valagussa. You refer to their claim to have demonstrated significant improvement in disease-free survival in patients who received 85% or more of the cyclophosphamide/methotrexate/5-fluorouracil dose planned. However, when 12.

Korzybski T, Kowszyk-Gindifer Z, Kurylowicz W. Antibiotics: Origin, nature and properties. Washingtonm DC: American Society for Microbiology, 197 8:1813-61