MUSIC CLINICS

147

Letters to the Editor ERYTHROMYCIN FOR PERTUSSIS: PROBABLE REASONS FOR PAST FAILURES

SiR,-Pertussis organisms

are

eradicated if

patients

with

whooping cough are treated with antimicrobial agents active against Bordetella pertussis, provided that the drug diffuses in significant concentrations into respiratory tract secretions. Several drugs can dependably achieve early "bacteriological cure"; however, the clinical course of illness is not altered if treatment is delayed until the paroxysmal stage, which is when the diagnosis is most often first suspected.l-3 These drugs may be effective in prophylaxis of exposed susceptible individuals or in aborting or attenuating the disease if administered before paroxysmal stage. 1,4 Their administration to patients at any stage of pertussis may render them non-infectious. Erythromycin is the most effective drug for this purpose, and it is the least toxic. In some studies erythromycin has failed to eradicate pertussis organisms from patients with pertussis or there has been bacteriological relapse after treatment stops.5-9 One infant with such a relapse was contagious.5I have warned that bacteriological relapse occurs in about 10% of patients given courses of only 7-10 days of erythromycin therapy, but I have never seen, and to my knowledge there is no report of, a patient having a bacteriological relapse after treatment for 14 days.1,10,11 The longer course either regularly eliminates the organism or suppresses growth until specific secretory immunoglobulin develops, inhibiting relapse when the drug is discontinued. This does not explain the delay or failure of erythromycin to eradicate pertussis organisms from some patients after up to 10 days of therapy. Although sensitivity testing in these rare treatment failures was not reported, its resistance to erythromycin is unlikely. We found erythromycin to be the most active of nine antimicrobial drugs studied in vitro against 36 strains of B pertussis isolated from patients from several North American cities.12 All strains were very sensitive, with a mean minimal inhibitory concentration (MIC) of 0 - 29 (range 0 - 02-1 - 56) ).lg/ml and a mean minimal bactericidal concentration (MBC) of 0 - 50 (range 0-04 to 1-56) g/ml. To my knowledge, there has been no report of in-vitro resistance of B pertussis to this drug or reports of other drugs showing greater activity in vitro than erythromycin. What, then, is the explanation for the erythromycin failures? A comparison of the reports of erythromycin failure with those showing good results for both eradication and prophylaxis of pertussis organisms reveals one consistent difference. The used when the outcome was good was the erythromycin estolate while treatment in the reports showing delay or failure in eradication or apparent failure of prophylaxis was with the ethylsuccinate5-7 or stearate esters,8,9 which produce significantly lower serum levels of erythromycin when given at the same recommended daily dosage of 30-50 mg/kg. In our study of erythromycin concentrations in serum and middle-ear effusions in children treated with erythromycin estolate or ethylsuccinate for acute otitis media 13 the serum to effusion ratios were similar (1-81 and 1 - 56, respectively), as might be expected since drug levels in these fluids reflect free erythromycin base, which should have the same diffusion properties in both circumstances. However, the serum and effusion concentrations achieved in patients given the estolate ester were several times higher than they were in those who received the ethylsuccinate ester. The mean level of 4 -18 g/ml of erythromycin achieved in the middle-ear effusions of children treated with the estolate ester was several times greater than the MIC and MBC we observed for all 36 strains of B pertussis. Further, the lowest level of erythromycin achieved in effusions of patients who received the estolate was significantly above the MIC and MBC of all 36 strains. In contrast, several of the 36 strains were not killed or inhibited by the mean erythromycin effusion concentration of 0’ 84 pg/ml that was achieved in patients who received the

ester,preparation

ethylsuccinate ester. I conclude that these observations adequately explain the conflict-

ing results of reports on the efficacy of erythromycin in the management of patients with pertussis and attempts at prophylaxis

using this drug. I strongly recommend the use of the estolate ester be utilised (or a treatment regimen that can be relied upon to produce comparable blood levels) in a daily dosage at 50 mg/kg for 14 days. Controlled studies substantiating the efficacy of erythromycin for prophylaxis of exposed susceptible contacts and in curbing outbreaks of the disease are needed. The design of such studies should take the above observations into considerations. Departments of Pediatrics, Tripler Army Medical Center and School of Medicine,

University of Hawaii,

JAMES W. BASS

Honolulu, Hawaii, USA

1 Bass JW, Klenk EL, Kotheimer JB, Linnemann CC, Smith MHD, Mitchell IA, Coner EJ, Leiderman DS Antimicrobial treatment of pertussis. J Pediatr 1969, 75: 768-81 2 Islur J, Anglin CS, Middleton PJ. The whooping cough syndrome- a continuing problem. Clin Pediatr 1975; 14: 171-76 3. Baraff LJ, Wilkins J, Wehrle PF The role of antibiotics, immunizations, and adenoviruses in pertussis Pediatrics 1978; 61: 224-30 4. Altemeier WA, Ayoub EM Erythromycin prophylaxis for pertussis Pediatrics 1977, 59: 623-25 5 Halsey NA, Welling MA, Lehman RM Nosocomial pertussis, a failure or erythromycin treatment and prophylaxis Am J Dis Child 1980; 134: 521-22 6 Grob PR. Prophylactic erythromycin for whooping cough contacts Lancet 1981; i 772. 7. Spencely M, Lambert HP. Prophylactic erythromycin for whooping cough contacts Lancet 1981, i 772-73 8 Henry RL, Dorman DC, Skinner JA, Mellis CM Antimicrobial therapy in whooping cough. Med J Aust 1981, ii 27-28 9 Henry RL, Dorman DC, Skinner JA, Mellis CM. Limitations of erythromycin in whooping cough Med J Aust 1981, ii 108-09. 10 Bass JW, Harden LB. Treatment and prophylaxis failure of erythromycin in pertussis. Am J Dis Child 1980; 134: 1178-79 11 Bass JW Use of erythromycin in pertussis outbreaks Pediatrics 1983, 72: 748-49 12. Bass JW, Crast FW Kotheimer JB, Mitchell IA Susceptibility of Bordetella pertussis to nine antimicrobial agents. Am J Dis Child 1969, 117: 276-80 13. Bass JW, Steele RW, Wiebe RA, Dierdorff Erythromycin concentrations in middle ear exudates Pediatrics 1971, 48: 417-22

MUSIC CLINICS

SIR,-Your June 8 editorial draws attention to the occupational disorders of performing musicians. These have been studied in several centres, including our own since 1979, and case histories in the lay press recently of two concert pianists (Leon Fleischer and Gary Graffmann) highlight problems and solutions. Success in treatment is aided by several factors: (1) neurological skills associated with knowledge of the techniques of musical performance, (2) detailed observation of the patient playing his or her musical ’instrument; (3) documentation of the patient’s psychophysiological profile (baseline monitoring of fingertip skin temperature and electromyographic [EMG] biofeedback both at rest and with physiological and/or psychological stressors in addition to routine diagnostic tests such as X-rays, EMG, and nerve conduction. velocities); and (4) willingness on the part of the physician to explore new avenues and to plan an individual treatment programme with the musician-patient. Symptoms are multifactorialland analysis of the disorders invites the cooperation of music teachers at all stages. We have concentrated on pianists and string players, since symptoms in wind players demand specific knowledge of lip problems and pulmonary physiology. The string players are nearly all professional orchestral or chamber music players, and anxiety may interfere with performance in ensemble playing (often through the fast tempi

required by conductors). The neurological diagnoses include tendonitis, myalgia, muscle spasm, "myofascial syndrome", cervical spondylosis, sympathetic reflex dystrophy, bruxism, and median nerve compression in the carpal tunnel. Pianists tend to have more symptoms in the right hand and upper limb, and violin and viola players in the left hand and upper limb and the neck (because of the unphysiological posture during playing). One of our pianists (aged 54) had reflex spasms of the right thumb and index (classifiable as a tic3or focal dystonia) for 20 years, occurring at rest and increased with piano playing. These almost disappeared with EMG biofeedback training and he showed a 9007o reduction in EMG microvolt readings, indicating lessening of muscle tension at rest and during activity; he returned to professional playing and remains well on a 2’/z-year follow-up.

148 Minor

injuries may precipitate symptoms, and

one of our early 30-year-old viola player with sympathetic reflex dystrophy following tennis elbow (lateral epicondylitis). This patient had been disabled for 14 months, not responding to several therapies, including eleven sympathetic nerve blocks. Complete cases

was

a

recovery followed training with thermal biofeedback: she learned to raise the skin temperature of her fingers from 22-1°C to a physiological 32-1°C. She returned to full professional life and remains well on a 5-year follow-up. Details of treatment are described in our Textbook of Biological Feedback4and in a 1984 report.5 Twenty selected patients responded to various modalities of biofeedback. Our patients learn voluntary control of skin temperature and motor self-regulations; they learn to scan the entire body for muscle tone (tension) and to keep muscle tone at appropriate levels. They learn to shift their focus of attention rapidly and comfortably. Conscientious home practice for biofeedback is emphasised. We also record skin conductance, but we are not using this modality for feedback learning. Six patients improved well with median nerve decompression, physical therapy, muscle re-education, and appropriate modification of posture and work habits. Interesting research questions arise, such as the role of the cerebellum in motor 6 learning, in kinaesthetic memory, and in conditioning. A musician’s medical survey is being collected by the International Conference of Symphony and Opera Musicians, and we hope thus to gather further information. Many aspects are being addressed, such as the widespread use of beta blockers by players during performance, the effects of poor lighting and cramped conditions in orchestral pits, and harmful decibel levels of sound for players seated just in front of the brass section. Prevention of these occupational disorders is obviously the next logical step. With the cooperation of the administration of a major orchestra, we are preparing courses for players, so that musicians may gain more conscious appreciation of the cerebral surveillance that their motor and sensory discipline requires in order to express non-verbal emotions through music. 324 E W lsconsm

Avenue,

Suite 6433, Milwaukee, Wisconsin 53202, USA

M. FISCHER-WILLIAMS

Henson RA, eds. Music and the brain. Studies in the neurology of music. London. William Heinemann Medical Books, 1977. McLaughlin T. Music and communications. New York. St Martin’s Press, 1970. Brain WR, Walton JN. Brain’s diseases of the nervous system, 7th ed. London: Oxford University Press, 1969 137 Fischer-Williams M, Nigl AJ, Sovine DL. A textbook of biological feedback. New York: Human Sciences Press, 1981. Fischer-Williams M, Sovine DL Clifford B. Musicians with occupational hand disorders treated by biofeedback, Proceedings of 15th annual meeting of the Biofeedback Society of America, 1984. Gellman RS, Miles FA. A new role for the cerebellum in conditioning? Trends in Neurosci 1985, 8: 181-82

1 Critchley M, 2 3. 4 5

6.

MENINGORADICULITIS ASSOCIATED WITH INFECTIONS BY BORRELIA BURGDORFERI

SIR,-Dr Weill and colleagues (June 15,

p 1400) reported two of meningoradiculitis due to Borrelia burgdorferi in France. We have seen two similar cases, suggesting that the neurological abnormalities of Lyme disease may be a common finding in France if antibody to B burgdorferi is systematically looked for in such cases

patients. A 61-year-old woman was bitten by an "insect" on the left thigh in a forest near Paris, in July, 1984. 2 weeks later, excruciating backache and a motor and sensory radiculopathy developed in her left leg (femoral nerve). 1 month later, bilateral facial palsy and a right motor and sensory radiculopathy (femoral nerve) developed. Her cerebrospinal fluid contained 476 leucocytes/1 (100% lymphocytes) and protein 0-87 g/l. She was treated with intravenous penicillin G (24 million units/day in divided doses) from Sept 14 to Oct 3, 1984, and then with oral penicillin for 5 months. By the second day the severe backache and the pain in the lower limbs were much improved and they disappeared within a week. By the second week, the bilateral facial palsy and lower limbs weakness began to subside and had disappeared by the second month, except for the left facial palsy which took 6 months to

resolve.

Specific IgG antibody titres against B burgdorferi were 20

(Sept 27, 1984) and 80 (Jan 30, 1985). Antibody titres were assayed in Prof Edlinger’s laboratory at 1’ Institut Pasteur, Paris; the American B31 strain, kindly provided by Dr Taylor, Texas Health was used. IgG titres in normal controls are less than 20. A 28-year-old man was bitten by an "insect" on the left thigh, ina forest near Paris, in June 1984. Over the next 7 days, erythema chronicum migrans developed near the site of the bite; it resolved over the ensuing 3 weeks. 10 days later neurological abnormalities developed: backache, left lower limb pain, emotional lability, and, finally, bilateral facial palsy. The cerebrospinal fluid contained 110 Ieucocytes/1 (90% lymphocytes) and protein 12g/1. He was treated with intravenous penicillin G (30 million units/day in divided doses) for 1 month. All clinical symptoms progressively disappeared within 4 months. Specific IgG antibody titres against B burgdorferi were 40 (Nov 6, 1984) and 80 (March 20, 1985). These two patients with lymphocytic meningoradiculitis had raised antibody titres against an American B burgdorferi strain, suggesting that a related or identical organism is the causative agent of neurological abnormalities of the "Lyme complex" in France. 1-3 These findings also suggest that in Europe, as in the USA, specific serological studies to B burgdorferi may be especially helpful in the diagnostic laboratory work-up of patients with atypical neurological abnormalities or oligoarthritis of unknown origin. 1,4,5 In our two patients, high-dose intravenous penicillininduced a dramatic (case 1) or progressive (case 2) clinical improvement. Because of the low yield of culture 1,7 and the delay in the specific antibody response, 1,4 lymphocytic meningoradiculitis consistent with the diagnosis of Lyme disease should be treated with high-dose intravenous penicillin as early as possible, even before the rise in specific antibody titres.

Center,

of Rheumatology, Hôpital Cochin,

Department 75014

Paris, France

ANDRE KAHAN

Medical Service II, Centre Hospitalier Général, Senlis

MICHEL RUEL

Department of Rheumatology, Hôpital Cochin, Paris

ANNE MAYOUX BENHAMOU BERNARD AMOR

1. Steere

AC, Grodzicki RL, Kornblatt AN, et al. The spirochetal etiology of Lyme disease N Engl J Med 1983; 308: 733-40. 2 Kahan A, Dougados M, Vannier A, Amor B Spirochaetal aetiology for Lyme disease Lancet 1983; ii: 174 3. Wilske B, Preac Mursic 4.

V, Schierz G. Antigenic heterogeneity of European Borreha burgdorferi strains isolated from patients and ticks. Lancet 1985; i: 1099. Shrestha M, Grodzicki RL, Steere AC. Diagnosing early Lyme disease. Am J Med

1985; 78: 235-40 5. Reik L, Steere AC, Bartenhagen NH, Shope RE, Malawista SE. Neurologic abnormalities of Lyme disease Medicine (Baltimore) 1979; 58: 281-94 6. Steere AC, Pachner AR, Malawista SE. Neurologic abnormalities of Lyme disease. Successful treatment with high-dose intravenous penicillin. Ann Intern Med 1983; 99: 767-72. 7. Benach JL, Bosler EM, Hanrahan JP, et al. Spirochetes isolated from the blood of two patients with Lyme disease N Engl J Med 1983; 308: 740-42.

CYCLO-OXYGENASE AND LIPO-OXYGENASE INHIBITORS MAY SUBSTITUTE FOR STEROID TREATMENT IN BRAIN OEDEMA an important complication both of brain and of radiotherapy to the brain. Conservative treatment of brain oedema usually consists of steroid therapy, though barbiturates also alleviate central nervous system oedema. Nonsteroidal anti-inflammatory agents have been explored as well, with variable results.I-4 Most of these are cyclo-oxygenase inhibitors, which decrease prostaglandin and thromboxane synthesis. However, inhibitors of cyclo-oxygenase may push the process into the lipo-oxygenase pathway, resulting in more leukotriene synthesis,5-7 and leukotrienes may contribute to brain oedema as much as some of the prostaglandins do. We have explored an inhibitor of both cyclo-oxygenase and lipo-oxygenase (sodium meclofenamate) in a primate model and found significant reduction in radiation-induced brain oedema.Patients with brain oedema often respond to steroids but at the risk of dependency,which may eventually result in severe steroid toxicity. In a few patients we have

SIR,-Brain oedema is

tumours