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GEMFIBROZIL-INDUCED HEADACHE
1246 CAMYLOFIN INTOXICATION REVERSED BY NALOXONE
SIR,-Camylofin is a smooth-muscle relaxant used as an antispasmodic. In Brazil the proprietary name is ’EspasmoSilidron’ ; it contains 20 mg camylofm plus 40 mg dimethicone per 0-6 ml. In Europe and South Africa the proprietary name is ’Avacan’. A 30-day-old baby weighing 5-4 kg had increased bowel movements and abdominal cramps. His mother twice gave him 7 drops of espasmo-silidron (about 10 mg camylofm or 1-75 mg/kg). After the second dose the baby became pale, hypoactive, and cyanosed. Upon admission 6 h later, he was in deep coma with bilateral pinpoint pupils and respiratory depression requiring mechanical ventilation. Intravenous naloxone 0-02 mg/kg immediately reversed the clinical picture. 0-02 mg/kg doses had to be administered four more times in the next 16 h. The baby was discharged 3 days later. A 2-day-old baby weighing 4-0 kg was given 20 drops of espasmo-silidron twice, 30 min apart (a total of about 26 mg camylofm or 6-5 mg/kg) because of suspected colic. About 90 min later she was found with a very slow respiratory rate, cyanosis, and hypotonia, and was admitted unconscious to hospital, with bilateral pinpoint pupils, bradycardia, and intermittent apnoea requiring mechanical ventilation. Intravenous naloxone 0-02 mg/kg reversed the picture within minutes. An additional 0-02 mg/kg dose was needed 8 h after the first. The baby was discharged after 4 days. Camylofin is an antispasmodic of atropine-like and papaverinelike action. Side-effects in clinical use are thought to be negligible. However, it seems that ingestion of excessive amounts by infants produces symptoms of opioid intoxication. The good results obtained with naloxone, a pure opioid antagonist, support this. Even though the first naloxone dose led rapidly to improvement, several additional doses were necessary in one baby, as happens in other types of opioid intoxication.
As in the case presented by Arellano et al, the headaches started week after re-exposure to gemfibrozil and each intake precipitated a new episode 45-60 min later. The short half-life of gemfibrozil (1-5h) indicates that the headache was not related to reaching a steady-state (four to five times the half-life during continuous adminstration). The lowering of very-low-density lipoproteins by gemfibrozil takes 2-5 days, and reaches a peak 4 weeks later.2 We do not know how the lowering of plasma lipids might cause headache. one
JOSÉ ALVAREZ-SABIN Department of Neurology and Clinical Pharmacology, Hospital de la C S Vall d’Hebron, 08035 Barcelona, Spain
AGUSTIN CODINA CARLOS RODRÍGUEZ JOAN-RAMON LAPORTE
1. Arellano F, Dé Cos M, Valiente R, Quirós C Gemfibrozil-induced headache Lancet 1988; i: 705. 2 Illinworth DR. Lipid-lowering drugs an overview of indications and optimum
therapeutic use Drugs 1987, 33: 259-79.
NON-INVASIVE SAMPLING METHOD FOR DETECTING CHLAMYDIA TRACHOMATIS
SIR,—The establishment of Chlamydia trachomatzs as a major pathogen of the genital tract has led to an increased awareness of its role in pelvic inflammatory disease1.2 and infertility34 in the untreated female. The economic cost of investigating and treating the resultant infertility must be considerable; and the psychological cost alone in these women is often devastating. Awareness of the pathogenicity of C trachomatis has led to an increasing demand for screening, primarily, although not exclusively, in females attending genitourinary medicine clinics.5 Screening policies vary considerably in the UK. In our clinic all females are screened for C trachomatis, and positive women and their consorts are treated. All male clinic attenders with symptoms treated empirically. This policy has not controlled heterosexual transmission or the systemic infections arising from cervical infection since male patients have not always held their urine for the recommended three hours before urethral sampling for C trachomatis. There are also difficulties in recalling patients for an early morning slide to exclude urethritis. Nor does this policy make allowance for the recognition of the asymptomatic carriage of C trachomatis in the male urethra. We have done a study of all male patients attending our clinic for the first time, to evaluate the asymptomatic carriage of C trachomatis. This group would not normally be screened or treated for C trachomatis infection unless there were epidemiological grounds for doing so. We also wanted to evaluate the efficacy of early morning urine samples as a screening test. Patients were asked to collect an early morning sample, and on attendance at the clinic a urethral swab was taken, with a full clinical history. Swabs and urine were assayed for C trachomatis by an amplified ELISA (Boots-Celltech), and results on all urine samples are being confirmed by direct immunofluorescence (Syva ’Microtrak’), which we find better than cell culture for urine are
Department of Paediatrics, Instituto da Criança, Medical School, University of São Paulo, 05403 São Paulo
SP, Brazil
SAMUEL SCHVARTSMAN CLÁUDIO SCHVARTSMAN CLÁUDIO BARSANTI
AVAILABILITY OF ETHER
SIR,-Dr Bohmer and Dr Grounds (Oct 29, p 1022) ask whether anaesthetic ether may one day be unavailable. May & Baker are manufacturers of anaesthetic ether which, as Bohmer and Grounds point out, no longer has a product licence in the UK. It is, however, made available in the UK under sections 9 and 23 of the Medicines Act for individual patient treatment when there are very special circumstances. It is also available for export. There is no intention that anaesthetic ether should become unavailable and we are committed to continued manufacture. May & Baker Pharmaceuticals, Rhône-Poulenc Limited,
Dagenham, Essex RM10 7XS
J. O’GRADY
GEMFIBROZIL-INDUCED HEADACHE all described a patient with gemfibrozilinduced headache. We report another case. A 49-year-old man with hyperlipidaemia (type IV) had been treated with gemfibrozil 600 mg twice a day. After 4 weeks he had a holocephalic pulsatile headache of moderate intensity and frontotemporal predominance, a dry mouth, and slightly blurred vision. No neurological focal deficits, meningeal signs or papilloedema or other signs of intracranial hypertension were found. Computerised cranial tomography and lumbar puncture revealed no abnormality. His symptoms always appeared 45-60 min after taking gemfibrozil, receded after treatment with dipyrone or paracetamol, and reappeared after the night-time dose of gemfibrozil. After the drug was withdrawn, the patient had no more headaches. 4 weeks later gemfibrozil was re-started with the same regimen. After 7 symptom-free days, the same clinical picture occurred. At present (Oct 18, 1988) the patient has not taken the drug for a month and has not had any headaches.
SiR,—Arellano
et
samples.
Of 615 patients tested 10I (16-4%) yielded C trachomatis. Clinical was noted in 179 patients, and 82 (45-8%) had detectable antigen by ELISA. The asymptomatic carriage rate in this urethritis
population was 4-4%, but of the 101 positive patients 19 (18-8%) were symptom-free. All of these symptom-free cases would have been unrecognised and untreated under our routine current policy. Examination of early morning urine seems to be a sensitive, non-invasive sampling method for detecting C trachomatis in males. This method is less reliable in females. These preliminary studies suggest that examination of early morning urine is more reliable than testing urethral swabs, when C trachomatis is being sought in a genitourinary clinic. 10-20% of swabs may turn out to be inadequate. Furthermore, in male patients with a low-grade infection C trachonzatis may not be detected in a urethral swab if the
patient has recently urinated.
The combination of inadequately taken urethral swabs and urination before clinic attendance would have significantly underestimated the incidence of C trachomatis infection in our patients if urethral swabs alone had been collected.
SIR,-Camylofin is a smooth-muscle relaxant used as an antispasmodic. In Brazil the proprietary name is ’EspasmoSilidron’ ; it contains 20 mg camylofm plus 40 mg dimethicone per 0-6 ml. In Europe and South Africa the proprietary name is ’Avacan’. A 30-day-old baby weighing 5-4 kg had increased bowel movements and abdominal cramps. His mother twice gave him 7 drops of espasmo-silidron (about 10 mg camylofm or 1-75 mg/kg). After the second dose the baby became pale, hypoactive, and cyanosed. Upon admission 6 h later, he was in deep coma with bilateral pinpoint pupils and respiratory depression requiring mechanical ventilation. Intravenous naloxone 0-02 mg/kg immediately reversed the clinical picture. 0-02 mg/kg doses had to be administered four more times in the next 16 h. The baby was discharged 3 days later. A 2-day-old baby weighing 4-0 kg was given 20 drops of espasmo-silidron twice, 30 min apart (a total of about 26 mg camylofm or 6-5 mg/kg) because of suspected colic. About 90 min later she was found with a very slow respiratory rate, cyanosis, and hypotonia, and was admitted unconscious to hospital, with bilateral pinpoint pupils, bradycardia, and intermittent apnoea requiring mechanical ventilation. Intravenous naloxone 0-02 mg/kg reversed the picture within minutes. An additional 0-02 mg/kg dose was needed 8 h after the first. The baby was discharged after 4 days. Camylofin is an antispasmodic of atropine-like and papaverinelike action. Side-effects in clinical use are thought to be negligible. However, it seems that ingestion of excessive amounts by infants produces symptoms of opioid intoxication. The good results obtained with naloxone, a pure opioid antagonist, support this. Even though the first naloxone dose led rapidly to improvement, several additional doses were necessary in one baby, as happens in other types of opioid intoxication.
As in the case presented by Arellano et al, the headaches started week after re-exposure to gemfibrozil and each intake precipitated a new episode 45-60 min later. The short half-life of gemfibrozil (1-5h) indicates that the headache was not related to reaching a steady-state (four to five times the half-life during continuous adminstration). The lowering of very-low-density lipoproteins by gemfibrozil takes 2-5 days, and reaches a peak 4 weeks later.2 We do not know how the lowering of plasma lipids might cause headache. one
JOSÉ ALVAREZ-SABIN Department of Neurology and Clinical Pharmacology, Hospital de la C S Vall d’Hebron, 08035 Barcelona, Spain
AGUSTIN CODINA CARLOS RODRÍGUEZ JOAN-RAMON LAPORTE
1. Arellano F, Dé Cos M, Valiente R, Quirós C Gemfibrozil-induced headache Lancet 1988; i: 705. 2 Illinworth DR. Lipid-lowering drugs an overview of indications and optimum
therapeutic use Drugs 1987, 33: 259-79.
NON-INVASIVE SAMPLING METHOD FOR DETECTING CHLAMYDIA TRACHOMATIS
SIR,—The establishment of Chlamydia trachomatzs as a major pathogen of the genital tract has led to an increased awareness of its role in pelvic inflammatory disease1.2 and infertility34 in the untreated female. The economic cost of investigating and treating the resultant infertility must be considerable; and the psychological cost alone in these women is often devastating. Awareness of the pathogenicity of C trachomatis has led to an increasing demand for screening, primarily, although not exclusively, in females attending genitourinary medicine clinics.5 Screening policies vary considerably in the UK. In our clinic all females are screened for C trachomatis, and positive women and their consorts are treated. All male clinic attenders with symptoms treated empirically. This policy has not controlled heterosexual transmission or the systemic infections arising from cervical infection since male patients have not always held their urine for the recommended three hours before urethral sampling for C trachomatis. There are also difficulties in recalling patients for an early morning slide to exclude urethritis. Nor does this policy make allowance for the recognition of the asymptomatic carriage of C trachomatis in the male urethra. We have done a study of all male patients attending our clinic for the first time, to evaluate the asymptomatic carriage of C trachomatis. This group would not normally be screened or treated for C trachomatis infection unless there were epidemiological grounds for doing so. We also wanted to evaluate the efficacy of early morning urine samples as a screening test. Patients were asked to collect an early morning sample, and on attendance at the clinic a urethral swab was taken, with a full clinical history. Swabs and urine were assayed for C trachomatis by an amplified ELISA (Boots-Celltech), and results on all urine samples are being confirmed by direct immunofluorescence (Syva ’Microtrak’), which we find better than cell culture for urine are
Department of Paediatrics, Instituto da Criança, Medical School, University of São Paulo, 05403 São Paulo
SP, Brazil
SAMUEL SCHVARTSMAN CLÁUDIO SCHVARTSMAN CLÁUDIO BARSANTI
AVAILABILITY OF ETHER
SIR,-Dr Bohmer and Dr Grounds (Oct 29, p 1022) ask whether anaesthetic ether may one day be unavailable. May & Baker are manufacturers of anaesthetic ether which, as Bohmer and Grounds point out, no longer has a product licence in the UK. It is, however, made available in the UK under sections 9 and 23 of the Medicines Act for individual patient treatment when there are very special circumstances. It is also available for export. There is no intention that anaesthetic ether should become unavailable and we are committed to continued manufacture. May & Baker Pharmaceuticals, Rhône-Poulenc Limited,
Dagenham, Essex RM10 7XS
J. O’GRADY
GEMFIBROZIL-INDUCED HEADACHE all described a patient with gemfibrozilinduced headache. We report another case. A 49-year-old man with hyperlipidaemia (type IV) had been treated with gemfibrozil 600 mg twice a day. After 4 weeks he had a holocephalic pulsatile headache of moderate intensity and frontotemporal predominance, a dry mouth, and slightly blurred vision. No neurological focal deficits, meningeal signs or papilloedema or other signs of intracranial hypertension were found. Computerised cranial tomography and lumbar puncture revealed no abnormality. His symptoms always appeared 45-60 min after taking gemfibrozil, receded after treatment with dipyrone or paracetamol, and reappeared after the night-time dose of gemfibrozil. After the drug was withdrawn, the patient had no more headaches. 4 weeks later gemfibrozil was re-started with the same regimen. After 7 symptom-free days, the same clinical picture occurred. At present (Oct 18, 1988) the patient has not taken the drug for a month and has not had any headaches.
SiR,—Arellano
et
samples.
Of 615 patients tested 10I (16-4%) yielded C trachomatis. Clinical was noted in 179 patients, and 82 (45-8%) had detectable antigen by ELISA. The asymptomatic carriage rate in this urethritis
population was 4-4%, but of the 101 positive patients 19 (18-8%) were symptom-free. All of these symptom-free cases would have been unrecognised and untreated under our routine current policy. Examination of early morning urine seems to be a sensitive, non-invasive sampling method for detecting C trachomatis in males. This method is less reliable in females. These preliminary studies suggest that examination of early morning urine is more reliable than testing urethral swabs, when C trachomatis is being sought in a genitourinary clinic. 10-20% of swabs may turn out to be inadequate. Furthermore, in male patients with a low-grade infection C trachonzatis may not be detected in a urethral swab if the
patient has recently urinated.
The combination of inadequately taken urethral swabs and urination before clinic attendance would have significantly underestimated the incidence of C trachomatis infection in our patients if urethral swabs alone had been collected.