MICONAZOLE TREATMENT AFTER RENAL TRANSPLANTATION

48

COFFEE AND TEA IN PSYCHIATRIC HOSPITALS

SIR,-The report by Dr Bowen and colleagues (May 30, p. 1217) eliminating coffee for one week in mentally retarded psychotic patients did not appear to affect plasma levels of neuroleptics in a consistent manner suffers from a number of problems. The patients’ previous levels of consumption were not specified. Could the inconsistency in effects on neuroleptic levels have been due to differences in prior levels of caffeine intake? Different physiological effects as a function of level of intake have been reported.’ Second, the fact that Bowen et al. found no significant differences in psychotic symptoms when subjects were on or off coffee suggests either that they were not sufficiently regular users to show the well-

TYPES OF EXPOSURE IN ACUTE HEPATITIS TYPES B AND NON-A,NON-B

that

known withdrawal effects‘-4 or that the scale was insensitive to these, or both. If the patients were not normally heavy users of caffeine, it may not necessarily be justified to extrapolate from these results to a population of heavy users.5 Even if coffee and tea do not reduce levels of antipsychotic drugs, there are ample grounds for questioning their unrestricted use by psychiatric inpatients (and outpatients). Because tea and coffee are so widely used it is all too easy to forget that they contain centrally acting drugs and can cause and exacerbate pre-existing psychopathological states.6-11 The commonplace minimisation of the potential psychotoxicity of coffeel2 is reflected in the fact that decaffeinated coffee is not generally available on psychiatric wards. Sadly, patients who see fit to provide their own may find themselves regarded as deviant for this reason. Of what use is all this science if it is not applied? Department of Psychology, Institute of Psychiatry, London SE5 8AF

VICKY RIPPERE

NON-A,NON-B HEPATITIS IN MILAN SIR,-Dr Farrow and colleagues (May 2, p. 982) describe the epidemiological and clinical feature of non-A, non-B hepatitis in West’London. As they say, their epidemiological findings are very different from those reported by others. We describe the epidemiological pattern in cases of acute non-A,non-B hepatitis admitted to the infectious diseases clinic, L.Sacco Hospital, Milan, between Oct. 31, 1978, and March 31, 1981. The diagnosis of acute viral hepatitis was based on history, clinical symptoms, and aminotransferase levels at least ten times the upper limit of normal. NonA,non-B hepatitis was diagnosed by exclusion. Hepatitis A and hepatitis B were excluded by radioimmunoassay (Abbott Laboratories and cytomegalovirus and Epstein-Barr virus infections’were ruled out by complement fixation and immunofluorescence tests, respectively. Of the 541 cases of acute viral hepatitis admitted to the clinic in this period 121 (223%) had nonA,non-B, 318 (58 . 8%) had type B, and 102 ( 18 . 9% had type A

hepatitis. As in other series the non-A,non-B type of hepatitis was milder and of shorter duration than hepatitis B, as judged by the duration of jaundice and the peak serum bilirubin, alanine transferase, and gammaglobulin levels, and these differences were significant. T, Gosselin RE, Smith RP The tolerance of coffee drinkers to caffeine Clin Pharmacol Therap 1968; 9: 31-39 Dreisbach RH, Pfeiffer C Caffeine-withdrawal headache J Lab Clin Med 1943; 28: 1212-19 Goldstein A, Kaizer S Psychotropic effects of caffeine in man III. a questionnaire survey of coffee drinking and its effects in a group of housewives Clin Pharmacol Therap 1969; 10: 477-88. White BC, Lincoln CA, Pearce NW, et al. Anxiety and muscle tension as consequences of caffeine withdrawal Science 1980; 209: 1547-48. Winstead DK Coffee consumption among psychiatric inpatients. Am JPsythiat 1976; 133: 1447-50. McManany MC, Schube PG. Caffeine intoxication Report of a case the symptoms of which amounted to a psychosis. N Engl J Med 1936; 215: 616-20 Harrie JR. Caffeine and headache. JAMA 1970; 213: 628 Greden JF Anxiety or caffeinism a diagnostic dilemma Am J Psychiat 1974, 131: 1089-92. Lutz EG Restless legs, anxiety and caffeinism J Clin Psychiat 1978; 39: 693-98. Mikkelsen EJ. Caffeine and schizophrenia J Clin Psychiat 1978; 39: 732-36 De Freitas B, Schwartz G Effects of caffeine in chronic psychiatric patients Am J Psychiat 1979, 136: 1337-38 Editorial Coffee: Should we stop drinking it? Lancet 1981; i 256

1. Colton 2 3

4. 5. 6. 7

8 9

10 11. 12.

*Dental treatment, therapeutic skin punctures, minor surgery. t3 venereal (2 homosexual), 2 had been in close contact with another jaundiced person, and I lived in an institution.

ofnon-A,non-B

Among the 121 cases hepatitis, 28 were associated with transfusions and 48 with drug abuse. Only 45 cases (37 -2%) had an epidemiological pattern similar to that reported by Farrow et al. (see table). The mean age of these 45 patients was 39±15 years (range 15-73). There was no significant difference in the age distribution. 28 were males and 17 females. A common route of transmission for both hepatitis B and non-A, non-B hepatitis in Italy is shellfish ingestion. 16/541 cases (2-9% of the total) can be considered sporadic non-A, non-B hepatitis, a figure similar to that in Farrow’s series. The detection of sporadic cases of non-A,non-B hepatitis represents an indirect confirmation (as does post-transfusion hepatitis) of the existence of asymptomatic non-A,non-B virus(es) carriers. The prevalence of sporadic non-A,non-B hepatitis may be an indirect marker of the spread of infection. On this hypothesis, the low proportion of post-transfusion non-A,non-B hepatitis cases in Farrow’s report does not seem to accord with his data on sporadic cases.

Infectious Diseases Clinic,

University of Milan, L Sacco Hospital, 20157 Milan, Italy

F. CAREDDA A. D’ARMINIO MONFORTE E. ROSSI S. LOPEZ M. MORONI

MICONAZOLE TREATMENT AFTER RENAL TRANSPLANTATION

SIR,—Miconazole is a fungicidal agentl2 that, in contrast to amphotericin B, does not seem to be nephrotoxic.2,3 We have used miconazole to treata patient with chronic renal transplant rejection who had cryptococcal meningitis. A 30-year-old man underwent renal transplantation in 1976. At the time of his admission in 1980, the serum creatinine was 480 of a He presented with classical signs and subacute meningitis. The cerebrospinal fluid contained 75 cells/pl (60% lymphocytes), glucose 2 mmol/1 (normal 3-4-5-6), and protein 0 - 9 g/1 (normal <0 - 5). The titre of cryptococcal antigens in the CSF was 1/8. Fluid withdrawn by the cisternal route (lumbar punctures gave negative findings) showed cryptococci in an indianink preparation, and Cryptococcus neoformans, sensitive to amphotericin B, miconazole, and 5-fluorocytosine was cultured. Chest X-ray and computerised tomography of the lungs and brain demonstrated no mass lesions. Miconazole was given intravenously in a total daily dose of 2400 mg together with oral 5-fluorocytosine (75 pg/kg). Azathioprine was withdrawn and prednisolone was maintained at a dose of 10 mg daily. In the ensuing week the serum creatinine rose to 750 µmol/1. A renal biopsy revealed no evidence of acute rejection, but there was tubular vacuolation typical of drug induced damage. Miconazole was withdrawn briefly and then reintroduced at a lower dose of 1200

µmol/1.

symptoms

1. Van Cutsem J, Thienpont D. Miconazole, a broad-spectrum antimycotic agent with antibacterial activity. Chemotherapy 1972, 17: 392-404. 2 Scheef W, Symoens J, Van Camp K, et al. Chemotherapy of candidiasis. Br Med J 1974; i: 78. 3. Stevens DA, Levine HV, Deresinski SC. Miconazole in coccidioidomycosis II: Therapeutic and pharmacologic studies in man Am J Med 1976; 60: 191-202

49

Relation between intravenous function. Bx

=

renal

miconazole

therapy

and

renal

biopsy.

mg daily. Supplementary intrathecal therapy was given in a dose of 20 mg on six occasions. These changes and the subsequent relationship between the serum creatinine and miconazole therapy are shown in the figure. Repeated CSF examinations showed normal biochemistry, slight pleocytosis, but no evidence of active cryptococcal infection. The timing of the serum creatinine changes in relation to the dose of miconazole suggests that this patient’s acute renal failure was a consequence of therapy with this drug. The association of renal toxicity with miconazole therapy has not previously been reported, although one patient treated with a daily dose of 2100 mg was reported to show a falling creatinine clearance from 90 to 30 ml/min.4In patients with renal failure the volume of distribution of the drug is significantly lower, so plasma levels are higherthan those found in patients with normal renal function, even though the elimination half-life does not alter with chronic renal insufficiency. Rouleaux formation and red cell agglutination occurred in our patient. These changes have been reported by others in connection with miconazole and could have contributed to the development of renal failure, but the relationship observed between the improved renal function and the reduction in drug dose in this case, suggests a direct nephrotoxic mechanism. It would therefore seem wise to modify the dosage of miconazole when it is used in patients with chronic renal insufficiency.

therapy, 3,6

Renal Unit and Department of Pathology, Queen Elizabeth Hospital, Woodville, South Australia 5011

K. N. LAI M. NEWTON A. SEYMOUR D. PUGSLEY T. JONES

NEONATAL DISTALGESIC POISONING

SIR,-A 14-day-old male infant weighing 4 43 kg was brought to

hospital as an emergency. 2 h previously his 2-year-old brother had been discovered feeding him an unknown number of ’Distalgesic’ tablets. His mother, a nurse, at first thought ingestion unlikely because of the large tablet size, but one hour later the infant became pale, drowsy, and unresponsive with shallow respirations. On arrival at hospital he was pale, mottled, and limp. His pupils were markedly constricted and he was practically apnoeic with only 4. Neill HB. Miconazole carrier

solution, hyperlipidemia and hematologic problems. N Engl J Med 1977; 296: 1479. 5. Lewi PJ, Boelaert J, Daneels R, et al. Pharmacokinetic profile of intravenous miconazole in man: Comparison of normal subjects and patients with renal insufficiency. Europ J Clin Pharmacol 1976; 10: 49-54. 6. Sung JP, Grendahl JG. Side-effects of miconazole for systemic mycoses. N Engl J Med 1977; 297: 786-87.

occasional shallow gasps. Naloxone 0 .1 mg intramuscularly resulted in complete recovery after only 20-30 s. Magnesium sulphate 500 mg in solution was administered by nasogastric tube as a cathartic. At 4 h post-ingestion the plasma paracetamol was 1 1 mmol/l. Four further episodes of apnoea occurred at 6, 7, 10, and 11 h post-ingestion. Naloxone 0 1 mg was administered intravenously on three occasions and once by intramuscular injection, with immediate response every time. The therapeutic effect was more sustained after the intramuscular dose. Plasma alanine transaminase and glucose remained normal but there was a transient rise in aspartate transaminase to 49 U/1, perhaps reflecting iatrogenic muscle trauma. He was discharged home after four days and followup has shown no sequelae. We believe this to be the youngest recorded case of distalgesic poisoning. Distalgesic (paracetamol [acetaminophen] 325 mg, dextropropoxyphene 32 5 mg) is commonly encountered in nonaccidental overdosage in adults.’ The effects reflect the separate toxicities of its two constituents. Dextropropoxyphene causes recurrent respiratory depression which can be counteracted by repeated administration of naloxone, a pure narcotic antagonist. A recent report has highlighted the safety of naloxone in neonatal narcotic poisoning in doses exceeding those recommended by the manufacturer,2and Curnock has suggested its diagnostic use in any child with unexplained respiratory depression.3The paracetamol component proved innocuous in our case; plasma levels normally "toxic" in adults are well tolerated by young children.4 An infant with codeine-induced narcosis described by Dr Wilkes and colleagues (May 23, p. 1166) required mouth-to-mouth ventilation by his general practitioner until he reached hospital. Such action is laudable but should be unnecessary. The frequency of narcotic-induced respiratory depression, both in adults and children, is such that general practitioners should perhaps carry naloxone for such emergencies. Department of Child Health, University of Glasgow, Royal Hospital for Sick Children, Glasgow G3 8SJ; and Department of Paediatrics, Stobhill General Hospital, Glasgow

J. O. BEATTIE C. P. CHEN T. H. MACDONALD

NICOTINIC ACID AND SKIN TEMPERATURE

SIR,—Dr Phillips and Dr Lightman (April 4, p. 754) found that an injection of nicotinic acid caused an increase in facial temperature of almost 3°C. We measured temperature changes after giving 200 mg nicotinic acid orally to three subjects and observed the characteristic body and facial flush.5,6 Skin temperature, measured with thermistors and infrared thermometry (AGA 680, Medical Thermovision), was no different after ingestion of nicotinic acid. Our subjects were in a constant ambient temperature of25°C. Phillips and Lightman do not mention environmental conditions in their paper. This is important since the initial facial temperatures of about 33°C in fig. 1 of their paper are low (normally 34-35°C). We wonder if their experiments were done at a lower ambient temperature than ours and whether the results they obtained are dependent upon ambient temperature. If so, their evaluation ofantiprostaglandin activity in various compounds should be done under stricter ambient temperature control. Defence and Civil Institute of Environmental Medicine, P.O. Box 2000, Downsview, Ontario M3M 3B9, Canada

1.

S. D. LIVINGSTONE L. A. KUEHN

for concern. Br Med J 1980; 280: 1045-47. 2. Gober AE, Kearns GL, Yokel RA, Danziger L. Repeated naloxone administration for morphine overdose in a 1 month old infant. Pediatrics 1979; 63: 606-08. 3. Curnock DA. Respiratory depression due to unsuspected narcotic ingestion treated with naloxone Arch Dis Childh 1978; 53: 508-9 4. Rumack BH, Peterson RG Acetaminophen overdose: Incidence, diagnosis and management in 416 patients. Pediatrics 1978; 62 (suppl): 898-903. 5. Kuehn L, Livingstone S, Limmer R, Weatherson B. The effect of ethanol consumption on human heat exchange. In: Folinsee, Wagner, Borgia, Drinkwater, Gliner, Bedi, eds. Environmental Stress. New York: Academic Press, 1978: 303-13. 6. Livingstone S, Kuehn L, Limmer R, Weatherson B. The effect of alcohol on body heat loss. Aviat Space Environ Med 1980, 51: 961-64

Young RJ, Lawson AAH. Distalgesic poisoning: Cause