- Email: [email protected]
LEUKAEMIA IN AN AIDS PATIENT
1361 MEASUREMENT OF FETAL pH IN THE GUINEAPIG BY NMR
SiR,-Antenatal monitoring has considerably increased the safety of the fetus and the newborn. Cerebral palsy caused by hypoxia can be avoided to a considerable extent. Nevertheless today’s methods have shortcomings. Fetal heart rate monitoring is sensitive but not very specific and false positive results lead to many unnecessary terminations of labour. Fetal blood analysis is a reliable way of recognising imminent fetal hypoxia but the method requires that the membran’es be ruptured so it can only be done during labour. 31 P in-vivo nuclear magnetic resonance (NMR) spectroscopy permits the non-invasive determination of pH in fetal tissue from the chemical shift of inorganic phosphorus (P) with respect to phospho creatinine. We used a Bruker tomograph (BNT IS 24/30) at a field strength of 2-44 T. A series of cross-sections of the pregnant guineapigs with a gestational age of 56-59 days were obtained using the twodimensional Fourier transform technique to localise the fetuses. For technical reasons there is an interval between the tomography and the spectroscopy, during which the fetus can alter its position. So, after laparotomy and uterotomy under ketamine/xylazine anaesthesia, the head of the fetus was fixed to the abdominal wall to allow the maintenance of the position of the fetal brain ona surface coil (4 cm diameter). Such fixation of the fetal head will be superfluous in the near future when NMR equipment becomes available that will provide imaging and spectroscopy at the same time. Such NMR systems should permit the method to be applied to the human fetus. The guineapig fetuses were catheterised to permit withdrawal of arterial blood samples. 31 P scans were at 40 - 5 MHz, 100 scans being done with a scanning time of 2 s. We measured the pH level in this way directly in the brains of five guineapig fetuses.
pH VALUES
IN FETAL BLOOD SAMPLES AND BY MEANS OF
FETAL
i
P NMR IN
BRAIN* .,
-
"
m
-.-
i
SP= sugar phosphate, Pi = inorganic phosphate; PCr = phosphocreatinine. *More than
one measurement m
each animal.
SP
Fetal blood samples withdrawn from the catheters were analysed on pH meter (Radiometer PHM 72-BMS 2). pH calculated from the chemical shift of inorganic phosphate and pH in fetal blood are compared in the table. These data suggest that it is possible in high-risk pregnancies to measure the pH directly in the brain of the unborn infant without rupturing the membranes. a
D-1000 Berlin 44, West Germany
K. LANGNER S. SCHMIDT J. W. DUDENHAUSEN E. SALING
Bruker Co, Karlsruhe
H. FRIEDBURG D. HÖPFEL
Institute of Perinatal Medicine, Free University of Berlin,
Radiometer Co,
Copenhagen, Denmark
HTLV-POSITIVE T-CELL LYMPHOMA/LEUKAEMIA IN AN AIDS PATIENT
SIR,-Two T-lymphotropic retroviruses have been associated with acquired immunodeficiency syndrome (AIDS); one is human T-cell leukaemia virus (HTLV) type I and the other is lymphadenopathy-associated virus or HTLV type III. HTLV-I is the causative agent of adult T-cell lymphoma/leukaemia (ATL). We report here a case of ATL diagnosed 17 months after an episode of Pneumocystis carinii pneumonia in a previously healthy HTLV-I carrier. The patient was a 36-year-old Japanese woman who presented with P carinii pneumonia and scabies in April, 1982.1 She had no history of promiscuity, drug abuse, or blood transfusion. Her husband is healthy and heterosexual. She was successfully cured of both diseases but had severe herpes zoster in November, 1982. She subsequently did well until May, 1983, when she began to have intermittent fever. T-cell subset analysis in June, 1983, revealed ratio (0 - 64) with a decrease of reversal of the helper T-cells (0-47X 10 /1). Purified protein derivative skin tests were negative and the lymphocyte response to mitogens was reduced. Furthermore, she was found to be seropositive for HTLV-I antigens and HTLV-I particles were demonstrated in short-term cultures of peripheral blood lymphocytes.2Her mother was also seropositive but her husband and sister were seronegative. In July, 1983, swelling of the cervical lymph nodes was noted; biopsy was not diagnostic. In the beginning of September, 1983, the cervical lymphadenopathy became more pronounced and there was hepatosplenomegaly. A repeat biopsy of the cervical lymph nodes showed diffuse lymphoma of the pleomorphic type. She was given several courses of combination chemotherapy with cyclophosphamide, vincristine, and prednisolone but the response was transient and incomplete. On Jan 12, 1984, her white blood-cell count rose to 15x 109/1, with 40% abnormal lymphocytes with indented or lobulated nuclei. These lobulated lymphocytes were E+, Leu-1+, Leu-2a-, and Leu-3a+. Multiple skin nodules soon appeared on the trunk and biopsy revealed leukaemic infiltration in the dermis and subcutaneous tissue. Terminally, meningeal leukaemia developed and the patient died on March 20, 1984. The proviral DNA of HTLV-I was detected by Southern blot hybridisation in her peripheral blood leukaemic cells and in the lymphomatous tissues obtained by biopsy and at necropsy. The clinical and laboratory features of our patient are consistent with those of AIDS. However, this case is unusual in that opportunistic infections such as P carinii pneumonia and herpes zoster were followed by the development of ATL. ATL was diagnosed 17 months after the episode of P carinii pneumonia and during this period there was no evidence of smouldering ATL.3 The patient was a carrier of HTLV-I and her tumour cells contained the HTLV-I I genome. Although Kaposi’s sarcoma and B-cell lymphoma have
helper/suppressor
1. ...
2.
31
P NMR spectrum of brain of guineapig fetus. Spectrum
represents total of 100 scans, each of 2
s scanning-time.
N. HELLEDIE
Kobayashi M, Miyoshi I, Sonobe H, Taguchi H, Kubonishi I. Association of Pneumocystis carinii pneumonia and scabies JAMA 1982; 248: 1973. Miyoshi I, Kobayashi M, Yoshimoto S, et al. ATLV in Japanese patient with AIDS. Lancet
3.
1983; ii: 275.
Yamaguchi K, Nishimura H, Kohrogi H, et al. A proposal for smoldering adult T-cell leukemia: a clinicopathologic study of five cases. Blood 1983; 62: 758-66.
1362 been frequently observed in patients with AIDS, there has been no report of the association of ATL and AIDS. HTLV-I preferentially infects helper T-cells and its carriers are more prone to infection by various pathogenic organisms.4In our case HTLV-I probably rendered the host susceptible to the opportunistic infections by causing cellular immune dysfunction which may have accelerated the development of ATL as well. The natural history of HTLV-II carriers should be explored in relation to the nature of immunodeficiency and leukaemogenesis by HTLV-I.
Kochi Medical School, Kochi 781-51, Japan
MAKOTO KOBAYASHI SHIZUO YOSHIMOTO MASATOSHI FUJISHITA SHOKI YANO KENJI NIIYA ICHIRO KUBONISHI HIROKUNI TAGUCHI ISAO MIYOSHI
DRUG-RELATED PNEUMONITIS AND DRUG-INDUCED HYPERSENSITIVITY PNEUMONITIS
SIR,-Dr Venet and his colleagues (April 28, p 962) state that amiodarone pneumonitis is immunologically mediated, and they underline the diagnostic value of cell data from bronchoalveolar lavage (BAL). We agree and would like to add some comments related to other drug-induced hypersensitivity pneumonitis. For amiodarone pneumonitis a cell-mediated immunological mechanism seems likely for three reasons. First, in our review of 51 published cases5the pneumonitis seemed not to be dose dependent; daily doses ranged from 200 mg to 1000 mg and the treatments lasted for between one month and nine years. Second, of the 5 cases in which BAL was done 4 had lymphocytosis (23-59%) resembling the hypersensitivity pneumonitis due to inhalation of organic dusts and whose immunological mechanism is well established.Third, in a similar case (case 17) we observed lymphocytosis of BAL fluid together with an inverted OKT::OKT; ratio: simultaneously peripheral T lymphocytes displayed a secretion of leucocyte inhibitory factor in the presence of different concentrations of amiodarone, which favours a cell-mediated hypersensitivity. The diagnostic interest of cell data on BAL fluid should be extended to other drug-induced hypersensitivity pneumonitis. The table shows results from 5 patients with drug-induced pneumonitis, all with the clinical characteristics of hypersensitivity pneumonitis. In all cases the BAL fluid displayed a lymphocytosis and a low helper: suppressor cell ratio; in 2 patients this ratio was calculated in the peripheral blood also and was normal (cases 1 and 2). This lymphocytosis and inverted lymphocyte subset ratio have also been found in hypersensitivity pneumonitis due to organic dusts.6,8 In M, McLane M, Lee TH, Mullins J, Tachibana N. Role of HTLV in immunosuppression. In Gallo RC, Essex M, Gross L, eds. Human T-cell leukemia lymphoma virus. New York Cold Spring Harbor Laboratory (in press).
4. Essex
5. Akoun G, Milleron B, Mayaud C Le poumon de l’amiodarone. Rev Pneumol Clin 1984, 40: 41-45. 6. Leatherman JW, Michael AF, Kronenberg RS, Schwartz BS, Hoidal JR. Evaluation of cell-mediated immunity in the lung by monoclonal antibodies in hypersensitivity pneumonitis and asymptomatic pigeon breeders. Am Rev Resp Dis 1983; 127: 62. 7. Akoun GM, Gauthier-Rahman S, Milleron BJ, Perrot JY, Mayaud CM. Amiodaroneinduced hypersensitivity pneumonitis: Evidence ofan immunological cell-mediated mechanism. Chest 1984, 85: 133-35. 8. Hirata T, Nagai S, Ohshima S, Izumi T. Comparative study ofT-cell subsets in BAL fluid in patients with hypersensitivity pneumonitis and sarcoidosis Chest 1982, 82: 232
one patient9 (case 4), 54 days after acebutolol was withdrawn, its administration was resumed for 37 days; BAL fluid lymphocytosis decreased at the end of the drug withdrawal period and increased when the drug was taken again. This analysis of cells in BAL fluid points to an immunological mechanism for some cases of drug-induced pneumonitis; BAL may be of diagnostic value and obviate the need for biopsy.
Unit, Hôpital Tenon, 75020 Paris, France
G. M. AKOUN C. M. MAYAUD B. J. MILLERON
Laboratory of Applied Immunology, Hôpital de l’Hôtel-Dieu, Paris
J. Y. PERROT
Chest Disease
ADVERSE REACTIONS TO PIPERACILLIN IN PATIENTS WITH CYSTIC FIBROSIS
SIR,-Dr Stead and colleagues (April 4, p 857) report a high percentage of adverse reactions to piperacillin in the treatment of Pseudomonas aererginosa infections in patients with cystic fibrosis (CF). Our experience accords with theirs since we have seen adverse reactions in 13 of 18 patients treated with piperacillin in combination with an aminoglycoside during the past 17 months. The 18 patients were 7-34 years of age (mean 19); 7 were males. All patients were treated because of lower respiratory tract infection due to Ps aerllginosa. The mean daily dose of piperacillin was 410
mg/kg body weight (range 342-460). 13 patients (72%) had adverse reactions during treatment. 8 patients reacted during their first course with piperacillin after a mean of 14 days (range 9-22) and 5 patients during their second course after a mean of 5 days (range first infusion to 15 days). There were no differences in doses, combined aminoglycoside, or duration of treatment between the patients with adverse reactions and the others. All but 2 patients had a temperature above 38°C. 3 patients had a rash, 2 pruritus, 2 tender lymphadenitis, and 2 showed slight blood eosinophilia. The 1 patient reacting to the first dose in the second course had a more severe reaction with respiratory symptoms. All patients recovered within a few days of discontinuation of treatment and the fever disappeared in 24-36 h. 8 of the 13 patients had previously been treated with azlocillin, another synthetic ureidopenicillin given in a daily dose of 600 mg/kg body weight. These patients had received one to nine courses of azlocillin in combination with an aminoglycoside.1,2 2 of the 8 patients had adverse reactions to this antibiotic also-1 on his second course and 1 on his fifth course, 4 months after he had reacted to piperacillin. The 5 patients not showing adverse reactions to piperacillin had been treated with one to eight courses of azlocillin in corresponding dosages, durations, and combinations. 2 of the 6 patients reacting to piperacillin but tolerating azlocillin (six and nine courses) had previously reacted seriously with trigonum cystitis to carbenicillin. By the end of May 1984, we had given seventy-six courses of azlocillin to 28 patients with CF; 4 (14%) reacted adversely during their second to fifth course of azlocillin. We can thus confirm the observation of Stead and colleagues that piperacillin seems to give a higher percentage of adverse reactions than azlocillin and that it does not seem to be suitable to patients with CF-at least not as first choice. In the light of our experience we do not understand why Dr Brock and Maryanne Roach (May 12, p 1070) state that the suggestion that high-dose semisynthetic penicillin therapy in patients with CF may provoke a febrile response "needs to be resolved".
LYMPHOCYTE STUDIES OF BAL FLUID IN FIVE CASES OF DRUG-INDUCED HYPERSENSITIVITY PNEUMONITIS
Department of Paediatrics, Karolinska Institutet,
Huddinge University Hospital, S-141 86 Huddinge, Sweden
BIRGITTA STRANDVIK
9. Akoun
GM, Herman DP, Mayaud CM, Perrot JY. Acebutolol-induced hypersensitivity pneumonitis. Br Med J1983, 286: 266-67. 1. Malmborg AS, Alfredsson H, Kusoffsky E, Strandvik B. Aclocillin and gentamicin in respiratory tract infections with Pseudomonas aeruginosa in patients with cystic fibrosis. Scand J Inf Dis 1981, suppl 29 64-69. 2. Malmborg AS, Alfredsson H, Strandvik B Aziocillin in cystic fibrosis Isr Med Sci 1983, 19: 1001-3.
SiR,-Antenatal monitoring has considerably increased the safety of the fetus and the newborn. Cerebral palsy caused by hypoxia can be avoided to a considerable extent. Nevertheless today’s methods have shortcomings. Fetal heart rate monitoring is sensitive but not very specific and false positive results lead to many unnecessary terminations of labour. Fetal blood analysis is a reliable way of recognising imminent fetal hypoxia but the method requires that the membran’es be ruptured so it can only be done during labour. 31 P in-vivo nuclear magnetic resonance (NMR) spectroscopy permits the non-invasive determination of pH in fetal tissue from the chemical shift of inorganic phosphorus (P) with respect to phospho creatinine. We used a Bruker tomograph (BNT IS 24/30) at a field strength of 2-44 T. A series of cross-sections of the pregnant guineapigs with a gestational age of 56-59 days were obtained using the twodimensional Fourier transform technique to localise the fetuses. For technical reasons there is an interval between the tomography and the spectroscopy, during which the fetus can alter its position. So, after laparotomy and uterotomy under ketamine/xylazine anaesthesia, the head of the fetus was fixed to the abdominal wall to allow the maintenance of the position of the fetal brain ona surface coil (4 cm diameter). Such fixation of the fetal head will be superfluous in the near future when NMR equipment becomes available that will provide imaging and spectroscopy at the same time. Such NMR systems should permit the method to be applied to the human fetus. The guineapig fetuses were catheterised to permit withdrawal of arterial blood samples. 31 P scans were at 40 - 5 MHz, 100 scans being done with a scanning time of 2 s. We measured the pH level in this way directly in the brains of five guineapig fetuses.
pH VALUES
IN FETAL BLOOD SAMPLES AND BY MEANS OF
FETAL
i
P NMR IN
BRAIN* .,
-
"
m
-.-
i
SP= sugar phosphate, Pi = inorganic phosphate; PCr = phosphocreatinine. *More than
one measurement m
each animal.
SP
Fetal blood samples withdrawn from the catheters were analysed on pH meter (Radiometer PHM 72-BMS 2). pH calculated from the chemical shift of inorganic phosphate and pH in fetal blood are compared in the table. These data suggest that it is possible in high-risk pregnancies to measure the pH directly in the brain of the unborn infant without rupturing the membranes. a
D-1000 Berlin 44, West Germany
K. LANGNER S. SCHMIDT J. W. DUDENHAUSEN E. SALING
Bruker Co, Karlsruhe
H. FRIEDBURG D. HÖPFEL
Institute of Perinatal Medicine, Free University of Berlin,
Radiometer Co,
Copenhagen, Denmark
HTLV-POSITIVE T-CELL LYMPHOMA/LEUKAEMIA IN AN AIDS PATIENT
SIR,-Two T-lymphotropic retroviruses have been associated with acquired immunodeficiency syndrome (AIDS); one is human T-cell leukaemia virus (HTLV) type I and the other is lymphadenopathy-associated virus or HTLV type III. HTLV-I is the causative agent of adult T-cell lymphoma/leukaemia (ATL). We report here a case of ATL diagnosed 17 months after an episode of Pneumocystis carinii pneumonia in a previously healthy HTLV-I carrier. The patient was a 36-year-old Japanese woman who presented with P carinii pneumonia and scabies in April, 1982.1 She had no history of promiscuity, drug abuse, or blood transfusion. Her husband is healthy and heterosexual. She was successfully cured of both diseases but had severe herpes zoster in November, 1982. She subsequently did well until May, 1983, when she began to have intermittent fever. T-cell subset analysis in June, 1983, revealed ratio (0 - 64) with a decrease of reversal of the helper T-cells (0-47X 10 /1). Purified protein derivative skin tests were negative and the lymphocyte response to mitogens was reduced. Furthermore, she was found to be seropositive for HTLV-I antigens and HTLV-I particles were demonstrated in short-term cultures of peripheral blood lymphocytes.2Her mother was also seropositive but her husband and sister were seronegative. In July, 1983, swelling of the cervical lymph nodes was noted; biopsy was not diagnostic. In the beginning of September, 1983, the cervical lymphadenopathy became more pronounced and there was hepatosplenomegaly. A repeat biopsy of the cervical lymph nodes showed diffuse lymphoma of the pleomorphic type. She was given several courses of combination chemotherapy with cyclophosphamide, vincristine, and prednisolone but the response was transient and incomplete. On Jan 12, 1984, her white blood-cell count rose to 15x 109/1, with 40% abnormal lymphocytes with indented or lobulated nuclei. These lobulated lymphocytes were E+, Leu-1+, Leu-2a-, and Leu-3a+. Multiple skin nodules soon appeared on the trunk and biopsy revealed leukaemic infiltration in the dermis and subcutaneous tissue. Terminally, meningeal leukaemia developed and the patient died on March 20, 1984. The proviral DNA of HTLV-I was detected by Southern blot hybridisation in her peripheral blood leukaemic cells and in the lymphomatous tissues obtained by biopsy and at necropsy. The clinical and laboratory features of our patient are consistent with those of AIDS. However, this case is unusual in that opportunistic infections such as P carinii pneumonia and herpes zoster were followed by the development of ATL. ATL was diagnosed 17 months after the episode of P carinii pneumonia and during this period there was no evidence of smouldering ATL.3 The patient was a carrier of HTLV-I and her tumour cells contained the HTLV-I I genome. Although Kaposi’s sarcoma and B-cell lymphoma have
helper/suppressor
1. ...
2.
31
P NMR spectrum of brain of guineapig fetus. Spectrum
represents total of 100 scans, each of 2
s scanning-time.
N. HELLEDIE
Kobayashi M, Miyoshi I, Sonobe H, Taguchi H, Kubonishi I. Association of Pneumocystis carinii pneumonia and scabies JAMA 1982; 248: 1973. Miyoshi I, Kobayashi M, Yoshimoto S, et al. ATLV in Japanese patient with AIDS. Lancet
3.
1983; ii: 275.
Yamaguchi K, Nishimura H, Kohrogi H, et al. A proposal for smoldering adult T-cell leukemia: a clinicopathologic study of five cases. Blood 1983; 62: 758-66.
1362 been frequently observed in patients with AIDS, there has been no report of the association of ATL and AIDS. HTLV-I preferentially infects helper T-cells and its carriers are more prone to infection by various pathogenic organisms.4In our case HTLV-I probably rendered the host susceptible to the opportunistic infections by causing cellular immune dysfunction which may have accelerated the development of ATL as well. The natural history of HTLV-II carriers should be explored in relation to the nature of immunodeficiency and leukaemogenesis by HTLV-I.
Kochi Medical School, Kochi 781-51, Japan
MAKOTO KOBAYASHI SHIZUO YOSHIMOTO MASATOSHI FUJISHITA SHOKI YANO KENJI NIIYA ICHIRO KUBONISHI HIROKUNI TAGUCHI ISAO MIYOSHI
DRUG-RELATED PNEUMONITIS AND DRUG-INDUCED HYPERSENSITIVITY PNEUMONITIS
SIR,-Dr Venet and his colleagues (April 28, p 962) state that amiodarone pneumonitis is immunologically mediated, and they underline the diagnostic value of cell data from bronchoalveolar lavage (BAL). We agree and would like to add some comments related to other drug-induced hypersensitivity pneumonitis. For amiodarone pneumonitis a cell-mediated immunological mechanism seems likely for three reasons. First, in our review of 51 published cases5the pneumonitis seemed not to be dose dependent; daily doses ranged from 200 mg to 1000 mg and the treatments lasted for between one month and nine years. Second, of the 5 cases in which BAL was done 4 had lymphocytosis (23-59%) resembling the hypersensitivity pneumonitis due to inhalation of organic dusts and whose immunological mechanism is well established.Third, in a similar case (case 17) we observed lymphocytosis of BAL fluid together with an inverted OKT::OKT; ratio: simultaneously peripheral T lymphocytes displayed a secretion of leucocyte inhibitory factor in the presence of different concentrations of amiodarone, which favours a cell-mediated hypersensitivity. The diagnostic interest of cell data on BAL fluid should be extended to other drug-induced hypersensitivity pneumonitis. The table shows results from 5 patients with drug-induced pneumonitis, all with the clinical characteristics of hypersensitivity pneumonitis. In all cases the BAL fluid displayed a lymphocytosis and a low helper: suppressor cell ratio; in 2 patients this ratio was calculated in the peripheral blood also and was normal (cases 1 and 2). This lymphocytosis and inverted lymphocyte subset ratio have also been found in hypersensitivity pneumonitis due to organic dusts.6,8 In M, McLane M, Lee TH, Mullins J, Tachibana N. Role of HTLV in immunosuppression. In Gallo RC, Essex M, Gross L, eds. Human T-cell leukemia lymphoma virus. New York Cold Spring Harbor Laboratory (in press).
4. Essex
5. Akoun G, Milleron B, Mayaud C Le poumon de l’amiodarone. Rev Pneumol Clin 1984, 40: 41-45. 6. Leatherman JW, Michael AF, Kronenberg RS, Schwartz BS, Hoidal JR. Evaluation of cell-mediated immunity in the lung by monoclonal antibodies in hypersensitivity pneumonitis and asymptomatic pigeon breeders. Am Rev Resp Dis 1983; 127: 62. 7. Akoun GM, Gauthier-Rahman S, Milleron BJ, Perrot JY, Mayaud CM. Amiodaroneinduced hypersensitivity pneumonitis: Evidence ofan immunological cell-mediated mechanism. Chest 1984, 85: 133-35. 8. Hirata T, Nagai S, Ohshima S, Izumi T. Comparative study ofT-cell subsets in BAL fluid in patients with hypersensitivity pneumonitis and sarcoidosis Chest 1982, 82: 232
one patient9 (case 4), 54 days after acebutolol was withdrawn, its administration was resumed for 37 days; BAL fluid lymphocytosis decreased at the end of the drug withdrawal period and increased when the drug was taken again. This analysis of cells in BAL fluid points to an immunological mechanism for some cases of drug-induced pneumonitis; BAL may be of diagnostic value and obviate the need for biopsy.
Unit, Hôpital Tenon, 75020 Paris, France
G. M. AKOUN C. M. MAYAUD B. J. MILLERON
Laboratory of Applied Immunology, Hôpital de l’Hôtel-Dieu, Paris
J. Y. PERROT
Chest Disease
ADVERSE REACTIONS TO PIPERACILLIN IN PATIENTS WITH CYSTIC FIBROSIS
SIR,-Dr Stead and colleagues (April 4, p 857) report a high percentage of adverse reactions to piperacillin in the treatment of Pseudomonas aererginosa infections in patients with cystic fibrosis (CF). Our experience accords with theirs since we have seen adverse reactions in 13 of 18 patients treated with piperacillin in combination with an aminoglycoside during the past 17 months. The 18 patients were 7-34 years of age (mean 19); 7 were males. All patients were treated because of lower respiratory tract infection due to Ps aerllginosa. The mean daily dose of piperacillin was 410
mg/kg body weight (range 342-460). 13 patients (72%) had adverse reactions during treatment. 8 patients reacted during their first course with piperacillin after a mean of 14 days (range 9-22) and 5 patients during their second course after a mean of 5 days (range first infusion to 15 days). There were no differences in doses, combined aminoglycoside, or duration of treatment between the patients with adverse reactions and the others. All but 2 patients had a temperature above 38°C. 3 patients had a rash, 2 pruritus, 2 tender lymphadenitis, and 2 showed slight blood eosinophilia. The 1 patient reacting to the first dose in the second course had a more severe reaction with respiratory symptoms. All patients recovered within a few days of discontinuation of treatment and the fever disappeared in 24-36 h. 8 of the 13 patients had previously been treated with azlocillin, another synthetic ureidopenicillin given in a daily dose of 600 mg/kg body weight. These patients had received one to nine courses of azlocillin in combination with an aminoglycoside.1,2 2 of the 8 patients had adverse reactions to this antibiotic also-1 on his second course and 1 on his fifth course, 4 months after he had reacted to piperacillin. The 5 patients not showing adverse reactions to piperacillin had been treated with one to eight courses of azlocillin in corresponding dosages, durations, and combinations. 2 of the 6 patients reacting to piperacillin but tolerating azlocillin (six and nine courses) had previously reacted seriously with trigonum cystitis to carbenicillin. By the end of May 1984, we had given seventy-six courses of azlocillin to 28 patients with CF; 4 (14%) reacted adversely during their second to fifth course of azlocillin. We can thus confirm the observation of Stead and colleagues that piperacillin seems to give a higher percentage of adverse reactions than azlocillin and that it does not seem to be suitable to patients with CF-at least not as first choice. In the light of our experience we do not understand why Dr Brock and Maryanne Roach (May 12, p 1070) state that the suggestion that high-dose semisynthetic penicillin therapy in patients with CF may provoke a febrile response "needs to be resolved".
LYMPHOCYTE STUDIES OF BAL FLUID IN FIVE CASES OF DRUG-INDUCED HYPERSENSITIVITY PNEUMONITIS
Department of Paediatrics, Karolinska Institutet,
Huddinge University Hospital, S-141 86 Huddinge, Sweden
BIRGITTA STRANDVIK
9. Akoun
GM, Herman DP, Mayaud CM, Perrot JY. Acebutolol-induced hypersensitivity pneumonitis. Br Med J1983, 286: 266-67. 1. Malmborg AS, Alfredsson H, Kusoffsky E, Strandvik B. Aclocillin and gentamicin in respiratory tract infections with Pseudomonas aeruginosa in patients with cystic fibrosis. Scand J Inf Dis 1981, suppl 29 64-69. 2. Malmborg AS, Alfredsson H, Strandvik B Aziocillin in cystic fibrosis Isr Med Sci 1983, 19: 1001-3.