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Urine pH and panic disorder
1351
Rectal aminophylline gel in treatment of apnoea in premature newborn babies SiR,—The efficacy of theophylline in neonatal apnoea was first demonstrated in 1973.’ Several other investigators have since confirmed this finding z3 Theophylline is now recognised as the treatment of choice for apnoea in most centres. It can be given as an
oral liquid; the aminophylline salt is available as suppositories, rectal solution, or intravenous (iv) injection. These formulations are not ideal-iv injection is invasive; oral absorption can be impaired because of achlorhydria, prolonged gastric emptying, or unpredictable peristalsis;’ and uniformity of dose might not be achieved with suppositories.5 In 1989, suppositories were unobtainable from our usual suppliers, and the Royal Free Hospital pharmacy department began to manufacture them. This formulation proved unsatisfactory since the aminophylline content was not consistent. Because oral and iv routes had disadvantages in newborn babies, it was decided to investigate the formulation of a rectal gel. The product was tested for stability and uniformity of dose, and between October and December, 1990, this gel was used in 8 premature newborn babies. A mean dose of 8-45 mg/kg daily (range 6-25-15 3) was given, which achieved a mean steady state plasma concentration of 11 ’0 ug/ml (5’8--lS-3) (n = 17). Clinical assessment at the time of sampling showed treatment was successful in 7 of these babies. The formulation has been well accepted by nursing and medical staff, and is a convenient way to deliver an individually tailored theophylline dose.
26-55 pmol/1 to 79.6 J..tll101/l. Renal biopsy revealed moderate acute tubulointerstitial rejection. Prednisone was increased to 2-0 mg/kg and OKT3 restarted at 2-5 mg daily. However, because of documented OKT3 antibody and a persistently raised CD3 value (74%) on Feb 25, the OKT3 dose was increased to 5-0 mg on Feb 26. The immunosuppressive therapy used was: OKT3 Date Feb 21 22 23 24 25 26 28
PRED (mg/kg) 0-5 2-0 2-0 2.0 1-75 1-75
OKT3 .
(mg) antibody index -
..
4-6*
..
....
2-5 2-5 5-0
..
..
..
6-5tj’
....
*1/100d!
5mg/kgandCSA=5 Omg/kg
We thank Dr H. S. MacKinnon and the medical and nursing staff of the special care baby unit at Whittington Hospital for their cooperation.
Within 1 min of intravenous injection of 5-0 mg OKT3, the patient had a flushed face, swollen lips and eyelids consistent with angio-oedema, wheezing and laboured breathing indicative of laryngeal oedema, and urticaria on the trunk and extremities. The patient was treated effectively with antihistamines. Wheezing and laboured breathing resolved within an hour. Urticaria resolved more slowly, within 24 h. OKT3 was subsequently discontinued. This clinical picture, in conjunction with an increased OKT3 antibody index, suggests an acute, dose-related, IgE-mediated hypersensitivity response to OKT3. This anaphylactic response should be added to the potentially serious adverse effects of orthoclone OKT3, including pulmonary oedema, angina, dysrhythmias, hypertension, hypotension, and cardiopulmonary arrest. 3,4
Pharmacy Department, Whittington Hospital,
University of Winnipeg, Winnipeg, Manitoba
JOEL WERIER
Department of Surgery, University of Minnesota Hospital and Clinic, Minneapolis, Minnesota 55455, USA
ALAN H. S. CHEUNG ARTHUR J. MATAS
SARAH COONEY SORAYA DHILLON
London N19 5NF, UK
Pharmacy Department, Royal Free Hospital,
GARY BENNETT CHRISTINE TREHANE
London NW3 1. Kuzemko JA, Paala J. Apnoeic attacks Arch Dis Child 1973; 48: 406-08.
m
the newborn treated with
aminophylline.
2. Uauy R, Shapiro DL, Smith B, Warshaw JP. Treatment of severe apnoea in prematures with orally administered theophylline. Pediatrics 1975; 55: 595-98. 3 Davi MJ, Sankaran K, Simons KJ, et al. Physiologic changes induced by theophylline in the treatment of apnoea m preterm infants. J Pediatr 1978; 92: 91-95. 4. Morselli PL, Franco-Morsell R, Bossi L. Clinical pharmacokinetics in newborns and infants: age related differences and therapeutic implications. Clin Pharmacokin 1980, 5: 485-527. 5 Waxler SH, Schack JA. Administration of aminophylline (theophylline ethylenediamine). JAMA 1950; 143: 736-40.
DJ, Shield CF, Barry JM, et al. Therapeutic use of OKT3 monoclonal antibody for acute renal allograft rejection. Nephron 1987; 46 (suppl 1): 41-47. 2. Herbert D, Sibley RK, Mauer SM. Recurrence of hemolytic uremic syndrome m renal transplant recipients. Kidney Int 1986; 30: 551-56. 3. Lee CW, Logan JL, Zukoski CF. Cardiovascular collapse following Orthoclone OKT3 administration: a case report. Am J Kidney Dis 1991; 17: 73-75. 4. Thistlewait JR, Stuart JK, Mayes JT, et al. Complications and monitoring of OKT3 therapy. Am JKidney Dis 1988; 16: 112-19. 1. Norman
Urine
Anaphylactic hypersensitivity reaction after repeat OKT3 treatment SIR,-’Orthoclone OKT3’ is a murine monoclonal antibody directed against the CD3 subset of T lymphocytes that has been widely used as an immunosuppressive agent in renal transplant recipients_1 As far as we are aware anaphylactic hypersensitivity reactions have not been reported in association with OKT3 treatment.
A twenty-two-month-old boy weighing 11 -5 kg, with end-stage renal failure due to haemolytic uraemic syndrome (HUS) at nine months of age, was admitted to the University of Minnesota transplant service. He had an uneventful living-related kidney transplant on Jan 16, 1991. Because antilymphocyte globulin has been implicated in the recurrence of HUS,z OKT3 was given postoperatively as prophylactic induction therapy for fourteen days without any adverse effects. The patient was discharged on a maintenance triple immunosuppressive regimen of prednisone (PRED), azathioprine (AZA), and cyclosporin (CSA). On Feb 16, 1991, the patient was admitted to a local community hospital with pseudomonas Hickman-line sepsis and citrobacter urinary tract infection. He was maintained on his usual immunosuppressive regimen but was treated with appropriate antibiotics and removal of the infected Hickman catheter, with subsequent resolution of all infections. However, on Feb 21, he was readmitted to the University of Minnesota after creatinine rose from
pH and panic disorder
SiR,-Papp and Gorinatil reported that urine pH may be useful in screening for panic disorder. They found that patients with this disorder had a significantly higher pH value than did controls. In an effort to replicate this finding, we measured urine pH with indicator paper (Fischer ’Alkacid Full Range’ pH kit) in 17 patients with symptomatic panic disorder and 17 healthy controls. Neither group of patients was taking any drugs. pH values were read within 1 min of urine collection by the same person, who was blind to the hypothesis. In view of the large difference between groups Papp and Gorman reported, the probability of a type II error (ie, falsenegative finding) with this sample size is less than 0.01.2 There were 10 women and 7 men in each group. Mean age did not differ between patients (31-5 [SD 7-9] years) and controls (27-8 [4-6]), and nor did mean urine pH (6-1 [0-7] and 6-0 [0-8], respectively). We therefore could not confirm that urine pH might be used as a screening device for the evaluation of respiratory status in panic disorder. Department of Psychiatry, Wayne State University and Lafayette Clinic, Detroit. Michigan 48207, USA 1.
RICHARD BALON ROBERT POHL VIKRAM K. YERAGANI
Papp LA, Gorman JM Urine pH in panic: a possible screening device. Lancet 1990; 335: 355.
D, Campbell MJ Statistical tables for the Blackwell Scientific Publications, 1987: 88.
2. Machin
design of clinical
trials. Oxford:
Rectal aminophylline gel in treatment of apnoea in premature newborn babies SiR,—The efficacy of theophylline in neonatal apnoea was first demonstrated in 1973.’ Several other investigators have since confirmed this finding z3 Theophylline is now recognised as the treatment of choice for apnoea in most centres. It can be given as an
oral liquid; the aminophylline salt is available as suppositories, rectal solution, or intravenous (iv) injection. These formulations are not ideal-iv injection is invasive; oral absorption can be impaired because of achlorhydria, prolonged gastric emptying, or unpredictable peristalsis;’ and uniformity of dose might not be achieved with suppositories.5 In 1989, suppositories were unobtainable from our usual suppliers, and the Royal Free Hospital pharmacy department began to manufacture them. This formulation proved unsatisfactory since the aminophylline content was not consistent. Because oral and iv routes had disadvantages in newborn babies, it was decided to investigate the formulation of a rectal gel. The product was tested for stability and uniformity of dose, and between October and December, 1990, this gel was used in 8 premature newborn babies. A mean dose of 8-45 mg/kg daily (range 6-25-15 3) was given, which achieved a mean steady state plasma concentration of 11 ’0 ug/ml (5’8--lS-3) (n = 17). Clinical assessment at the time of sampling showed treatment was successful in 7 of these babies. The formulation has been well accepted by nursing and medical staff, and is a convenient way to deliver an individually tailored theophylline dose.
26-55 pmol/1 to 79.6 J..tll101/l. Renal biopsy revealed moderate acute tubulointerstitial rejection. Prednisone was increased to 2-0 mg/kg and OKT3 restarted at 2-5 mg daily. However, because of documented OKT3 antibody and a persistently raised CD3 value (74%) on Feb 25, the OKT3 dose was increased to 5-0 mg on Feb 26. The immunosuppressive therapy used was: OKT3 Date Feb 21 22 23 24 25 26 28
PRED (mg/kg) 0-5 2-0 2-0 2.0 1-75 1-75
OKT3 .
(mg) antibody index -
..
4-6*
..
....
2-5 2-5 5-0
..
..
..
6-5tj’
....
*1/100d!
5mg/kgandCSA=5 Omg/kg
We thank Dr H. S. MacKinnon and the medical and nursing staff of the special care baby unit at Whittington Hospital for their cooperation.
Within 1 min of intravenous injection of 5-0 mg OKT3, the patient had a flushed face, swollen lips and eyelids consistent with angio-oedema, wheezing and laboured breathing indicative of laryngeal oedema, and urticaria on the trunk and extremities. The patient was treated effectively with antihistamines. Wheezing and laboured breathing resolved within an hour. Urticaria resolved more slowly, within 24 h. OKT3 was subsequently discontinued. This clinical picture, in conjunction with an increased OKT3 antibody index, suggests an acute, dose-related, IgE-mediated hypersensitivity response to OKT3. This anaphylactic response should be added to the potentially serious adverse effects of orthoclone OKT3, including pulmonary oedema, angina, dysrhythmias, hypertension, hypotension, and cardiopulmonary arrest. 3,4
Pharmacy Department, Whittington Hospital,
University of Winnipeg, Winnipeg, Manitoba
JOEL WERIER
Department of Surgery, University of Minnesota Hospital and Clinic, Minneapolis, Minnesota 55455, USA
ALAN H. S. CHEUNG ARTHUR J. MATAS
SARAH COONEY SORAYA DHILLON
London N19 5NF, UK
Pharmacy Department, Royal Free Hospital,
GARY BENNETT CHRISTINE TREHANE
London NW3 1. Kuzemko JA, Paala J. Apnoeic attacks Arch Dis Child 1973; 48: 406-08.
m
the newborn treated with
aminophylline.
2. Uauy R, Shapiro DL, Smith B, Warshaw JP. Treatment of severe apnoea in prematures with orally administered theophylline. Pediatrics 1975; 55: 595-98. 3 Davi MJ, Sankaran K, Simons KJ, et al. Physiologic changes induced by theophylline in the treatment of apnoea m preterm infants. J Pediatr 1978; 92: 91-95. 4. Morselli PL, Franco-Morsell R, Bossi L. Clinical pharmacokinetics in newborns and infants: age related differences and therapeutic implications. Clin Pharmacokin 1980, 5: 485-527. 5 Waxler SH, Schack JA. Administration of aminophylline (theophylline ethylenediamine). JAMA 1950; 143: 736-40.
DJ, Shield CF, Barry JM, et al. Therapeutic use of OKT3 monoclonal antibody for acute renal allograft rejection. Nephron 1987; 46 (suppl 1): 41-47. 2. Herbert D, Sibley RK, Mauer SM. Recurrence of hemolytic uremic syndrome m renal transplant recipients. Kidney Int 1986; 30: 551-56. 3. Lee CW, Logan JL, Zukoski CF. Cardiovascular collapse following Orthoclone OKT3 administration: a case report. Am J Kidney Dis 1991; 17: 73-75. 4. Thistlewait JR, Stuart JK, Mayes JT, et al. Complications and monitoring of OKT3 therapy. Am JKidney Dis 1988; 16: 112-19. 1. Norman
Urine
Anaphylactic hypersensitivity reaction after repeat OKT3 treatment SIR,-’Orthoclone OKT3’ is a murine monoclonal antibody directed against the CD3 subset of T lymphocytes that has been widely used as an immunosuppressive agent in renal transplant recipients_1 As far as we are aware anaphylactic hypersensitivity reactions have not been reported in association with OKT3 treatment.
A twenty-two-month-old boy weighing 11 -5 kg, with end-stage renal failure due to haemolytic uraemic syndrome (HUS) at nine months of age, was admitted to the University of Minnesota transplant service. He had an uneventful living-related kidney transplant on Jan 16, 1991. Because antilymphocyte globulin has been implicated in the recurrence of HUS,z OKT3 was given postoperatively as prophylactic induction therapy for fourteen days without any adverse effects. The patient was discharged on a maintenance triple immunosuppressive regimen of prednisone (PRED), azathioprine (AZA), and cyclosporin (CSA). On Feb 16, 1991, the patient was admitted to a local community hospital with pseudomonas Hickman-line sepsis and citrobacter urinary tract infection. He was maintained on his usual immunosuppressive regimen but was treated with appropriate antibiotics and removal of the infected Hickman catheter, with subsequent resolution of all infections. However, on Feb 21, he was readmitted to the University of Minnesota after creatinine rose from
pH and panic disorder
SiR,-Papp and Gorinatil reported that urine pH may be useful in screening for panic disorder. They found that patients with this disorder had a significantly higher pH value than did controls. In an effort to replicate this finding, we measured urine pH with indicator paper (Fischer ’Alkacid Full Range’ pH kit) in 17 patients with symptomatic panic disorder and 17 healthy controls. Neither group of patients was taking any drugs. pH values were read within 1 min of urine collection by the same person, who was blind to the hypothesis. In view of the large difference between groups Papp and Gorman reported, the probability of a type II error (ie, falsenegative finding) with this sample size is less than 0.01.2 There were 10 women and 7 men in each group. Mean age did not differ between patients (31-5 [SD 7-9] years) and controls (27-8 [4-6]), and nor did mean urine pH (6-1 [0-7] and 6-0 [0-8], respectively). We therefore could not confirm that urine pH might be used as a screening device for the evaluation of respiratory status in panic disorder. Department of Psychiatry, Wayne State University and Lafayette Clinic, Detroit. Michigan 48207, USA 1.
RICHARD BALON ROBERT POHL VIKRAM K. YERAGANI
Papp LA, Gorman JM Urine pH in panic: a possible screening device. Lancet 1990; 335: 355.
D, Campbell MJ Statistical tables for the Blackwell Scientific Publications, 1987: 88.
2. Machin
design of clinical
trials. Oxford: