- Email: [email protected]
PNEUMOCYSTIS CARINII IN A HUSBAND AND WIFE
610
-
it is not true to say that a feature of the condition is the appearance of a new molecular type of collagen which is normally absent. However, the collagens of normal and rheumatoid synovia do appear to differ in their susceptibility to dissolution by pepsin treatment-a finding which may be related to an altered level of covalent crosslinking and rate of metabolism of collagen in the diseased tissue. Kennedy Institute of Rheumatology, Bute Gardens, London W6 7DW.
organism should arouse suspicion and lead to early investigation. The rapid resolution of the symptoms and signs of P. carinii pneumonitis in the wife following the institution of pentamidine isothionate reflects the clinical efficacy of this drug even in a patient with an underlying immunodepressive disease. Medical Oncology, University of Vermont Medical Center Hospital, Burlington, Vermont 05401, U.S.A. Department of Medicine, State University of New York at
D. R. EYRE HELEN MUIR.
PNEUMOCYSTIS CARINII IN A HUSBAND AND WIFE
Buffalo.
Department of Medicine B, Roswell Park Memorial Institute, 666 Elm Street, Buffalo,
SIR The epidemiology of Pneumocystis carinii infections
poorly understood.1 Its association with immunodepressive diseases in all age-groups is well established, and its epidemic potential has been appreciated in infants.2 Antibodies against P. carinii have been demonstrated in the parents of a child succumbing to a pneumocystis infection.3 We describe here a husband and wife, both with underlying hsematological malignancies, who in adults is
became colonised with P. carinii from one from the other.
a common source or
A 56-year-old man, successfully treated for multiple myeloma with cyclophosphamide and prednisone over a period of three years, developed acute monocytic leukaemia. For six months before the leukxmia was diagnosed, chemotherapy had been suspended because of the onset of unexplained leucopasnia. On admission the patient was in extremis with bilateral interstitial pneumonitis, and a bone-marrow aspirate demonstrated extensive leuka:mic infiltration. The patient died three days later and at necropsy was found to have P. carinii pneumonia. His 52-year-old wife was diagnosed as having a poorly differentiated nodular lymphocytic lymphoma four years before his death and at that time received mantle and right inguinal radiation therapy. Seven months after her husband’s death she was found to have recurrent disease in her cervical, periaortic, and left inguinal lymph-nodes. She was started on a course of nitrogen mustard and prednisone. Her tumour resolved completely, and she was placed on maintenance cyclophosphamide and prednisone. Eight months after her husband’s death she became febrile and weak and developed a dry cough, so her chemotherapy was discontinued. She failed to respond to antibiotic therapy and was treated with antifungal drugs followed by antituberculous antibiotics. Six months after the onset of her symptoms and a little over a year after her husband’s death, needle biopsy of her lung yielded P. carinii. The patient was then started on a twelve-day course of pentamidine isothionate (4 mg. per kg. daily) with a dramatic therapeutic response. Her pyrexia abated, she became energetic, and her bilateral interstitial pneumonitis cleared rapidly. She was again placed on maintenance chemotherapy for her underlying lymphoma, and she has remained well without evidence of infection or lymphoma. .
Suspicion remains the major factor in assuring proper diagnosis of P. carinii pneumonitis. The death of the husband should have aroused suspicion as to the aetiology of the wife’s infection, but a communication failure between attending physicians caused the delay in her diagnosis. Fortunately, this did not interfere with her successful treatment.
The occurrence of this rather unusual infection in a husband and wife suggests colonisation from a common source or one from the other, followed by an active infe’cWhen possible, immunosuppressed individuals tion. should be protected by isolating patients with active P. carinii infections, hopefully curbing contact colonisation. An awareness that close contacts may be colonised with this 1. 2. 3.
Walzer, P. D., Perl, D. P., Krogstad, D. J., Rawson, P. G., Schultz, M. G. Ann. intern. Med. 1974, 80, 83. Hughes, W. T., Price, R. A., Kim, H., Coburn, T. P., Grigsby, D., Feldman, S. J. Pediat. 1973, 82, 404. Meuwissen, H. J., Brzosko, W. J., Nowoslawski, A., Good, R. A. Lancet, 1970, i, 1124.
N.Y. 14203.
JEROME W. YATES. ROSE RUTH ELLISON.
JOHN PLAGER.
PREVENTION OF ACETAMINOPHEN (PARACETAMOL) POISONING
SIR,-Some authors 1-3 have reported on the intravenous of cysteamine and similar compounds as treatment for acetaminophen (paracetamol) overdose. Because of the possible side-effects from these treatments, McLean4 added methionine to acetaminophen and gave the mixture by gastric tube to rats pretreated with barbiturates. This use
addition of methionine raised the lethal dose of acetamino2 g. per kg. to over 5 g. per kg. We have investigated methionine’s efficacy in dogs. Serum-glutamic-pyruvic-transaminase (s.G.P.T.) and serum-
phen from
glutamic-oxalacetic-transaminase (S.G.o.T.) determinations proved to be more sensitive indicators of hepatic damage than bromsulphthalein, serum-alkaline-phosphatase, and serum-bilirubin. Prothrombin-time was also used, since it measured a different hepatic function. Blood-ureanitrogen (B.U.N.) was run as a check on renal function. 3 groups of 6 dogs were given, respectively, 750 mg. per kg. of acetaminophen, 750 mg. per kg. of acetaminophen plus 150 mg. per kg. of methionine, and 1000 mg. per kg. of acetaminophen plus 200 mg. per kg. of methionine as an aqueous slurry by stomach tube. S.G.P.T., S.G.O.T., B.U.N., and prothrombin-time were determined on serum samples from all dogs before dosing and all survivors 24, 48, and 72 hours later. These analyses were continued in the group receiving 1000 mg. per kg. of acetaminophen until all values returned to normal. Liver tissue was taken from the animals that died and wedge biopsies in 72 hours from all other dogs receiving either of the 750 mg. per kg. acetaminophen treatments.
During the 72-hour tests, 4 animals died-all in the acetaminogroup, 2 of them within 24 hours and 2 more by 48 hours. This group was also clearly separated from the two
phen-only
methionine-treated groups on the basis of their S.G.P.T. and S.G.o.T. levels and prothrombin-times. On the basis of hepatic histopathological changes, 4 of the dogs receiving 750 mg. per kg. of acetaminophen plus methionine clearly had less damage than the others. The damage seen in the other 2 dogs in this group could not be distinguished from those not protected by methionine. This lack of difference may have been due in part to the death in 4 of the dogs receiving only acetaminophen before more extensive damage could develop. One week after the dosing, the blood-chemistry values of the high-dose acetaminophen-methionine group were back to predosing levels in 4 of the 6 dogs. S.G.P.T. and s.G.o.T. in the other 2 dogs remained high (but falling) until the third week in 1 and the fourth week in the other before returning to control values. After general anaesthesia for the liver biopsy, 1 dog died from each of the groups receiving 750 mg. of acetaminophen. 1 of these died of kidney failure, and the other from the anaathesia. 1. 2. 3.
Mitchell, J. R., et al. J. Pharmac. exp. Ther. 1973, 187, 211. Mitchell, J. R., et al. Drug Metab. Disp. 1973, 1, 418. Prescott, L. F., Newton, R. W., Swainson, C. P., Wright, N., Forrest, A. R. W., Matthew, H. Lancet, 1974, i, 588.
4.
McLean, A. E. M. ibid.
p. 729.
-
it is not true to say that a feature of the condition is the appearance of a new molecular type of collagen which is normally absent. However, the collagens of normal and rheumatoid synovia do appear to differ in their susceptibility to dissolution by pepsin treatment-a finding which may be related to an altered level of covalent crosslinking and rate of metabolism of collagen in the diseased tissue. Kennedy Institute of Rheumatology, Bute Gardens, London W6 7DW.
organism should arouse suspicion and lead to early investigation. The rapid resolution of the symptoms and signs of P. carinii pneumonitis in the wife following the institution of pentamidine isothionate reflects the clinical efficacy of this drug even in a patient with an underlying immunodepressive disease. Medical Oncology, University of Vermont Medical Center Hospital, Burlington, Vermont 05401, U.S.A. Department of Medicine, State University of New York at
D. R. EYRE HELEN MUIR.
PNEUMOCYSTIS CARINII IN A HUSBAND AND WIFE
Buffalo.
Department of Medicine B, Roswell Park Memorial Institute, 666 Elm Street, Buffalo,
SIR The epidemiology of Pneumocystis carinii infections
poorly understood.1 Its association with immunodepressive diseases in all age-groups is well established, and its epidemic potential has been appreciated in infants.2 Antibodies against P. carinii have been demonstrated in the parents of a child succumbing to a pneumocystis infection.3 We describe here a husband and wife, both with underlying hsematological malignancies, who in adults is
became colonised with P. carinii from one from the other.
a common source or
A 56-year-old man, successfully treated for multiple myeloma with cyclophosphamide and prednisone over a period of three years, developed acute monocytic leukaemia. For six months before the leukxmia was diagnosed, chemotherapy had been suspended because of the onset of unexplained leucopasnia. On admission the patient was in extremis with bilateral interstitial pneumonitis, and a bone-marrow aspirate demonstrated extensive leuka:mic infiltration. The patient died three days later and at necropsy was found to have P. carinii pneumonia. His 52-year-old wife was diagnosed as having a poorly differentiated nodular lymphocytic lymphoma four years before his death and at that time received mantle and right inguinal radiation therapy. Seven months after her husband’s death she was found to have recurrent disease in her cervical, periaortic, and left inguinal lymph-nodes. She was started on a course of nitrogen mustard and prednisone. Her tumour resolved completely, and she was placed on maintenance cyclophosphamide and prednisone. Eight months after her husband’s death she became febrile and weak and developed a dry cough, so her chemotherapy was discontinued. She failed to respond to antibiotic therapy and was treated with antifungal drugs followed by antituberculous antibiotics. Six months after the onset of her symptoms and a little over a year after her husband’s death, needle biopsy of her lung yielded P. carinii. The patient was then started on a twelve-day course of pentamidine isothionate (4 mg. per kg. daily) with a dramatic therapeutic response. Her pyrexia abated, she became energetic, and her bilateral interstitial pneumonitis cleared rapidly. She was again placed on maintenance chemotherapy for her underlying lymphoma, and she has remained well without evidence of infection or lymphoma. .
Suspicion remains the major factor in assuring proper diagnosis of P. carinii pneumonitis. The death of the husband should have aroused suspicion as to the aetiology of the wife’s infection, but a communication failure between attending physicians caused the delay in her diagnosis. Fortunately, this did not interfere with her successful treatment.
The occurrence of this rather unusual infection in a husband and wife suggests colonisation from a common source or one from the other, followed by an active infe’cWhen possible, immunosuppressed individuals tion. should be protected by isolating patients with active P. carinii infections, hopefully curbing contact colonisation. An awareness that close contacts may be colonised with this 1. 2. 3.
Walzer, P. D., Perl, D. P., Krogstad, D. J., Rawson, P. G., Schultz, M. G. Ann. intern. Med. 1974, 80, 83. Hughes, W. T., Price, R. A., Kim, H., Coburn, T. P., Grigsby, D., Feldman, S. J. Pediat. 1973, 82, 404. Meuwissen, H. J., Brzosko, W. J., Nowoslawski, A., Good, R. A. Lancet, 1970, i, 1124.
N.Y. 14203.
JEROME W. YATES. ROSE RUTH ELLISON.
JOHN PLAGER.
PREVENTION OF ACETAMINOPHEN (PARACETAMOL) POISONING
SIR,-Some authors 1-3 have reported on the intravenous of cysteamine and similar compounds as treatment for acetaminophen (paracetamol) overdose. Because of the possible side-effects from these treatments, McLean4 added methionine to acetaminophen and gave the mixture by gastric tube to rats pretreated with barbiturates. This use
addition of methionine raised the lethal dose of acetamino2 g. per kg. to over 5 g. per kg. We have investigated methionine’s efficacy in dogs. Serum-glutamic-pyruvic-transaminase (s.G.P.T.) and serum-
phen from
glutamic-oxalacetic-transaminase (S.G.o.T.) determinations proved to be more sensitive indicators of hepatic damage than bromsulphthalein, serum-alkaline-phosphatase, and serum-bilirubin. Prothrombin-time was also used, since it measured a different hepatic function. Blood-ureanitrogen (B.U.N.) was run as a check on renal function. 3 groups of 6 dogs were given, respectively, 750 mg. per kg. of acetaminophen, 750 mg. per kg. of acetaminophen plus 150 mg. per kg. of methionine, and 1000 mg. per kg. of acetaminophen plus 200 mg. per kg. of methionine as an aqueous slurry by stomach tube. S.G.P.T., S.G.O.T., B.U.N., and prothrombin-time were determined on serum samples from all dogs before dosing and all survivors 24, 48, and 72 hours later. These analyses were continued in the group receiving 1000 mg. per kg. of acetaminophen until all values returned to normal. Liver tissue was taken from the animals that died and wedge biopsies in 72 hours from all other dogs receiving either of the 750 mg. per kg. acetaminophen treatments.
During the 72-hour tests, 4 animals died-all in the acetaminogroup, 2 of them within 24 hours and 2 more by 48 hours. This group was also clearly separated from the two
phen-only
methionine-treated groups on the basis of their S.G.P.T. and S.G.o.T. levels and prothrombin-times. On the basis of hepatic histopathological changes, 4 of the dogs receiving 750 mg. per kg. of acetaminophen plus methionine clearly had less damage than the others. The damage seen in the other 2 dogs in this group could not be distinguished from those not protected by methionine. This lack of difference may have been due in part to the death in 4 of the dogs receiving only acetaminophen before more extensive damage could develop. One week after the dosing, the blood-chemistry values of the high-dose acetaminophen-methionine group were back to predosing levels in 4 of the 6 dogs. S.G.P.T. and s.G.o.T. in the other 2 dogs remained high (but falling) until the third week in 1 and the fourth week in the other before returning to control values. After general anaesthesia for the liver biopsy, 1 dog died from each of the groups receiving 750 mg. of acetaminophen. 1 of these died of kidney failure, and the other from the anaathesia. 1. 2. 3.
Mitchell, J. R., et al. J. Pharmac. exp. Ther. 1973, 187, 211. Mitchell, J. R., et al. Drug Metab. Disp. 1973, 1, 418. Prescott, L. F., Newton, R. W., Swainson, C. P., Wright, N., Forrest, A. R. W., Matthew, H. Lancet, 1974, i, 588.
4.
McLean, A. E. M. ibid.
p. 729.