- Email: [email protected]
Intercontinental fetal surgical consultation with image transmission via Internet
THE LANCET
Mean peripheral oxygen saturation measurements in 6 patients.
(Sp02)
The increasing availability of pulse oximetry in intensive care unitsz may lead to a false interpretation of oxygen transport capacity in cases of CO poisoning, especially if Sp02 is between 91 % and 98%. Physicians should be aware that the diagnosis of CO poisoning still depends on a high degree of clinical suspicion3and direct measurement of CO. D. SEIDLER M. M. HIRSCHL G. ROEGGLA
Emergency Department, General Hospital AKH, Vienna 1090, Austria
1. Tremper KK, Barker SJ. Pulse Oximetry. Anesthesiology 1989; 70: 98-108. 2. Schmidt H, Böhrer H, Bach A. Stellenwert des pulsoximetrischen monitoring in der intensivmedizin. Intens Notfallmed 1992; 17: 107-10. 3. Reisdorf EJ, Wiegenstein JG. Carbon monoxide poisoning. In: Tintinalli JE, Krome RL, Ruiz E, eds. Emergency medicine: a comprehensive study guide. New York: McGraw-Hill, 1992: 703-06.
Sudden infant death associated with defective oxidative phosphorylation SIR,-Sudden infant death preceeded by a fulminant hepatocellular disease has been described in children with inborn errors of mitochondrial fatty acid oxidation, such as medium-chain acylCoA dehydrogenase deficiency.Until now there have been few reports on hepatic failure caused by disorders of mitochondrial oxidative phosphorylation .2-3 The patient described by Boustany et al2 had a cytochrome c oxidase deficiency and a long illness before she eventually died of peritonitis. The neonates described by Cormier et al,3 also with cytochrome c oxidase deficiency, had liver disease associated with repeated episodes of ketoacidotic coma. We report a formerly healthy boy who suddenly died at 11 months after a Reye-like syndrome. His older sister had died at the age of 6 months after
identical clinical course. The boy was screened for inborn errors, with negative results. His medical history was unremarkable until the day before admission. Early in the afternoon, he became ill with fever and vomiting, and refused feeding. A general practitioner diagnosed otitis media and prescribed nose-drops. At 2300 h the boy was in a deep sleep and could hardly be awakened. Next morning he was found comatose and taken
mmol/L),
an
hospital. There was severe hypoglycaemia (07 moderately increased lactate (2-4 mmol/L), normal
with
1601
corresponding COHb values for 18
(130 JIDlol/L), and hyperammonaemia (240 µmol/L). Hypoglycaemia was corrected and artificial ventilation started, and he was brought to our clinic. The liver was enlarged by 2-3 cm. Neurological examination showed irritability, opisthotonos, and hypotonia. Examination of the urine showed an abnormal, but transient excretion of dicarboxylic and hydroxy-dicarboxylic acids with only slightly increased ketone body concentrations. Intravenous glucose administration (8 mg/kg per h) was continued and riboflavin also given. During the next few hours, he had multiple convulsions. Treatment was stopped after the electroencephalogram was found to be iso-electric. Necropsy was pyruvate
done within an hour of death. The liver showed marked steatosis. Investigation of the fatty acid oxidative capacity in muscle and liver was normal. Finally, we determined the activities of the respiratory chain enzymes in skeletal muscle. The results were compatible with a mitochondrial oxidative phosphorylation disorders caused by a defect in the coenzyme Q region of the respiratory chain (table). Most probably the boy’s sister had the same biochemical defect. At necropsy, she had the same abnormalities, although the activities of respiratory chain enzymes were not examined. Routine metabolic screening of urine does not fully guarantee the absence of an oxidative phosphorylation disorder.
J. A. M. SMEITINK J. C. FISCHER University Children’s Hospital, 3512 LK Utrecht, Netherlands; University Hospital Nijmegen; and Juliana Hospital, Apeldoorn
W. RUITENBEEK M. DURAN M. HOFKAMP H. A. J. M. BENTLAGE B. T. POLL-THE
1. Duran M, Hofkamp M, Rhead WJ, Saudubray JM, Wadman SK. Familial sudden child death and "healthy sibs" in a family with medium-chain acylCoA dehydrogenase deficiency leading to hypoketotic hypoglycemia and dicarboxylic adduria. Pediatric 1986; 78: 1052-57. 2. Boustany RN, Aprille JR, Halperin J, Levy H, DeLong GR. Mitochondrial cytochrome deficiency presenting as a myopathy with hypotonia, external ophthalmoplegia, and lactic acidosis in an infant and as fatal hepatopathy in a second cousin. Ann Neurol 1983; 14: 462-70. 3. Cormier V, Rustin P, Bonnefont J-P, et al. Hepatic failure in disorders of oxidative phosphorylanon with neonatal onset. J Pediatr 1991; 119: 951-54.
to a
ENZYME ACTIVITIES OF SKELETAL MUSCLE
NADH=nicotinamide
Values are mU per mg supernatant protein. adenine dinucleotide, reduced form, Q, = ubiquinol, C. = respiratory chain complex.
Intercontinental fetal surgical consultation with image transmission via Internet SIR,—Fetal surgery is not available in many countries, including the UK. We used the international computer network, Internet, to transmit ultrasound images of a fetus in London to the Fetal Treatment Program in San Francisco for a surgical opinion. A large echogenic right lung lesion was detected on ultrasound in a hydropic fetus at 20 weeks. The mixed solid and cystic appearance suggested the macrocystic type of cystic adenomatoid malformation (CAM), which was confirmed by needle biopsy. The lesion occupied 80% of the chest cavity, causing mediastinal shift and contralateral lung compression. Cyst drainage, by aspiration and by cyst-amniotic shunt placement’ made little difference to the hydrops or lesion size by 23 weeks. The mother was advised that the fetus was highly unlikely to survivethat no further treatment could
1602
THE LANCET
be offered in the UK, and that experimental fetal surgery for CAM associated with hydrops3 had promising results (current survival 5 out of 8), but could only be done in San Francisco and was associated with inconvenience and risk to herself. After counselling, she opted for fetal surgery. High-resolution ultrasound (Acuson XP10) was done in the evening UK time. Representative images were acquired by a video-capture card fitted to a personal computer at a resolution of about 512 x 512 pixels with 256 grey levels. The images were transferred to a larger computer and converted to a standard image format (GIF). With the file transfer protocol (FTP), the UK academic network JANET and Internet were used to transfer the images from London to San Francisco. Surgeons and radiologists from the team in San Francisco reviewed the images, and telephoned within the hour to speak to the referring physicians and the patient. Although the lesion was suitable for excision, they felt that the associated placentomegaly indicated a high risk of the mother developing the "mirror syndrome", 3,4 which not only puts the mother at risk but also negates the point of the surgery if delivery is indicated for maternal reasons. The mother was thus spared the expense and anxiety of an unnecessary transatlantic trip. Worldwide, only a few centres have the skill, experience, and facilities for open surgery in utero. Given the increasing availability of communications by new technology, international data transfer and consultation should become more widely used in all branches of medicine. Fetal Medicine Unit, Institute of Obstetrics and Gynaecology, Royal Postgraduate Medical School, Queen Charlotte’s and Chelsea Hospital, London W6 OXG, UK
NICHOLAS M. FISK JANET I. VAUGHAN
Department of Medical Physics, Royal Postgraduate Medical School, Hammersmith Hospital, London W12
RICHARD WOOTTON
Department of Surgery, Fetal Treatment Program, University of California, San Francisco, USA
MICHAEL R. HARRISON
1. Clark SL, Vitale DJ, Minton SD, Stoddard RA, Sabey PL. Successful fetal therapy for cystic adenomatoid malformation associated with second-trimester hydrops. Am J Obstet Gynecol 1987; 157: 294-95. 2. Adzick NS, Harrison MR, Glick PL, et al. Fetal cystic adenomatoid malformation: prenatal diagnosis and natural history. J Pediatr Surg 1985; 20: 483-88. 3. Harrison MR, Adzick NS, Jennings RW, et al. Antenatal intervention for congenital cystic malformation. Lancet 1990; 336: 965-67.
4. Langer JC, Harrison MR, Scmidt KG, et al. Fetal hydrops and death from sacroccygeal teratoma: rationale for fetal surgery. Am J Obstet Gynecol 1989; 160: 1145-50.
Triazolam safety SIR,-Dr Jonas of Upjohn (May 1, p 1150) claims that my summary of the FDA Psychopharmacologic Drugs Advisory Committee meeting on triazolam was highly selective. The FDA did not ban the drug, but it did find the 0-5 mg dose excessive and had safety concerns about 0-25 mg. All the FDA reservations and warnings occurred despite in-house differences of opinion about triazolam’s safety. The FDA Division of Epidemiology and Surveillance has consistently held over the past six years that triazolam produces many more and more severe psychiatric adverse reactions than comparable benzodiazepines. The Division of Neuropharmacologic Drug Products disagree; but this group was responsible for originally approving the use of the 0 5 mg dose in the USA, over the objections of the FDA’s own monitors. In 1988, following the ban on the 0-5 mg dose form in France, Italy, and West Germany, the FDA allowed Upjohn to reduce their recommended starting dose to 0-25 mg. In 1989, on the basis of data from its Division of Epidemiology and Surveillance, the FDA required stronger warnings, stating that triazolam presented a greater risk of anterograde amnesia than most other benzodiazepines. In 1991 and 1992, the FDA emphasised the need for very short-term use and the fact that even 0-25 mg produced significantly more daytime anxiety than comparison drug or placebo. By contrast, R. H. B. Conacher of Upjohn Ltd has stated that in clinical trials various behavioural side-effects such as
"occurred in patients receiving placebo at a rate indistinguishable from that in patients receiving Haldon". Perhaps it is Upjohn that is being highly selective regarding evidence on serious psychiatric reactions to triazolam.
nervousness
Department of Psychiatry, Autonomous University of Madrid, School of Medicine, 28008 Madrid, Spain
ANTONIO VELA-BUENO
SIR,-Dr Jonas questions the documentation in our petition to the FDA arguing that triazolam’s benefit-to-risk ratio is inadequate. Of the 157 references in that petition, 108 are specifically cited to a document. These include: 30 controlled studies, by sixteen different investigator groups; 13 controlled studies indicating limited efficacy for 0-25 mg of triazolam; 50 case-reports; 8 reports of postmarketing surveillance data; and 11published reports of laboratory evidence on triazolam’s safety problems. These 108 references do not include 4 references in the petition that constitute meta-analyses or reviews of different aspects of triazolam’s adverse reactions, to which Jonas refers misleadingly as "replications of the same study by Kales." Jonas also states that "equipotent doses of triazolam and other hypnotics show that triazolam does not produce more amnesia or behavioural medical events than other benzodiazepines.However, the controlled studies we cited compared doses of benzodiazepines that were equipotent both in regard to efficacy and to the starting recommended doses proposed by the respective manufacturer and approved by the FDA. Upjohn’s treatment, over the years as adverse reaction reports have accumulated, of the starting dosage recommendations for triazolam is instructive. Upjohn first introduced triazolam in 1977 at a recommended starting dose of up to 10 mg. After the Netherlands’ 1980 ban, Upjohn lowered the starting dose to 0-5 mg. When France, Italy, and West Germany banned the 0-5 mg tablet, Upjohn again reduced the dose worldwide to 0-25 mg. Even this has proved unacceptable in several countries, including the UK (ban) and France and Spain (reduction to 0-125 mg). There have been sixteen drug regulatory actions worldwide against triazolam since 1980 aimed at the manufacturer’s recommended doses. Every time Upjohn denied the safety concerns yet subsequently reduced the dose. Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
ANTHONY KALES EDWARD O. BIXLER ALEXANDROS N. VGONTZAS
Antistreptokinase titres after topical streptokinase SIR,—In 1990, Jalihal and Morris reported the results of a study showing a positive antibody response to a single intravenous dose of streptokinase.’ The increased use of thrombolytic agents after myocardial infarction has resulted in numerous patients being exposed to streptokinase and antistreplase. Re-exposure to these agents is not recommended within a cetain time because of the high antibody level and the risk of anaphylaxis. To see if topical streptokinase, as in "Varidase" (streptokinase and streptodornase) could be absorbed from a wound site and produce a similar response I measured anti-streptokinase titres in patients with wounds. The patients were monitored for any streptococcal infections during sampling, but no attempt was made to measure the amount of streptokinase absorbed. The amount used per treatment, number of treatments, type, and condition of the wound are shown in the table. Dr Jalihal did the antistreptokinase tests and the results are DETAILS OF STUDY PATIENTS
Mean peripheral oxygen saturation measurements in 6 patients.
(Sp02)
The increasing availability of pulse oximetry in intensive care unitsz may lead to a false interpretation of oxygen transport capacity in cases of CO poisoning, especially if Sp02 is between 91 % and 98%. Physicians should be aware that the diagnosis of CO poisoning still depends on a high degree of clinical suspicion3and direct measurement of CO. D. SEIDLER M. M. HIRSCHL G. ROEGGLA
Emergency Department, General Hospital AKH, Vienna 1090, Austria
1. Tremper KK, Barker SJ. Pulse Oximetry. Anesthesiology 1989; 70: 98-108. 2. Schmidt H, Böhrer H, Bach A. Stellenwert des pulsoximetrischen monitoring in der intensivmedizin. Intens Notfallmed 1992; 17: 107-10. 3. Reisdorf EJ, Wiegenstein JG. Carbon monoxide poisoning. In: Tintinalli JE, Krome RL, Ruiz E, eds. Emergency medicine: a comprehensive study guide. New York: McGraw-Hill, 1992: 703-06.
Sudden infant death associated with defective oxidative phosphorylation SIR,-Sudden infant death preceeded by a fulminant hepatocellular disease has been described in children with inborn errors of mitochondrial fatty acid oxidation, such as medium-chain acylCoA dehydrogenase deficiency.Until now there have been few reports on hepatic failure caused by disorders of mitochondrial oxidative phosphorylation .2-3 The patient described by Boustany et al2 had a cytochrome c oxidase deficiency and a long illness before she eventually died of peritonitis. The neonates described by Cormier et al,3 also with cytochrome c oxidase deficiency, had liver disease associated with repeated episodes of ketoacidotic coma. We report a formerly healthy boy who suddenly died at 11 months after a Reye-like syndrome. His older sister had died at the age of 6 months after
identical clinical course. The boy was screened for inborn errors, with negative results. His medical history was unremarkable until the day before admission. Early in the afternoon, he became ill with fever and vomiting, and refused feeding. A general practitioner diagnosed otitis media and prescribed nose-drops. At 2300 h the boy was in a deep sleep and could hardly be awakened. Next morning he was found comatose and taken
mmol/L),
an
hospital. There was severe hypoglycaemia (07 moderately increased lactate (2-4 mmol/L), normal
with
1601
corresponding COHb values for 18
(130 JIDlol/L), and hyperammonaemia (240 µmol/L). Hypoglycaemia was corrected and artificial ventilation started, and he was brought to our clinic. The liver was enlarged by 2-3 cm. Neurological examination showed irritability, opisthotonos, and hypotonia. Examination of the urine showed an abnormal, but transient excretion of dicarboxylic and hydroxy-dicarboxylic acids with only slightly increased ketone body concentrations. Intravenous glucose administration (8 mg/kg per h) was continued and riboflavin also given. During the next few hours, he had multiple convulsions. Treatment was stopped after the electroencephalogram was found to be iso-electric. Necropsy was pyruvate
done within an hour of death. The liver showed marked steatosis. Investigation of the fatty acid oxidative capacity in muscle and liver was normal. Finally, we determined the activities of the respiratory chain enzymes in skeletal muscle. The results were compatible with a mitochondrial oxidative phosphorylation disorders caused by a defect in the coenzyme Q region of the respiratory chain (table). Most probably the boy’s sister had the same biochemical defect. At necropsy, she had the same abnormalities, although the activities of respiratory chain enzymes were not examined. Routine metabolic screening of urine does not fully guarantee the absence of an oxidative phosphorylation disorder.
J. A. M. SMEITINK J. C. FISCHER University Children’s Hospital, 3512 LK Utrecht, Netherlands; University Hospital Nijmegen; and Juliana Hospital, Apeldoorn
W. RUITENBEEK M. DURAN M. HOFKAMP H. A. J. M. BENTLAGE B. T. POLL-THE
1. Duran M, Hofkamp M, Rhead WJ, Saudubray JM, Wadman SK. Familial sudden child death and "healthy sibs" in a family with medium-chain acylCoA dehydrogenase deficiency leading to hypoketotic hypoglycemia and dicarboxylic adduria. Pediatric 1986; 78: 1052-57. 2. Boustany RN, Aprille JR, Halperin J, Levy H, DeLong GR. Mitochondrial cytochrome deficiency presenting as a myopathy with hypotonia, external ophthalmoplegia, and lactic acidosis in an infant and as fatal hepatopathy in a second cousin. Ann Neurol 1983; 14: 462-70. 3. Cormier V, Rustin P, Bonnefont J-P, et al. Hepatic failure in disorders of oxidative phosphorylanon with neonatal onset. J Pediatr 1991; 119: 951-54.
to a
ENZYME ACTIVITIES OF SKELETAL MUSCLE
NADH=nicotinamide
Values are mU per mg supernatant protein. adenine dinucleotide, reduced form, Q, = ubiquinol, C. = respiratory chain complex.
Intercontinental fetal surgical consultation with image transmission via Internet SIR,—Fetal surgery is not available in many countries, including the UK. We used the international computer network, Internet, to transmit ultrasound images of a fetus in London to the Fetal Treatment Program in San Francisco for a surgical opinion. A large echogenic right lung lesion was detected on ultrasound in a hydropic fetus at 20 weeks. The mixed solid and cystic appearance suggested the macrocystic type of cystic adenomatoid malformation (CAM), which was confirmed by needle biopsy. The lesion occupied 80% of the chest cavity, causing mediastinal shift and contralateral lung compression. Cyst drainage, by aspiration and by cyst-amniotic shunt placement’ made little difference to the hydrops or lesion size by 23 weeks. The mother was advised that the fetus was highly unlikely to survivethat no further treatment could
1602
THE LANCET
be offered in the UK, and that experimental fetal surgery for CAM associated with hydrops3 had promising results (current survival 5 out of 8), but could only be done in San Francisco and was associated with inconvenience and risk to herself. After counselling, she opted for fetal surgery. High-resolution ultrasound (Acuson XP10) was done in the evening UK time. Representative images were acquired by a video-capture card fitted to a personal computer at a resolution of about 512 x 512 pixels with 256 grey levels. The images were transferred to a larger computer and converted to a standard image format (GIF). With the file transfer protocol (FTP), the UK academic network JANET and Internet were used to transfer the images from London to San Francisco. Surgeons and radiologists from the team in San Francisco reviewed the images, and telephoned within the hour to speak to the referring physicians and the patient. Although the lesion was suitable for excision, they felt that the associated placentomegaly indicated a high risk of the mother developing the "mirror syndrome", 3,4 which not only puts the mother at risk but also negates the point of the surgery if delivery is indicated for maternal reasons. The mother was thus spared the expense and anxiety of an unnecessary transatlantic trip. Worldwide, only a few centres have the skill, experience, and facilities for open surgery in utero. Given the increasing availability of communications by new technology, international data transfer and consultation should become more widely used in all branches of medicine. Fetal Medicine Unit, Institute of Obstetrics and Gynaecology, Royal Postgraduate Medical School, Queen Charlotte’s and Chelsea Hospital, London W6 OXG, UK
NICHOLAS M. FISK JANET I. VAUGHAN
Department of Medical Physics, Royal Postgraduate Medical School, Hammersmith Hospital, London W12
RICHARD WOOTTON
Department of Surgery, Fetal Treatment Program, University of California, San Francisco, USA
MICHAEL R. HARRISON
1. Clark SL, Vitale DJ, Minton SD, Stoddard RA, Sabey PL. Successful fetal therapy for cystic adenomatoid malformation associated with second-trimester hydrops. Am J Obstet Gynecol 1987; 157: 294-95. 2. Adzick NS, Harrison MR, Glick PL, et al. Fetal cystic adenomatoid malformation: prenatal diagnosis and natural history. J Pediatr Surg 1985; 20: 483-88. 3. Harrison MR, Adzick NS, Jennings RW, et al. Antenatal intervention for congenital cystic malformation. Lancet 1990; 336: 965-67.
4. Langer JC, Harrison MR, Scmidt KG, et al. Fetal hydrops and death from sacroccygeal teratoma: rationale for fetal surgery. Am J Obstet Gynecol 1989; 160: 1145-50.
Triazolam safety SIR,-Dr Jonas of Upjohn (May 1, p 1150) claims that my summary of the FDA Psychopharmacologic Drugs Advisory Committee meeting on triazolam was highly selective. The FDA did not ban the drug, but it did find the 0-5 mg dose excessive and had safety concerns about 0-25 mg. All the FDA reservations and warnings occurred despite in-house differences of opinion about triazolam’s safety. The FDA Division of Epidemiology and Surveillance has consistently held over the past six years that triazolam produces many more and more severe psychiatric adverse reactions than comparable benzodiazepines. The Division of Neuropharmacologic Drug Products disagree; but this group was responsible for originally approving the use of the 0 5 mg dose in the USA, over the objections of the FDA’s own monitors. In 1988, following the ban on the 0-5 mg dose form in France, Italy, and West Germany, the FDA allowed Upjohn to reduce their recommended starting dose to 0-25 mg. In 1989, on the basis of data from its Division of Epidemiology and Surveillance, the FDA required stronger warnings, stating that triazolam presented a greater risk of anterograde amnesia than most other benzodiazepines. In 1991 and 1992, the FDA emphasised the need for very short-term use and the fact that even 0-25 mg produced significantly more daytime anxiety than comparison drug or placebo. By contrast, R. H. B. Conacher of Upjohn Ltd has stated that in clinical trials various behavioural side-effects such as
"occurred in patients receiving placebo at a rate indistinguishable from that in patients receiving Haldon". Perhaps it is Upjohn that is being highly selective regarding evidence on serious psychiatric reactions to triazolam.
nervousness
Department of Psychiatry, Autonomous University of Madrid, School of Medicine, 28008 Madrid, Spain
ANTONIO VELA-BUENO
SIR,-Dr Jonas questions the documentation in our petition to the FDA arguing that triazolam’s benefit-to-risk ratio is inadequate. Of the 157 references in that petition, 108 are specifically cited to a document. These include: 30 controlled studies, by sixteen different investigator groups; 13 controlled studies indicating limited efficacy for 0-25 mg of triazolam; 50 case-reports; 8 reports of postmarketing surveillance data; and 11published reports of laboratory evidence on triazolam’s safety problems. These 108 references do not include 4 references in the petition that constitute meta-analyses or reviews of different aspects of triazolam’s adverse reactions, to which Jonas refers misleadingly as "replications of the same study by Kales." Jonas also states that "equipotent doses of triazolam and other hypnotics show that triazolam does not produce more amnesia or behavioural medical events than other benzodiazepines.However, the controlled studies we cited compared doses of benzodiazepines that were equipotent both in regard to efficacy and to the starting recommended doses proposed by the respective manufacturer and approved by the FDA. Upjohn’s treatment, over the years as adverse reaction reports have accumulated, of the starting dosage recommendations for triazolam is instructive. Upjohn first introduced triazolam in 1977 at a recommended starting dose of up to 10 mg. After the Netherlands’ 1980 ban, Upjohn lowered the starting dose to 0-5 mg. When France, Italy, and West Germany banned the 0-5 mg tablet, Upjohn again reduced the dose worldwide to 0-25 mg. Even this has proved unacceptable in several countries, including the UK (ban) and France and Spain (reduction to 0-125 mg). There have been sixteen drug regulatory actions worldwide against triazolam since 1980 aimed at the manufacturer’s recommended doses. Every time Upjohn denied the safety concerns yet subsequently reduced the dose. Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
ANTHONY KALES EDWARD O. BIXLER ALEXANDROS N. VGONTZAS
Antistreptokinase titres after topical streptokinase SIR,—In 1990, Jalihal and Morris reported the results of a study showing a positive antibody response to a single intravenous dose of streptokinase.’ The increased use of thrombolytic agents after myocardial infarction has resulted in numerous patients being exposed to streptokinase and antistreplase. Re-exposure to these agents is not recommended within a cetain time because of the high antibody level and the risk of anaphylaxis. To see if topical streptokinase, as in "Varidase" (streptokinase and streptodornase) could be absorbed from a wound site and produce a similar response I measured anti-streptokinase titres in patients with wounds. The patients were monitored for any streptococcal infections during sampling, but no attempt was made to measure the amount of streptokinase absorbed. The amount used per treatment, number of treatments, type, and condition of the wound are shown in the table. Dr Jalihal did the antistreptokinase tests and the results are DETAILS OF STUDY PATIENTS