812
Khuroo and colleagues’ series, suggesting that women may in some way be more prone to the morbidity of intestinal helminthiasis, especially ascariasis. Department of Medicine, Hospital Universiti Sains Malaysia, 16150 Kubang Kerian, Kelatan, Malaysia
S. MAHENDRA RAJ SIVA SIVAKUMARAN S. VIJAYAKUMARI
Improved results with PCR for chronic myeloid leukaemia SIR,-We found a high frequency of false-positive results in a study in Europe and North America used the chain reaction (PCR) to look for leukaemia-specific polymerase bcrlabl transcripts in chronic myeloid leukaemia (CML) cell lines and negative controls.’ In a second study similar material was distributed to see whether false positives could be reduced and if the source of any contamination could be identified. Groups were asked to adhere to the precautions recommended by Kwok and Higushi2 and to run a standardised set of negative controls. Ten samples were distributed in two sets of five (batches A and B) prepared from leukaemia cell lines. In batch A two samples of undiluted bcrlabl positive material both contained the b2a2 transcript and three samples were ber/abl negative. In batch B three samples contained dilutions of cells with the b3a2 transcript into ber/ abl negative cells in ratios of 1 in 104 to 1 in 106, and two samples in which
were
ten centres
bcrlabl negative.
Seven groups
reported their results:
Material Undiluted positive Diluted positive
Negative
Correct result
Total 12 20 30
12 13 26
*Because PCR can amplify b2a2 theoretically be obtained
or
b3a2 mRNA,
False
False
positive
negative
0* 0 4
0 7 ..
false-positive results can
There was a striking reduction in false-positive and false-negative results. Three of the four false positives were for negative samples from batch A which included undiluted positive samples, and these positive samples may have cross-contaminated negative ones because the same b2a2 product was detected in all three. Only one false-positive result was seen in batch B, in which only dilute positive samples were included. False negatives were reported in six samples but in four of these cases the sample was at the highest dilution (1 in 106) of bcr/abl-positive cells and in each case the next lower dilution (1 in 105) at the same centre was correctly identified. Thus false positives can be kept to a minimum (but probably not eliminated) by adherence to standard precautions and by avoidance of the processing of undiluted positives with unknown samples. Contributors to this study were essentially the same as those for the first multicentre study. Additional contributors were Dr G. Martinelli (Verona) and Dr P. Richard (Paris).
Haematology Department, Royal Postgraduate Medical School, London W12 ONN, UK 1 2
TIMOTHY HUGHES JOHN M. GOLDMAN
Hughes TP, Janssen JWG, Morgan G, et al. False positive results with PCR to detect leukaemia-specific transcript. Lancet 1990; 335: 1037-38. Kwok S, Higuchi R. Avoiding false positives with PCR Nature 1989, 339: 237
Iodine-induced hypothyroidism in infants treated with continuous cyclic peritoneal
dialysis SIR,-An excessive intake of iodine can lead to hypothyroidism and goitre.’ In adults this has no serious consequences and is easily treatable; however, iodine intoxication in infants can cause severe damage, such as impaired psychomotor development due to longstanding hypothyroidism, or suffocation due to a congenital goitreGavin et aP reported two adults with iodine-induced hypothyroidism associated with continuous ambulatory peritoneal dialysis, apparently induced by excessive amounts of iodine resorbed from povidone-iodine-containing dialysate (although
Gardner et al4 have subsequently disagreed with this explanation), A striking feature was that serum T4 levels were only moderately decreased. Peritoneal dialysis, especially continuous cyclic peritoneal dialysis (CCPD), is used increasingly to treat very young infants. Although povidone-iodine is no longer used in dialysates, a povidone-iodine-containing cap is used to seal the Tenckhoff catheter during the day. Because young infants are at particular risk of iodine-induced hypothyroidism, since the Wolff-Chaikoff effect (ie, instantaneous inhibition of iodine organification) is not always followed by the "escape mechanism", we monitored thyroid function. We have since observed two cases that justify this policy, The first patient, a 3-year-old boy, had severe nephrotic syndrome and progressive loss of renal function due to glomerular sclerosis. A longstanding hypothyroidism due to excessive renal loss ofT4 resolved when he became anuric. Nevertheless, his plasma T4 level fell to 50 nmol/l, and plasma thyroid-stimulating hormone increased to 37 mU/1 shortly after peritoneal dialysis. A simultaneous increase of plasma thyroglobulin to 1300 pmoljl (normal 15-375 pmol/1) suggested defective thyroid hormone synthesis. Indeed, iodine organification seemed to be defective, as shown by a high radioiodide uptake and a 90% discharge of radioiodide after administration of perchlorate. The second patient, an 18-month-old girl, had bilateral Wilms’ tumours, mesangial sclerosis (Drash syndrome), and features of a severe nephrotic syndrome, including a T4-wasting type of hypothyroidism. After bilateral nephrectomy and the start of CCPD, plasma T4 dropped rapidly to 10 nmolfl with a simultaneous rise of plasma thyroidstimulating hormone to 2900 mU/1. The patient had high serum thyroglobulin (2300 pmol/1), a high radioiodide uptake, and 90% discharge after administration of perchlorate. In both cases the iodine source was shown to be the sealing cap of the Tenckhoff catheter. The iodine inside this cap diffused into the catheter and flushed into the peritoneal cavity at the next dialysis session.
of Experimental Paediatric Endocrinology, Academic Medical Centre, 1105 AZ Amsterdam, Netherlands
Department
THOMAS VULSMA DARIA MENZEL FILOMENA C. B. ABBAD MARGARETH H. GONS JAN J. M. DE VIJLDER
Trotter WR. Two cases of myxoedema attributed to iodide administration Lancet 1953; ii 1335-37 2 Galina MP, Avnet NL, Einhorn A. Iodides dunng pregnancy. an apparent cause of neonatal death N Engl JMed 1962; 267: 1124-27. 3 Gavin LA, Eitan NF, Cavalieri RR, Schmidt WR Hypothyroidism induced by continuous ambulatory peritoneal diaylisis. Western J Med 1983; 138: 562-65 4 Gardner DF, Mars DR, Thomas RG, Bumrungsup C, Misbin RI Iodine retention and thyroid dysfunction m patients on hemodialysis and continuous ambulatory peritoneal dialysis. Am J Kidney Dis 1986; 7: 471-76.
1 Morgans ME,
Polycythaemia and HIV infection SIR,-Dr Battan and colleagues describe a patient with AIDS and polycythaemia (June 2, p 1342). We have seen a similar patient who has presumed HIV disease but not AIDS. A 41-year-old homosexual man presented in September, 1988, with malaise, fever, night sweats, haematuria, and dysuria. He smoked 40 cigarettes per day and consumed 25 units of alcohol weekly. Examination showed plethora, leuconychia, angular stomatitis, oral candidosis and hairy leucoplakia, generalised lymphadenopathy, and a smooth 4 cm enlarged liver. Haemoglobin (Hb) was 20-0 g/dl, with a packed cell volume (PCV) of 062. In 1979 his Hb had been 143 gdl and in 1983 it was 17-8 gfdl. Gamma
glutamyltransferase and alkaline phosphate were raised at 118 and 169 units per litre, respectively, but later fell to normal. Resting and post-exercise arterial blood gases were within normal limits (pOz = 13kPa), and carboxyhaemoglobin was 6’ 1 %. There wasa mild obstructive ventilatory defect and moderate reduction in gas transfer. Repeat Hb was 21-3 g/dl, with a PCV of 0-64. Mean corpuscular volume was 109 fl, and white cell and platelet counts were normal. Bone-marrow aspiration showed early megaloblasdc changes and normal iron stores. Serum B12 was 96 ngfl and folate was 1-0 ug/1. (Because of his polycythaemia, treatment with Me
Khuroo and colleagues’ series, suggesting that women may in some way be more prone to the morbidity of intestinal helminthiasis, especially ascariasis. Department of Medicine, Hospital Universiti Sains Malaysia, 16150 Kubang Kerian, Kelatan, Malaysia
S. MAHENDRA RAJ SIVA SIVAKUMARAN S. VIJAYAKUMARI
Improved results with PCR for chronic myeloid leukaemia SIR,-We found a high frequency of false-positive results in a study in Europe and North America used the chain reaction (PCR) to look for leukaemia-specific polymerase bcrlabl transcripts in chronic myeloid leukaemia (CML) cell lines and negative controls.’ In a second study similar material was distributed to see whether false positives could be reduced and if the source of any contamination could be identified. Groups were asked to adhere to the precautions recommended by Kwok and Higushi2 and to run a standardised set of negative controls. Ten samples were distributed in two sets of five (batches A and B) prepared from leukaemia cell lines. In batch A two samples of undiluted bcrlabl positive material both contained the b2a2 transcript and three samples were ber/abl negative. In batch B three samples contained dilutions of cells with the b3a2 transcript into ber/ abl negative cells in ratios of 1 in 104 to 1 in 106, and two samples in which
were
ten centres
bcrlabl negative.
Seven groups
reported their results:
Material Undiluted positive Diluted positive
Negative
Correct result
Total 12 20 30
12 13 26
*Because PCR can amplify b2a2 theoretically be obtained
or
b3a2 mRNA,
False
False
positive
negative
0* 0 4
0 7 ..
false-positive results can
There was a striking reduction in false-positive and false-negative results. Three of the four false positives were for negative samples from batch A which included undiluted positive samples, and these positive samples may have cross-contaminated negative ones because the same b2a2 product was detected in all three. Only one false-positive result was seen in batch B, in which only dilute positive samples were included. False negatives were reported in six samples but in four of these cases the sample was at the highest dilution (1 in 106) of bcr/abl-positive cells and in each case the next lower dilution (1 in 105) at the same centre was correctly identified. Thus false positives can be kept to a minimum (but probably not eliminated) by adherence to standard precautions and by avoidance of the processing of undiluted positives with unknown samples. Contributors to this study were essentially the same as those for the first multicentre study. Additional contributors were Dr G. Martinelli (Verona) and Dr P. Richard (Paris).
Haematology Department, Royal Postgraduate Medical School, London W12 ONN, UK 1 2
TIMOTHY HUGHES JOHN M. GOLDMAN
Hughes TP, Janssen JWG, Morgan G, et al. False positive results with PCR to detect leukaemia-specific transcript. Lancet 1990; 335: 1037-38. Kwok S, Higuchi R. Avoiding false positives with PCR Nature 1989, 339: 237
Iodine-induced hypothyroidism in infants treated with continuous cyclic peritoneal
dialysis SIR,-An excessive intake of iodine can lead to hypothyroidism and goitre.’ In adults this has no serious consequences and is easily treatable; however, iodine intoxication in infants can cause severe damage, such as impaired psychomotor development due to longstanding hypothyroidism, or suffocation due to a congenital goitreGavin et aP reported two adults with iodine-induced hypothyroidism associated with continuous ambulatory peritoneal dialysis, apparently induced by excessive amounts of iodine resorbed from povidone-iodine-containing dialysate (although
Gardner et al4 have subsequently disagreed with this explanation), A striking feature was that serum T4 levels were only moderately decreased. Peritoneal dialysis, especially continuous cyclic peritoneal dialysis (CCPD), is used increasingly to treat very young infants. Although povidone-iodine is no longer used in dialysates, a povidone-iodine-containing cap is used to seal the Tenckhoff catheter during the day. Because young infants are at particular risk of iodine-induced hypothyroidism, since the Wolff-Chaikoff effect (ie, instantaneous inhibition of iodine organification) is not always followed by the "escape mechanism", we monitored thyroid function. We have since observed two cases that justify this policy, The first patient, a 3-year-old boy, had severe nephrotic syndrome and progressive loss of renal function due to glomerular sclerosis. A longstanding hypothyroidism due to excessive renal loss ofT4 resolved when he became anuric. Nevertheless, his plasma T4 level fell to 50 nmol/l, and plasma thyroid-stimulating hormone increased to 37 mU/1 shortly after peritoneal dialysis. A simultaneous increase of plasma thyroglobulin to 1300 pmoljl (normal 15-375 pmol/1) suggested defective thyroid hormone synthesis. Indeed, iodine organification seemed to be defective, as shown by a high radioiodide uptake and a 90% discharge of radioiodide after administration of perchlorate. The second patient, an 18-month-old girl, had bilateral Wilms’ tumours, mesangial sclerosis (Drash syndrome), and features of a severe nephrotic syndrome, including a T4-wasting type of hypothyroidism. After bilateral nephrectomy and the start of CCPD, plasma T4 dropped rapidly to 10 nmolfl with a simultaneous rise of plasma thyroidstimulating hormone to 2900 mU/1. The patient had high serum thyroglobulin (2300 pmol/1), a high radioiodide uptake, and 90% discharge after administration of perchlorate. In both cases the iodine source was shown to be the sealing cap of the Tenckhoff catheter. The iodine inside this cap diffused into the catheter and flushed into the peritoneal cavity at the next dialysis session.
of Experimental Paediatric Endocrinology, Academic Medical Centre, 1105 AZ Amsterdam, Netherlands
Department
THOMAS VULSMA DARIA MENZEL FILOMENA C. B. ABBAD MARGARETH H. GONS JAN J. M. DE VIJLDER
Trotter WR. Two cases of myxoedema attributed to iodide administration Lancet 1953; ii 1335-37 2 Galina MP, Avnet NL, Einhorn A. Iodides dunng pregnancy. an apparent cause of neonatal death N Engl JMed 1962; 267: 1124-27. 3 Gavin LA, Eitan NF, Cavalieri RR, Schmidt WR Hypothyroidism induced by continuous ambulatory peritoneal diaylisis. Western J Med 1983; 138: 562-65 4 Gardner DF, Mars DR, Thomas RG, Bumrungsup C, Misbin RI Iodine retention and thyroid dysfunction m patients on hemodialysis and continuous ambulatory peritoneal dialysis. Am J Kidney Dis 1986; 7: 471-76.
1 Morgans ME,
Polycythaemia and HIV infection SIR,-Dr Battan and colleagues describe a patient with AIDS and polycythaemia (June 2, p 1342). We have seen a similar patient who has presumed HIV disease but not AIDS. A 41-year-old homosexual man presented in September, 1988, with malaise, fever, night sweats, haematuria, and dysuria. He smoked 40 cigarettes per day and consumed 25 units of alcohol weekly. Examination showed plethora, leuconychia, angular stomatitis, oral candidosis and hairy leucoplakia, generalised lymphadenopathy, and a smooth 4 cm enlarged liver. Haemoglobin (Hb) was 20-0 g/dl, with a packed cell volume (PCV) of 062. In 1979 his Hb had been 143 gdl and in 1983 it was 17-8 gfdl. Gamma
glutamyltransferase and alkaline phosphate were raised at 118 and 169 units per litre, respectively, but later fell to normal. Resting and post-exercise arterial blood gases were within normal limits (pOz = 13kPa), and carboxyhaemoglobin was 6’ 1 %. There wasa mild obstructive ventilatory defect and moderate reduction in gas transfer. Repeat Hb was 21-3 g/dl, with a PCV of 0-64. Mean corpuscular volume was 109 fl, and white cell and platelet counts were normal. Bone-marrow aspiration showed early megaloblasdc changes and normal iron stores. Serum B12 was 96 ngfl and folate was 1-0 ug/1. (Because of his polycythaemia, treatment with Me
