254
tested again for HBV serum markers. A serum sample from donor (26-year-old man) proved positive for HBsAb and HBcAb. He had been admitted to a nearby hospital because of liver function abnormalities two months after he gave blood. The hospital record clearly showed that he had contracted typical acute hepatitis B infection. These findings show that, as predicted,2 post-transfusion fulminant hepatitis B infection can occur even after the introduction of blood screening for high-titre HBcAb, through blood from donors who, although acutely infected with HBV, are both HBsAg and HBcAb negative at the time of donation. were
one
M. YOSHIBA K. SEKIYAMA F. SUGATA
Division of Gastroenterology, Showa University Fujigaoka Hospital, Midori-Ku, Yokohama 227, Japan
Y. KAWAMOTO
H. MURAOKA M. AOYAMA
Japanese Red Cross, Kawasaki Blood Centre
M, Yamada H, Yoshikawa Y, et al. Hemodiafiltration treatment of deep hepatic coma by protein passing membrane case report. Artif Organs 1986; 10:
1. Yoshiba
used since it was prepared by Distillers Biochemicals from penicillin which, on hydrolysis, yields the D isomer only. In the United States penicillamine for clinical trials was synthesised from D,L-valine and the D and L forms were not separated, hence the case of optic neuritis described by Tu et al.’ After this report D,L-penicillamine was withdrawn and now only the D isomer is available. However, even D-penicillamine can mimic the antipyridoxine action of the L isomer if given in large doses and under certain specific circumstances such as pregnancy or during a growth spurt.4 In 1991 a case of optic neuritis induced by D-penicillamine was reported.s Kean et al seem to imply that the penicillamine-copper chelate is a simple 2-to-lI combination. The evidence suggests many penicillamine molecules binding copper (I) and (II) in a ratio of 14 to 12, though it does not follow that the chelate formed in vitro is was
that which occurs in vivo,7 where other aminoacids and albumin may be involved. Department of Neurology, Middlesex Hospital, London W1 N 8AA, UK
J. M. WALSHE
417-21. 2.
Hoofnagle JH. Editorial: posttransfusion hepatitis B Transfusion 1990; 30:
384-86.
Cyclosporin and muscle SIR,-Arellano and Krupp/ in their review of muscle disorders associated with cyclosporin, referred to three cases of possible muscular toxicity published by our group in 1989.2 In the table they state that biopsy was not done in two of our patients and that all had received prednisone. This is incorrect. Our report noted that biopsy, with examination by electronmicroscopy, was done in all cases, and all three had abnormalities. Moreover prednisone had been discontinued several months before myopathy developed. The statement that electromyograms were normal in our three cases is not true either, since our first case had an abnormal electromyogram. Arellano and Krupp have not read our report carefully, and it is very regrettable that Sandoz’ drug monitoring centre shall have recorded incorrect information, with the risk of the possible myotoxicity of cyclosporin being underrated. Division of
Cardiology and Pathology, CHU Vaudois,
J.-J. GOY J. P. DERUAZ
1011 Lausanne, Switzerland 1. Arellano
F, Krupp
P. Muscular disorders associated with
cyclosporin
Lancet 1991;
337: 915 2.
Goy JJ, Stauffer SC, Deruaz JP, et al. Myopathy cyclosporin. Lancet 1989, i: 1446-47.
as a
possible side-effect of
***This letter has been shown to Dr Arellano and Professor Krupp, reply follows.-ED. L. SIR,-We regret the misquotation of Dr Goy and colleagues’ report. Despite this oversight, we feel that the conclusions in our letter were not inappropriate. Indeed, our review has resulted in amendments to international product information on ’Sandimmun’. Myopathy is now mentioned as a side-effect and colchicine and lovastatin are noted as possible drug interactions leading to muscular toxicity. It was never our intention to underrate the myotoxicity of cyclosporin.
whose
Drug Monitoring Centre, Sandoz Pharma, 4002 Basle, Switzerland
F. ARELLANO P. KRUPP
Chirality of penicillamine SIR,-In their review on chirality and antirheumatic drugs Dr Kean and colleagues (Dec 21/28, p 1565) pay special attention to the D (or S) and the L (or R) enantiomers of penicillamine and refer to their work to illustrate optic neuritis induced by using D,L-penicillamine. That manifestation of L-penicillamine toxicity had been known since 1963/ and the original description of L-penicillamine toxicity can be traced back to the work of Wilson and Du Vigneaud in 1950/* In my 1956 article on the therapeutic potential of penicillamine for Wilson’s disease I stressed the differential toxicity of the D and L forms and recommended that the D form be used in clinical trials.’ In the UK D-penicillamine only
J-b, Blackwell RQ, Lee P-F. DL-penicillamine as a cause of optic axial neuritis JAMA 1963; 185: 83-86. 2. Wilson JE, Du Vigneaud V. Inhibition of growth in the rat by 1-penicillamine and its prevention by aminoethanol and related compounds J Biol Chem 1950; 312: 63-70. 3. Walshe JM. Penicillamine, a new oral therapy for Wilson’s disease Am J Med 1956, 1. Tu
21: 487-95. 4. Gibbs K, Walshe JM. Interruption of the tryptophan-nicotinic acid pathway by penicillamine induced pyridoxine deficiency in patients with Wilson’s disease and in experimental animals Ann NY Acad Sci 1969; 166: 158-69. 5. Lee A. Lawton NF. Penicillamine treatment of Wilson’s disease and optic neuropathy J Neurol Neurosurg Psychiatry 1991; 58: 746 6. Laurie SH, Prime DN. The formation and nature of the mixed valence copper-dpenicillamine-chloride cluster in aqueous solution and its relevance to the treatment of Wilson’s disease. J Inorgan Biochem 1979; 11: 229-39.
Two types of translucent membrane of caesarean section scar tissue SIR,-Pedowitz and Schwartz have reported that translucent membrane of transverse caesarean section scar tissue and incomplete uterine rupture occurred in 8-3% (22/266) patients at repeat caesarean section.’ We have graded findings at repeat caesarean section as follows: grade 1, neither thinning nor loss of continuity of lower uterine segment; grade II, thinning and loss of continuity but fetal hair not visible; grade III thinning or absence of lower uterine segment and fetal hair visible. The frequency of grade III was 9-1% (18/197) from September, 1982, until now 2-4 a frequency much the same as that recorded by Pedowitz and Schwartz. However, complete rupture of the lower transverse uterine scar is reported in 0-2-3% of planned trials of labour,s so what type of translucent membrane is it that ruptures during trials of labour-and can ultrasound scans distinguish one type from another? Since February, 1989, we have scanned 45 patients with previous caesarean section by high-resolution ultrasound (SSA-250A, Toshiba). 38 patients showed good healing with a thickness more than 1-2 mm throughout and 7 patients showed poor healing with reduced thickness and/or loss of continuity. Of 38 patients with good healing 10 were delivered vaginally and 28 patients had repeat caesarean section for other obstetric indications. Of 7 patients with poor healing 3 showed grade III operative findings (translucent membrane). The thinnest thickness of the lower uterine segment in these 3 patients near term by ultrasound is shown in the figure. Patient I showed great variability of thickness in the short term (5-10 min) and also over time (37-39 weeks) but patient III showed little variability (static thinning). Before repeat caesarean section in patient I thickness was never less than 0-5 mm and we predicted grade II; the thickness, by ophthalmic calipers, was 0-5 mm at operation. In patient III, with static thinning, thickness was 0-3 mm by ultrasound (7-5 MHz linear probe) before operation and 0-2 mm by ophthalmic calipers at operation. The thinnest portion of the lower uterine segment in patient I (variable thinning) showed good preservation of smooth muscle fibres and a little stromal fibrosis while that of the patient with static thinning showed prominent degeneration and atrophy of muscle fibres and severe stromal fibrosis with hyalinisation.
tested again for HBV serum markers. A serum sample from donor (26-year-old man) proved positive for HBsAb and HBcAb. He had been admitted to a nearby hospital because of liver function abnormalities two months after he gave blood. The hospital record clearly showed that he had contracted typical acute hepatitis B infection. These findings show that, as predicted,2 post-transfusion fulminant hepatitis B infection can occur even after the introduction of blood screening for high-titre HBcAb, through blood from donors who, although acutely infected with HBV, are both HBsAg and HBcAb negative at the time of donation. were
one
M. YOSHIBA K. SEKIYAMA F. SUGATA
Division of Gastroenterology, Showa University Fujigaoka Hospital, Midori-Ku, Yokohama 227, Japan
Y. KAWAMOTO
H. MURAOKA M. AOYAMA
Japanese Red Cross, Kawasaki Blood Centre
M, Yamada H, Yoshikawa Y, et al. Hemodiafiltration treatment of deep hepatic coma by protein passing membrane case report. Artif Organs 1986; 10:
1. Yoshiba
used since it was prepared by Distillers Biochemicals from penicillin which, on hydrolysis, yields the D isomer only. In the United States penicillamine for clinical trials was synthesised from D,L-valine and the D and L forms were not separated, hence the case of optic neuritis described by Tu et al.’ After this report D,L-penicillamine was withdrawn and now only the D isomer is available. However, even D-penicillamine can mimic the antipyridoxine action of the L isomer if given in large doses and under certain specific circumstances such as pregnancy or during a growth spurt.4 In 1991 a case of optic neuritis induced by D-penicillamine was reported.s Kean et al seem to imply that the penicillamine-copper chelate is a simple 2-to-lI combination. The evidence suggests many penicillamine molecules binding copper (I) and (II) in a ratio of 14 to 12, though it does not follow that the chelate formed in vitro is was
that which occurs in vivo,7 where other aminoacids and albumin may be involved. Department of Neurology, Middlesex Hospital, London W1 N 8AA, UK
J. M. WALSHE
417-21. 2.
Hoofnagle JH. Editorial: posttransfusion hepatitis B Transfusion 1990; 30:
384-86.
Cyclosporin and muscle SIR,-Arellano and Krupp/ in their review of muscle disorders associated with cyclosporin, referred to three cases of possible muscular toxicity published by our group in 1989.2 In the table they state that biopsy was not done in two of our patients and that all had received prednisone. This is incorrect. Our report noted that biopsy, with examination by electronmicroscopy, was done in all cases, and all three had abnormalities. Moreover prednisone had been discontinued several months before myopathy developed. The statement that electromyograms were normal in our three cases is not true either, since our first case had an abnormal electromyogram. Arellano and Krupp have not read our report carefully, and it is very regrettable that Sandoz’ drug monitoring centre shall have recorded incorrect information, with the risk of the possible myotoxicity of cyclosporin being underrated. Division of
Cardiology and Pathology, CHU Vaudois,
J.-J. GOY J. P. DERUAZ
1011 Lausanne, Switzerland 1. Arellano
F, Krupp
P. Muscular disorders associated with
cyclosporin
Lancet 1991;
337: 915 2.
Goy JJ, Stauffer SC, Deruaz JP, et al. Myopathy cyclosporin. Lancet 1989, i: 1446-47.
as a
possible side-effect of
***This letter has been shown to Dr Arellano and Professor Krupp, reply follows.-ED. L. SIR,-We regret the misquotation of Dr Goy and colleagues’ report. Despite this oversight, we feel that the conclusions in our letter were not inappropriate. Indeed, our review has resulted in amendments to international product information on ’Sandimmun’. Myopathy is now mentioned as a side-effect and colchicine and lovastatin are noted as possible drug interactions leading to muscular toxicity. It was never our intention to underrate the myotoxicity of cyclosporin.
whose
Drug Monitoring Centre, Sandoz Pharma, 4002 Basle, Switzerland
F. ARELLANO P. KRUPP
Chirality of penicillamine SIR,-In their review on chirality and antirheumatic drugs Dr Kean and colleagues (Dec 21/28, p 1565) pay special attention to the D (or S) and the L (or R) enantiomers of penicillamine and refer to their work to illustrate optic neuritis induced by using D,L-penicillamine. That manifestation of L-penicillamine toxicity had been known since 1963/ and the original description of L-penicillamine toxicity can be traced back to the work of Wilson and Du Vigneaud in 1950/* In my 1956 article on the therapeutic potential of penicillamine for Wilson’s disease I stressed the differential toxicity of the D and L forms and recommended that the D form be used in clinical trials.’ In the UK D-penicillamine only
J-b, Blackwell RQ, Lee P-F. DL-penicillamine as a cause of optic axial neuritis JAMA 1963; 185: 83-86. 2. Wilson JE, Du Vigneaud V. Inhibition of growth in the rat by 1-penicillamine and its prevention by aminoethanol and related compounds J Biol Chem 1950; 312: 63-70. 3. Walshe JM. Penicillamine, a new oral therapy for Wilson’s disease Am J Med 1956, 1. Tu
21: 487-95. 4. Gibbs K, Walshe JM. Interruption of the tryptophan-nicotinic acid pathway by penicillamine induced pyridoxine deficiency in patients with Wilson’s disease and in experimental animals Ann NY Acad Sci 1969; 166: 158-69. 5. Lee A. Lawton NF. Penicillamine treatment of Wilson’s disease and optic neuropathy J Neurol Neurosurg Psychiatry 1991; 58: 746 6. Laurie SH, Prime DN. The formation and nature of the mixed valence copper-dpenicillamine-chloride cluster in aqueous solution and its relevance to the treatment of Wilson’s disease. J Inorgan Biochem 1979; 11: 229-39.
Two types of translucent membrane of caesarean section scar tissue SIR,-Pedowitz and Schwartz have reported that translucent membrane of transverse caesarean section scar tissue and incomplete uterine rupture occurred in 8-3% (22/266) patients at repeat caesarean section.’ We have graded findings at repeat caesarean section as follows: grade 1, neither thinning nor loss of continuity of lower uterine segment; grade II, thinning and loss of continuity but fetal hair not visible; grade III thinning or absence of lower uterine segment and fetal hair visible. The frequency of grade III was 9-1% (18/197) from September, 1982, until now 2-4 a frequency much the same as that recorded by Pedowitz and Schwartz. However, complete rupture of the lower transverse uterine scar is reported in 0-2-3% of planned trials of labour,s so what type of translucent membrane is it that ruptures during trials of labour-and can ultrasound scans distinguish one type from another? Since February, 1989, we have scanned 45 patients with previous caesarean section by high-resolution ultrasound (SSA-250A, Toshiba). 38 patients showed good healing with a thickness more than 1-2 mm throughout and 7 patients showed poor healing with reduced thickness and/or loss of continuity. Of 38 patients with good healing 10 were delivered vaginally and 28 patients had repeat caesarean section for other obstetric indications. Of 7 patients with poor healing 3 showed grade III operative findings (translucent membrane). The thinnest thickness of the lower uterine segment in these 3 patients near term by ultrasound is shown in the figure. Patient I showed great variability of thickness in the short term (5-10 min) and also over time (37-39 weeks) but patient III showed little variability (static thinning). Before repeat caesarean section in patient I thickness was never less than 0-5 mm and we predicted grade II; the thickness, by ophthalmic calipers, was 0-5 mm at operation. In patient III, with static thinning, thickness was 0-3 mm by ultrasound (7-5 MHz linear probe) before operation and 0-2 mm by ophthalmic calipers at operation. The thinnest portion of the lower uterine segment in patient I (variable thinning) showed good preservation of smooth muscle fibres and a little stromal fibrosis while that of the patient with static thinning showed prominent degeneration and atrophy of muscle fibres and severe stromal fibrosis with hyalinisation.
