307
function before such losses occur must be preferable, and this can be achieved only if an accurate and reproducible method of determining renal function is used to monitor patients with potentially progressive disease. To this end, clinicians have most 24 h creatinine clearance. This has been be inaccurate but also of poor repeatability with figures for reproducibility of 20% and 30% .’* Its role in monitoring function has to be seen as questionable. In contrast, plasma clearance measurements of filtration markers such as 51Cr-EDT A have a reproducibility of 3-5 %, probably the best that can be achieved, allowing for physiological variation.45 Such methods are rarely used for objective clinical monitoring because they are time-consuming, the availability of nuclear medicine skills is limited, and repeated injection of radiopharmaceuticals should be avoided. Into the area comes the non-ionic contrast medium iohexol, which, it is suggested, might be considered as an alternative to inulin clearance, widely regarded as the "gold standard". There are of course no "24 carat gold" standards for GFR. Iohexol has the same excretory properties as inulin but none of the handling problems of that rather insoluble and unstable polysaccharide; and it is not a radiopharmaceutical. At the low doses possible for clearance studies iohexol is free of the dose-related adverse effects attributable to contrast media. Assay has been made simple by the implementation of X-ray radiofluorescence analysis.’1 Since iohexol is an ordinary radiographic contrast, GFR measurement can accompany any intravascular contrast examination. We believe that the technique offers considerable potential for increased detection and objective monitoring of renal impairment and that it is an important advance.
commonly adopted the
shown not only to
Department of Urology, Stepping Hill Hospital,
Stockport SK2 7JE,UK
STEPHEN BROWN
1 Brown
SCW, O’Reilly PH. Iohexol clearance for the determination of glomerular filtration rate in clinical practice: evidence for a new gold standard. J Urol 1991; 146:
675-79. 2. Gabnel R. Time to scrap creatinine clearance? Br Med 1986; 293: 1119-20. J 3. Dodge WF, Travis LD, Daeschner CW. Comparison of endogenous creatinine clearance with inulin clearance. Am J Dis Child 1967; 113: 683-92 4. Brochner-Mortensen J, Rodbro P. Selection of routine method for determination of glomerular filtration rate in adult patients. Scand J Clin Lab Inv 1976; 36: 35-42. 5. Chantler C, Barratt TM. Estimation of glomerular filtration rate from plasma clearance of 51Cr-EDTA. Arch Dis Child 1972; 47: 613-17
Duration of efficacy of anti-anginal
drugs
SIR,-The discussion (Dec 14, p 1535) on the paper by Dr Akhras and Dr Jackson (Oct 26, p 1036) needs further clarification. Dr Singer and colleagues make a valid comment on the probable absence of efficacy of 20 mg nifedipine tablet at an average time of 7-4h after dose intake (no range given). Jackson and Akhras respond that they had established the efficacy of 20 mg nifedipine 10-12 h after dosage. The paper referred to1 is a double-blind comparison of isosorbide-5-mononitrate (5-ISMN) sustained release 40 mg given once daily, 5-ISMN plain tablets 20 mg given every 12 h, and 20 mg nifedipine "retard" given every 12 h (no brand name given), with a single-blind run-in placebo period. The study also contained a single-blind "run-out" placebo period after all active periods, but no data are provided for that. The study design is not satisfactory in terms of determining efficacy compared with placebo, and the only valid conclusion that might be drawn from that study is that the three treatments were equally effective. There is, however, reasonable doubt about that. Akhras and Jackson refer to two more studies of theirs when describing 5-ISMN as "effective, well-tolerated, antianginal agent with proven efficacy as monotherapy". 2,3 An open dose-titration study2 violates accepted principles of a proper angina study, and is the only study I have found that purports to show that the plain 20 mg 5-ISMN tablet every 24 h and 20 mg given every 12 h are effective 24hand 12 h after dosage, respectively. The other study3 is an interim report of the one published in The Lancet. Akhras and Jackson ignore dozens of well-controlled studies with proper double-blind placebo periods and with varying dosages from 20 mg twice daily (symmetrical or asymmetrical) to 40 mg twice daily and with sustained-release formulations 40 to 100 mg once daily.
My review of publications up to mid-19914 reveals that no adequately extended double-blind study on plain 5-ISMN tablets at a dose of 20 mg given every 12 h for more than a week shows a duration of efficacy of longer than 4 h, as measured by upright exercise in angina patients, even though attempts to show longer duration were made in several studies. One study on 20 mg 5-1 SMN in plain tablets given at 0800 and 1500 h shows efficacy 7 h after the morning dose and 5 h after the afternoon dose. For sustained-release preparations, no adequate study exists showing a duration of efficacy of 24 h; the longest is 12 h. Department of Medicine, Ostra Hospital, S-416 85 Goteborg, Sweden
GUNNAR F. NYBERG
F, Chambers J, Jefferies S, Jackson G. A randomised double-blind crossover study of isosorbide mononitrate and nifedipine retard in chronic stable angina. Int J Cardiol 1989; 24: 191-96. 2. Akhras F, Jeffenes S, Jackson G. Isosorbide-5-mononitrate effective monotherapy in chronic stable angina Z Kardiol 1985; 74 (suppl): 16-20. 3 Akhras F, Chambers J, Jackson G. An interim report on the efficacy of isosorbide-51. Akhras
mononitrate
in
a
sustained release formulation
in
patients with stable angina. In:
Julian DG, Rittinghausen R, Überbacher H, eds. Mononitrate II. Berlin:
Springer-Verlag, 1987:
184-87
4. Nyberg G. Current status of isosorbide-5-mononitrate therapy. In: Alpert JS, Rezakovic D, eds. Nitrate therapy and nitrate tolerance: current concepts and controversies. Berlin: Spnnger-Verlag (in press). 5. Thadani U & IS-5MN Study Group. Isosorbide-5-mononitrate (IS-5-MN) in angina pectoris: efficacy of AM and PM doses, lack of tolerance and zero hour effect during eccentric BID therapy. Circulation 1991; 83: II-730 (abstr 2903).
Nitrous oxide
as
neurotransmitter
SiR,—Dr Sanders in his conference report on nitric oxide (NO) (Jan 4, p 50) remarks on the recent discovery that this gas is involved in neurotransmission. The discovery that gases are involved in neurotransmission is older than this. The idea that another oxide of nitrogen (nitrous oxide, NO) could be directly involved in neurotransmission appeared in 1980.1 Substantive evidence from radioreceptor binding followed in 1983,2 this being confirmed at the US National Institutes of Health in 1989.3 Both laboratories found evidence that the endogenous gas oxygen might also be involved in neurotransmission. 1,3 The finding that both NO and N20 increase intracellular levels of cyclic GMP indicates that the resemblance between these two simple gaseous compounds may not rest on their identical elemental components alone.4 South African Brain Research Institute,
Waverley 2090, South Africa
MARK A. GILLMAN
1. Gillman MA, Kok L, Lichtigfeld FJ. Paradoxical effect of naloxone on nitrous oxide
analgesia in man Eur J Pharmacol 1980; 61: 175-77. 2 Daras C, Cantrill RC, Gillman MA. 3(H)-Naloxone displacement: evidence for nitrous oxide as opioid receptor agonist Eur J Pharmacol 1983; 89: 177-78. 3. On C, Ford-Rice F, Landon ED. Effects of nitrous oxide and halothane on mu and kappa opioid receptors in guinea-pig brain. Anesthesiology 1989, 70: 541-44. 4. Gillman MA. The role of gases in neurotransmission. S Afr J Sci 1991; 87: 573.
Six pregnancies following donation of both oocytes and sperm SIR,-An article in the Sunday Times of Dec 15, 199 1, headlined "Off-the-shelf babies’ breakthrough?" heralded the use of excess cryopreserved embryos from fertile couples being used by infertile couples who will have made no genetic contribution to the embryos generated. For a child to be bom to a couple who have made no genetic contribution from their own gametes is not new. We achieved pregnancies following the inception of an oocyte donor programme in 1986 when, in some circumstances, donor sperm was used because of a concurrent sperm problem. The first successful birth (not previously reported) was in August, 1987, to a 47-year-old woman whose 48-year-old husband had a serious sperm problem. Since then, four other births have occurred and one pregnancy is still in progress (table). All patients were treated after ethics committee approval. Some of our assisted conception patients have indicated that they wish to donate excess embryos for the benefit of others because they have completed their families by successful assisted conception. Our ethics committee has approved an embryo donation programme, which is now in operation.
308
25 mg and 2 x 100 mg cyclosporin. He had received numerous blood transfusions during 2 years for refractory anaemia which led to excessive iron overload, with serum ferritin of 6000 u.g/1 (normal 30-233). Iron overload due to haemochromatosis or multiple blood transfusions is a known risk factor for generalised infections with certain micro-organisms usually seen in simple colonisation or for infections such as Mucor spp and Yersinia enterocolitica.3Clearly, our patient had depressed cellular immunity caused by his lymphoproliferative disorder and drug treatment. However, he had had no other opportunistic infection. The well-known influence of iron on the growth rate of fastidious bacteria led us to consider iron overload as an important individual risk factor for such infection. C canimorsus should therefore be added to the list of micro-organisms that can produce bacteraemia in patients with chronic iron overload. Moreover, the value of simple blood culture techniques in the diagnosis of unusual bacterial infections should be emphasised.
PREGNANCIES WITH DONATED OOCYTES AND SPERM
*PR=poor responder, PM=perimenopausal, POF=premature tV = vaginal delivery, CS = caesarean section
ovarian
methylprednisolone
failure.
Hannover Medical School, D-3000 Hannover 61, Germany
A wider availability of oocyte donation is to be commended as an alternative to adoption, which is not realistic for most couples. The major impediment is the limited number of oocyte donors who come forward. Some fertility centres use oocytes/embryos from infertile couples which are in excess of the maximum number (three) now allowed for transfer for donation to other infertile couples, but this is questionable because 70% of couples, when asked, wish for embryos to be cryopreserved for their own potential use.’ We have similar concerns about using excess embryos from infertile couples for research; we think these should be generated for this purpose from fertile couples who have no need to achieve a further pregnancy and who have agreed to donate gametes for this specific end. Although the concept of creating life by using donated oocytes and sperm, or donated embryos, for unrelated recipients may be repugnant to some people we see it as an integral part of fertility management, provided that donors and recipients have been fully counselled. IAN CRAFT ELLY FINCHAM TALHA AL-SHAWAF
London Fertility and Gynaecology Centre, London W1 N 1AF, UK
1. Fincham E, Brinsden P, Craft I. Patient’s response to a questionnaire reproduction treatment. Ethical Prob Reprod Med 1989; 1: 25-27.
Departments of Medical Microbiology and Transfusion Medicine,
on
assisted
Opportunistic Capnocytophaga canimorsus infection SiR,—Although uncommon, systemic infections with the gramnegative bacterium Capnocytophaga canimorsus, formerly DF-2, have lately received particular attention, mainly because they may represent a serious complication of animal bites.1 We report a patient with capnocytophaga bacteraemia in unusual circumstances. A 36-year-old man who had no contact with domestic animals and seen regularly at this hospital for treatment of a T-gammalymphoproliferative disorder and refractory anaemia was admitted for fever and an erysipelas-like rash on his right calf. He was given 3 x 10 million units of penicillin G daily for 10 days. Blood cultures taken before treatment yielded a fastidious gram-negative bacterium subsequently identified as C canimorsus by its characteristic colony morphology and biochemical features.2 Three days after discharge, he again presented with fever, and capnocytophaga was isolated from all three new blood culture sets. Treatment with penicillin G was reinstituted, with the addition of tobramycin (3 x 100 mg daily) for four weeks. The sensitivity of the micro-organism had been established by minimum inhibitory concentration broth dilution assay. Under this combined treatment, the patient became rapidly afebrile and has remained so. Our patient was receiving immunosuppressive treatment for his lymphoproliferative disorder, with daily doses of
MICHEL PLETSCHETTE JÖRG KÖHL J. KUIPERS R. E. SCHMIDT
1. Zumla A,
Lipscombe G, Corbett M, McCarthy M. Dysgonic-fermenter type 2: an emerging zoonosis; report of two cases and review. Q JMed 1988; 68: 741-52. 2. Brenner DJ, Hollis DG, Fanning GR, Weaver RE. Capnocytophaga canimorsus sp nov (formerly CDD Group DF-2), a cause of septicaemia following dog-bite, and Capnocytophaga cynodegmi sp nov, a cause of localised wound infection following dog-bite. J Clin Microbiol 1989; 27: 231-35. 3. Bullen JJ, Ward CG, Rogers HJ. The critical role of iron in some clinical infections. Eur J Clin Microbiol Infect Dis 1991; 10: 613-17.
Hypercalcaemia due to all-trans retinoic acid SiR,—All-MM retinoic acid (ATRA) was introduced for acute promyelocytic leukaemia (APL) in 1988 and has been remarkably successful.’,’ Warrell et aP recorded 9 complete remissions in 11 patients. The reported side-effects of systemic ATRA treatment include headache, rash, nasal congestion, hypertriglyceridaemia, bone pain, and hepatic toxicity .1-3Hypercalcaemia is a side-effect of vitamin A, but it has not been recorded during treatment with ATRA. Many of the reported cases had a history of concomitant vitamin D ingestion, and serum vitamin A and vitamin D concentrations were not measured. We report a patient with APL in whom hypercalcaemia developed during treatment with ATRA. A 19-year-old man was diagnosed as having APL in January, 1990. After complete remission on chemotherapy he had autologous bone-marrow transplantation in October, 1990. He relapsed in July, 1991, and was given cytarabine and daunorubicin to reduce the number of blasts. ATRA (Hoffinan-La Roche), 40 mg/m2, was then started on Aug 15,1991. Initial plasma calcium and phosphorous concentrations were normal. Sustained headache, dryness of the lips, and bone pain around knees and hips developed. Bone-marrow examination 28 days after ATRA was started showed a second complete remission with abnormal maturation of granulocytes. Repeated laboratory tests revealed increasing calcium concentrations with normal serum phosphorus (table). Serum parathyroid hormone (PTH) was low and 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were suppressed. Tubular resorption of phosphorus was 90% and fractional excretion of calcium was 1-86%. ATRA was discontinued on Oct 23, after 9 weeks of treatment. Repeated blood tests on Nov 6 revealed normal calcium, PTH, and vitamin D values. Vitamin A is known to cause hypercalcaemia.4 However, the mechanism for each vitamin A compound has not been clearly defined. Vitamin A stimulates secretion of PTH in bovine tissuess and bone parathyroid resorption in thyroparathyroidectomised rates 6 In our patient PTH was inhibited during hypercalcaemia and returned to normal after vitamin A was stopped, suggesting that increased bone resorption mainly accounted for hypercalcaemia due to ATRA. Vitamin D concentrations were normal, which does not accord with the possibility of concomitant intake of vitamin D and vitamin A.
function before such losses occur must be preferable, and this can be achieved only if an accurate and reproducible method of determining renal function is used to monitor patients with potentially progressive disease. To this end, clinicians have most 24 h creatinine clearance. This has been be inaccurate but also of poor repeatability with figures for reproducibility of 20% and 30% .’* Its role in monitoring function has to be seen as questionable. In contrast, plasma clearance measurements of filtration markers such as 51Cr-EDT A have a reproducibility of 3-5 %, probably the best that can be achieved, allowing for physiological variation.45 Such methods are rarely used for objective clinical monitoring because they are time-consuming, the availability of nuclear medicine skills is limited, and repeated injection of radiopharmaceuticals should be avoided. Into the area comes the non-ionic contrast medium iohexol, which, it is suggested, might be considered as an alternative to inulin clearance, widely regarded as the "gold standard". There are of course no "24 carat gold" standards for GFR. Iohexol has the same excretory properties as inulin but none of the handling problems of that rather insoluble and unstable polysaccharide; and it is not a radiopharmaceutical. At the low doses possible for clearance studies iohexol is free of the dose-related adverse effects attributable to contrast media. Assay has been made simple by the implementation of X-ray radiofluorescence analysis.’1 Since iohexol is an ordinary radiographic contrast, GFR measurement can accompany any intravascular contrast examination. We believe that the technique offers considerable potential for increased detection and objective monitoring of renal impairment and that it is an important advance.
commonly adopted the
shown not only to
Department of Urology, Stepping Hill Hospital,
Stockport SK2 7JE,UK
STEPHEN BROWN
1 Brown
SCW, O’Reilly PH. Iohexol clearance for the determination of glomerular filtration rate in clinical practice: evidence for a new gold standard. J Urol 1991; 146:
675-79. 2. Gabnel R. Time to scrap creatinine clearance? Br Med 1986; 293: 1119-20. J 3. Dodge WF, Travis LD, Daeschner CW. Comparison of endogenous creatinine clearance with inulin clearance. Am J Dis Child 1967; 113: 683-92 4. Brochner-Mortensen J, Rodbro P. Selection of routine method for determination of glomerular filtration rate in adult patients. Scand J Clin Lab Inv 1976; 36: 35-42. 5. Chantler C, Barratt TM. Estimation of glomerular filtration rate from plasma clearance of 51Cr-EDTA. Arch Dis Child 1972; 47: 613-17
Duration of efficacy of anti-anginal
drugs
SIR,-The discussion (Dec 14, p 1535) on the paper by Dr Akhras and Dr Jackson (Oct 26, p 1036) needs further clarification. Dr Singer and colleagues make a valid comment on the probable absence of efficacy of 20 mg nifedipine tablet at an average time of 7-4h after dose intake (no range given). Jackson and Akhras respond that they had established the efficacy of 20 mg nifedipine 10-12 h after dosage. The paper referred to1 is a double-blind comparison of isosorbide-5-mononitrate (5-ISMN) sustained release 40 mg given once daily, 5-ISMN plain tablets 20 mg given every 12 h, and 20 mg nifedipine "retard" given every 12 h (no brand name given), with a single-blind run-in placebo period. The study also contained a single-blind "run-out" placebo period after all active periods, but no data are provided for that. The study design is not satisfactory in terms of determining efficacy compared with placebo, and the only valid conclusion that might be drawn from that study is that the three treatments were equally effective. There is, however, reasonable doubt about that. Akhras and Jackson refer to two more studies of theirs when describing 5-ISMN as "effective, well-tolerated, antianginal agent with proven efficacy as monotherapy". 2,3 An open dose-titration study2 violates accepted principles of a proper angina study, and is the only study I have found that purports to show that the plain 20 mg 5-ISMN tablet every 24 h and 20 mg given every 12 h are effective 24hand 12 h after dosage, respectively. The other study3 is an interim report of the one published in The Lancet. Akhras and Jackson ignore dozens of well-controlled studies with proper double-blind placebo periods and with varying dosages from 20 mg twice daily (symmetrical or asymmetrical) to 40 mg twice daily and with sustained-release formulations 40 to 100 mg once daily.
My review of publications up to mid-19914 reveals that no adequately extended double-blind study on plain 5-ISMN tablets at a dose of 20 mg given every 12 h for more than a week shows a duration of efficacy of longer than 4 h, as measured by upright exercise in angina patients, even though attempts to show longer duration were made in several studies. One study on 20 mg 5-1 SMN in plain tablets given at 0800 and 1500 h shows efficacy 7 h after the morning dose and 5 h after the afternoon dose. For sustained-release preparations, no adequate study exists showing a duration of efficacy of 24 h; the longest is 12 h. Department of Medicine, Ostra Hospital, S-416 85 Goteborg, Sweden
GUNNAR F. NYBERG
F, Chambers J, Jefferies S, Jackson G. A randomised double-blind crossover study of isosorbide mononitrate and nifedipine retard in chronic stable angina. Int J Cardiol 1989; 24: 191-96. 2. Akhras F, Jeffenes S, Jackson G. Isosorbide-5-mononitrate effective monotherapy in chronic stable angina Z Kardiol 1985; 74 (suppl): 16-20. 3 Akhras F, Chambers J, Jackson G. An interim report on the efficacy of isosorbide-51. Akhras
mononitrate
in
a
sustained release formulation
in
patients with stable angina. In:
Julian DG, Rittinghausen R, Überbacher H, eds. Mononitrate II. Berlin:
Springer-Verlag, 1987:
184-87
4. Nyberg G. Current status of isosorbide-5-mononitrate therapy. In: Alpert JS, Rezakovic D, eds. Nitrate therapy and nitrate tolerance: current concepts and controversies. Berlin: Spnnger-Verlag (in press). 5. Thadani U & IS-5MN Study Group. Isosorbide-5-mononitrate (IS-5-MN) in angina pectoris: efficacy of AM and PM doses, lack of tolerance and zero hour effect during eccentric BID therapy. Circulation 1991; 83: II-730 (abstr 2903).
Nitrous oxide
as
neurotransmitter
SiR,—Dr Sanders in his conference report on nitric oxide (NO) (Jan 4, p 50) remarks on the recent discovery that this gas is involved in neurotransmission. The discovery that gases are involved in neurotransmission is older than this. The idea that another oxide of nitrogen (nitrous oxide, NO) could be directly involved in neurotransmission appeared in 1980.1 Substantive evidence from radioreceptor binding followed in 1983,2 this being confirmed at the US National Institutes of Health in 1989.3 Both laboratories found evidence that the endogenous gas oxygen might also be involved in neurotransmission. 1,3 The finding that both NO and N20 increase intracellular levels of cyclic GMP indicates that the resemblance between these two simple gaseous compounds may not rest on their identical elemental components alone.4 South African Brain Research Institute,
Waverley 2090, South Africa
MARK A. GILLMAN
1. Gillman MA, Kok L, Lichtigfeld FJ. Paradoxical effect of naloxone on nitrous oxide
analgesia in man Eur J Pharmacol 1980; 61: 175-77. 2 Daras C, Cantrill RC, Gillman MA. 3(H)-Naloxone displacement: evidence for nitrous oxide as opioid receptor agonist Eur J Pharmacol 1983; 89: 177-78. 3. On C, Ford-Rice F, Landon ED. Effects of nitrous oxide and halothane on mu and kappa opioid receptors in guinea-pig brain. Anesthesiology 1989, 70: 541-44. 4. Gillman MA. The role of gases in neurotransmission. S Afr J Sci 1991; 87: 573.
Six pregnancies following donation of both oocytes and sperm SIR,-An article in the Sunday Times of Dec 15, 199 1, headlined "Off-the-shelf babies’ breakthrough?" heralded the use of excess cryopreserved embryos from fertile couples being used by infertile couples who will have made no genetic contribution to the embryos generated. For a child to be bom to a couple who have made no genetic contribution from their own gametes is not new. We achieved pregnancies following the inception of an oocyte donor programme in 1986 when, in some circumstances, donor sperm was used because of a concurrent sperm problem. The first successful birth (not previously reported) was in August, 1987, to a 47-year-old woman whose 48-year-old husband had a serious sperm problem. Since then, four other births have occurred and one pregnancy is still in progress (table). All patients were treated after ethics committee approval. Some of our assisted conception patients have indicated that they wish to donate excess embryos for the benefit of others because they have completed their families by successful assisted conception. Our ethics committee has approved an embryo donation programme, which is now in operation.
308
25 mg and 2 x 100 mg cyclosporin. He had received numerous blood transfusions during 2 years for refractory anaemia which led to excessive iron overload, with serum ferritin of 6000 u.g/1 (normal 30-233). Iron overload due to haemochromatosis or multiple blood transfusions is a known risk factor for generalised infections with certain micro-organisms usually seen in simple colonisation or for infections such as Mucor spp and Yersinia enterocolitica.3Clearly, our patient had depressed cellular immunity caused by his lymphoproliferative disorder and drug treatment. However, he had had no other opportunistic infection. The well-known influence of iron on the growth rate of fastidious bacteria led us to consider iron overload as an important individual risk factor for such infection. C canimorsus should therefore be added to the list of micro-organisms that can produce bacteraemia in patients with chronic iron overload. Moreover, the value of simple blood culture techniques in the diagnosis of unusual bacterial infections should be emphasised.
PREGNANCIES WITH DONATED OOCYTES AND SPERM
*PR=poor responder, PM=perimenopausal, POF=premature tV = vaginal delivery, CS = caesarean section
ovarian
methylprednisolone
failure.
Hannover Medical School, D-3000 Hannover 61, Germany
A wider availability of oocyte donation is to be commended as an alternative to adoption, which is not realistic for most couples. The major impediment is the limited number of oocyte donors who come forward. Some fertility centres use oocytes/embryos from infertile couples which are in excess of the maximum number (three) now allowed for transfer for donation to other infertile couples, but this is questionable because 70% of couples, when asked, wish for embryos to be cryopreserved for their own potential use.’ We have similar concerns about using excess embryos from infertile couples for research; we think these should be generated for this purpose from fertile couples who have no need to achieve a further pregnancy and who have agreed to donate gametes for this specific end. Although the concept of creating life by using donated oocytes and sperm, or donated embryos, for unrelated recipients may be repugnant to some people we see it as an integral part of fertility management, provided that donors and recipients have been fully counselled. IAN CRAFT ELLY FINCHAM TALHA AL-SHAWAF
London Fertility and Gynaecology Centre, London W1 N 1AF, UK
1. Fincham E, Brinsden P, Craft I. Patient’s response to a questionnaire reproduction treatment. Ethical Prob Reprod Med 1989; 1: 25-27.
Departments of Medical Microbiology and Transfusion Medicine,
on
assisted
Opportunistic Capnocytophaga canimorsus infection SiR,—Although uncommon, systemic infections with the gramnegative bacterium Capnocytophaga canimorsus, formerly DF-2, have lately received particular attention, mainly because they may represent a serious complication of animal bites.1 We report a patient with capnocytophaga bacteraemia in unusual circumstances. A 36-year-old man who had no contact with domestic animals and seen regularly at this hospital for treatment of a T-gammalymphoproliferative disorder and refractory anaemia was admitted for fever and an erysipelas-like rash on his right calf. He was given 3 x 10 million units of penicillin G daily for 10 days. Blood cultures taken before treatment yielded a fastidious gram-negative bacterium subsequently identified as C canimorsus by its characteristic colony morphology and biochemical features.2 Three days after discharge, he again presented with fever, and capnocytophaga was isolated from all three new blood culture sets. Treatment with penicillin G was reinstituted, with the addition of tobramycin (3 x 100 mg daily) for four weeks. The sensitivity of the micro-organism had been established by minimum inhibitory concentration broth dilution assay. Under this combined treatment, the patient became rapidly afebrile and has remained so. Our patient was receiving immunosuppressive treatment for his lymphoproliferative disorder, with daily doses of
MICHEL PLETSCHETTE JÖRG KÖHL J. KUIPERS R. E. SCHMIDT
1. Zumla A,
Lipscombe G, Corbett M, McCarthy M. Dysgonic-fermenter type 2: an emerging zoonosis; report of two cases and review. Q JMed 1988; 68: 741-52. 2. Brenner DJ, Hollis DG, Fanning GR, Weaver RE. Capnocytophaga canimorsus sp nov (formerly CDD Group DF-2), a cause of septicaemia following dog-bite, and Capnocytophaga cynodegmi sp nov, a cause of localised wound infection following dog-bite. J Clin Microbiol 1989; 27: 231-35. 3. Bullen JJ, Ward CG, Rogers HJ. The critical role of iron in some clinical infections. Eur J Clin Microbiol Infect Dis 1991; 10: 613-17.
Hypercalcaemia due to all-trans retinoic acid SiR,—All-MM retinoic acid (ATRA) was introduced for acute promyelocytic leukaemia (APL) in 1988 and has been remarkably successful.’,’ Warrell et aP recorded 9 complete remissions in 11 patients. The reported side-effects of systemic ATRA treatment include headache, rash, nasal congestion, hypertriglyceridaemia, bone pain, and hepatic toxicity .1-3Hypercalcaemia is a side-effect of vitamin A, but it has not been recorded during treatment with ATRA. Many of the reported cases had a history of concomitant vitamin D ingestion, and serum vitamin A and vitamin D concentrations were not measured. We report a patient with APL in whom hypercalcaemia developed during treatment with ATRA. A 19-year-old man was diagnosed as having APL in January, 1990. After complete remission on chemotherapy he had autologous bone-marrow transplantation in October, 1990. He relapsed in July, 1991, and was given cytarabine and daunorubicin to reduce the number of blasts. ATRA (Hoffinan-La Roche), 40 mg/m2, was then started on Aug 15,1991. Initial plasma calcium and phosphorous concentrations were normal. Sustained headache, dryness of the lips, and bone pain around knees and hips developed. Bone-marrow examination 28 days after ATRA was started showed a second complete remission with abnormal maturation of granulocytes. Repeated laboratory tests revealed increasing calcium concentrations with normal serum phosphorus (table). Serum parathyroid hormone (PTH) was low and 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were suppressed. Tubular resorption of phosphorus was 90% and fractional excretion of calcium was 1-86%. ATRA was discontinued on Oct 23, after 9 weeks of treatment. Repeated blood tests on Nov 6 revealed normal calcium, PTH, and vitamin D values. Vitamin A is known to cause hypercalcaemia.4 However, the mechanism for each vitamin A compound has not been clearly defined. Vitamin A stimulates secretion of PTH in bovine tissuess and bone parathyroid resorption in thyroparathyroidectomised rates 6 In our patient PTH was inhibited during hypercalcaemia and returned to normal after vitamin A was stopped, suggesting that increased bone resorption mainly accounted for hypercalcaemia due to ATRA. Vitamin D concentrations were normal, which does not accord with the possibility of concomitant intake of vitamin D and vitamin A.
