- Email: [email protected]
HLA-TYPES IN PORPHYRIA CUTANEA TARDA
155 microbial results with variations in the RIDA when
Mollin’s work.10
they
refer
HLA-ANTIGEN
to
FREQUENCIES
IN PORPHYRIA CUTANEA TARDA
The controversy of protozoan B12assays versus alternate methods bring to mind the following. The history of a biochemical analytical method falls into three
phases.
Phase I. -A simple, accurate method is proposed and accepted (e.g., Euglena and 0. malhamensis assays for B, ). Phase 2.-Modifications and improvements galore are introduced (e.g., RIDA), obscuring simplicity without commensurate gain in accuracy and often obfuscating results by not being specific enough for that which is being
analysed. Phase3.-A new generation of
simplicity. These protozoal methods exemplify this sequence. The twenty years of reliable data 3,4,6-11should dissolve England and Linnell’s objections: they need but to consult their own references (e.g.,
Chanarin8 and Mollin7,10). The reluctance of clinicians to use protozoal assays, especially that with O. malhamensis (whose cobalamin specificity entirely parallels that of birds and mammals),may be attributable to conservatism. For example, a prominent American author12 does not recommend protozoal assays because they have not been much used; not being recommended, they are not much used, a self-fulfilling injunction made in the absence of actual experience. Perhaps such an injunction may have confused the thinking of England and Linnell when they wrote their occasional survey. Departments Preventive Medicine and Medicine, New Jersey Medical School, East Orange, New Jersey 07018, U.S.A.
HERMAN BAKER OSCAR FRANK
Department of Biology,
Pace University, New York
*n 50 for PCT, 600 for controls I, and 2146 (A3, AW24) or 2117 (B7, controls II. RR relative risk. =
analysts rediscovers the validity of the original
B 14) for
quencies of HLA A3, AW24 and B7 were found in the PCT patients (see table). The increases for A3 and B7 remain significant when p values are corrected for the number of antigens tested and when a larger middle European control populations is used for comparisons. These findings in PCT, a disease based on metabolic defects of iron and porphyrins support the hypothesis that genes controlling iron metabolism
are
linked
to
the HLA system.
Tissue Typing Laboratory, Institute for Blood Coagulation and Transfusion Medicine,
Dermatology Clinic, University of Düsseldorf, 4000 Düsseldorf1, West Germany
B. M. E. KUNTZ G. GOERZ
Biotest Serum Institute, Frankfurt/Main
H. H. SONNEBORN R. LISSNER
SEYMOUR H. HUTNER PRE-FILLED ADRENALINE SYRINGES
HLA-TYPES IN PORPHYRIA CUTANEA TARDA
SIR,—Bregman et al.reported an iron-overload associated myopathy in haemodialysis patients which correlated with the presence of the HLA-antigens A3, B7, and B14, antigens well known to be associated with idiopathic haemochromatosis. Porphyria cutanea tarda (PCT) is characterised by an overproduction of uroporphyrin in the liver and hepatic iron overload. A partial deficiency of the enzyme uroporphyrinogen decarboxylase in the liver and red cells of PCT patients has been reported by Elderzand Felsher.3 Like haemochromatosis PCT responds to therapeutic bleedings (i.e., removal of iron).4The underlying aberration of iron metabolism is not clearly understood, however. Exogenous factors, besides iron overload, are required for disease manifestation, such as exposure to chemicals or drugs (e.g., hexachlorobenzene,5and inducers of the cytochrome P-450 system). Tissue typingfor thirty antigens of the HLA A and B loci was done on 50 PCT patients (29 male, 21 female). The diagnosis was based on a typical clinical picture of blisters, hyperpigmentation, and hypertrichosis of exposed skin and on the increased excretion of uroporphyrins and heptaporphyrins in the urine /Increased freDL, Huffbrand AV, Ward PG, Lewis SM. Interlaboratory comparison of B1 2 assay J Clin Pathol 1980; 33: 243-48. 11. Baker H, Frank O, Hutner SH. Vitamin analysis in medicine. In. Goodhart RS, Shils ME, eds. Modern nutrition in health and disease. New York: Lea and Febiger, 1980:
SIR,—We read with interest Dr Ackroyd’s comments (Nov. 29, p. 1190) concerning the availability of pre-filled syringes containing adrenaline for the emergency treatment of anaphylaxis. We would also endorse the advantages of pre-filled syringes over traditional ampoules in an emergency. International Medication Systems (U.K.) Ltd has been marketing three presentations of adrenaline hydrochloride solution in prefilled syringes in the U. K. for four years. These are 1:10 000 (1mg in 10 ml) with both a 21 gauge 1112 in and an 18 gauge 31/2 in intracardiac needle. The third is a paediatric formulation of0’33 mg in 3 ml with 22 gauge 11/2 in needle. All are prescribable under the N.H.S. and are available to general practitioners and hospital consultants. In the United States further presentations of adrenaline are marketed to fill the need commented on by Dr Ackroyd. A’single dose pre-filled syringe containing 1: 1000 adrenaline with a 25 gauge 5/s in needle allows easy administration in cases of emergency acute This will shortly be available in the U.K. and anyone interested in this product should contact us.
anaphylaxis.
International Medication
Systems (U.K) Ltd, Daventry, Northamptonshire NN 11 5PJ
DIABETES AND ECT
10. Mollin
serum vitamin
611-40. 12. Sauberlich H. Vitamins. In: Sauberlich H, Dowdy RP, Skala JH, eds. Laboratory tests for the assessment of nutritional status Cleveland. CRC Press, 1974: 4-92 1 Bregman H, Gelfand MC, Winchester FJ, Manz HJ, Knepshield JH, Schreiner GE
Iron-overload associated
2
myopathy in patients on maintenance haemodialysis: a histocompatibility-linked disorder. Lancet 1980, n: 882-85 Elder GH, Path MRC, Lee GB, Tovey JA Decreased activity of hepatic uroporphynnogen decarboxylase in sporadic porphyria cutanea tarda N Engl J Med 1978; 299: 274-78 BF, Norris ME, Shith JC Red cell uroporphyrinogen decarboxylase in porphyria N Engl J Med 1978; 299: 1095-98 Ippen H. Die spate Hautporphyrie (porphyria cutanea tarda) und ihre Behandlungsm&oacgr;glichkeiten Deutsche Med Wschr 1961; 86: 127 Ockner RK, Schmid R Acquired porphyria in man and rat due to hexachlorobenzene intoxication Nature 1961, 189: 499-501. Terasaki PI, McClelland JD Microdroplet assay of human serum cytotoxins Nature 1964, 204: 998-1000 Doss M Analytical and preparative thin layer chromatography of porphyrinmethylesters Z Klin Chem Klin Biochem 1970, 8: 197-203
3 Felsher 4
5 6 7
ROSEMARY WRIGHT
SIR,-Dr Pyke and Dr Watkins (Nov. 1, p. 980) claim that our results (Oct. 11, p. 775) were inconclusive. However, their claim that our results could have been achieved by simple dietary measures is not valid. The drop in blood sugar was seen 3 days after ECT and was consistent in all our cases (except no. 3, where consistently lowered blood sugars were produced 2 weeks later). The patients were on a free diet after ECT and their weight was returning to their prediabetes level, as explained in the two pilot cases. The effect was seen in diabetics of recent onset, not in old diabetics. Department of Medicine, College of Medicine, University of Baghdad, Baghdad, Iraq 8 Baur
OMAR FAKHRI ADNAN FADHLI RAFI EL RAWI
MP, Danilovs JA Population analysis of HLA-A,B,C,DR and other Antigens (in press)
markers Tissue
genetic
Mollin’s work.10
they
refer
HLA-ANTIGEN
to
FREQUENCIES
IN PORPHYRIA CUTANEA TARDA
The controversy of protozoan B12assays versus alternate methods bring to mind the following. The history of a biochemical analytical method falls into three
phases.
Phase I. -A simple, accurate method is proposed and accepted (e.g., Euglena and 0. malhamensis assays for B, ). Phase 2.-Modifications and improvements galore are introduced (e.g., RIDA), obscuring simplicity without commensurate gain in accuracy and often obfuscating results by not being specific enough for that which is being
analysed. Phase3.-A new generation of
simplicity. These protozoal methods exemplify this sequence. The twenty years of reliable data 3,4,6-11should dissolve England and Linnell’s objections: they need but to consult their own references (e.g.,
Chanarin8 and Mollin7,10). The reluctance of clinicians to use protozoal assays, especially that with O. malhamensis (whose cobalamin specificity entirely parallels that of birds and mammals),may be attributable to conservatism. For example, a prominent American author12 does not recommend protozoal assays because they have not been much used; not being recommended, they are not much used, a self-fulfilling injunction made in the absence of actual experience. Perhaps such an injunction may have confused the thinking of England and Linnell when they wrote their occasional survey. Departments Preventive Medicine and Medicine, New Jersey Medical School, East Orange, New Jersey 07018, U.S.A.
HERMAN BAKER OSCAR FRANK
Department of Biology,
Pace University, New York
*n 50 for PCT, 600 for controls I, and 2146 (A3, AW24) or 2117 (B7, controls II. RR relative risk. =
analysts rediscovers the validity of the original
B 14) for
quencies of HLA A3, AW24 and B7 were found in the PCT patients (see table). The increases for A3 and B7 remain significant when p values are corrected for the number of antigens tested and when a larger middle European control populations is used for comparisons. These findings in PCT, a disease based on metabolic defects of iron and porphyrins support the hypothesis that genes controlling iron metabolism
are
linked
to
the HLA system.
Tissue Typing Laboratory, Institute for Blood Coagulation and Transfusion Medicine,
Dermatology Clinic, University of Düsseldorf, 4000 Düsseldorf1, West Germany
B. M. E. KUNTZ G. GOERZ
Biotest Serum Institute, Frankfurt/Main
H. H. SONNEBORN R. LISSNER
SEYMOUR H. HUTNER PRE-FILLED ADRENALINE SYRINGES
HLA-TYPES IN PORPHYRIA CUTANEA TARDA
SIR,—Bregman et al.reported an iron-overload associated myopathy in haemodialysis patients which correlated with the presence of the HLA-antigens A3, B7, and B14, antigens well known to be associated with idiopathic haemochromatosis. Porphyria cutanea tarda (PCT) is characterised by an overproduction of uroporphyrin in the liver and hepatic iron overload. A partial deficiency of the enzyme uroporphyrinogen decarboxylase in the liver and red cells of PCT patients has been reported by Elderzand Felsher.3 Like haemochromatosis PCT responds to therapeutic bleedings (i.e., removal of iron).4The underlying aberration of iron metabolism is not clearly understood, however. Exogenous factors, besides iron overload, are required for disease manifestation, such as exposure to chemicals or drugs (e.g., hexachlorobenzene,5and inducers of the cytochrome P-450 system). Tissue typingfor thirty antigens of the HLA A and B loci was done on 50 PCT patients (29 male, 21 female). The diagnosis was based on a typical clinical picture of blisters, hyperpigmentation, and hypertrichosis of exposed skin and on the increased excretion of uroporphyrins and heptaporphyrins in the urine /Increased freDL, Huffbrand AV, Ward PG, Lewis SM. Interlaboratory comparison of B1 2 assay J Clin Pathol 1980; 33: 243-48. 11. Baker H, Frank O, Hutner SH. Vitamin analysis in medicine. In. Goodhart RS, Shils ME, eds. Modern nutrition in health and disease. New York: Lea and Febiger, 1980:
SIR,—We read with interest Dr Ackroyd’s comments (Nov. 29, p. 1190) concerning the availability of pre-filled syringes containing adrenaline for the emergency treatment of anaphylaxis. We would also endorse the advantages of pre-filled syringes over traditional ampoules in an emergency. International Medication Systems (U.K.) Ltd has been marketing three presentations of adrenaline hydrochloride solution in prefilled syringes in the U. K. for four years. These are 1:10 000 (1mg in 10 ml) with both a 21 gauge 1112 in and an 18 gauge 31/2 in intracardiac needle. The third is a paediatric formulation of0’33 mg in 3 ml with 22 gauge 11/2 in needle. All are prescribable under the N.H.S. and are available to general practitioners and hospital consultants. In the United States further presentations of adrenaline are marketed to fill the need commented on by Dr Ackroyd. A’single dose pre-filled syringe containing 1: 1000 adrenaline with a 25 gauge 5/s in needle allows easy administration in cases of emergency acute This will shortly be available in the U.K. and anyone interested in this product should contact us.
anaphylaxis.
International Medication
Systems (U.K) Ltd, Daventry, Northamptonshire NN 11 5PJ
DIABETES AND ECT
10. Mollin
serum vitamin
611-40. 12. Sauberlich H. Vitamins. In: Sauberlich H, Dowdy RP, Skala JH, eds. Laboratory tests for the assessment of nutritional status Cleveland. CRC Press, 1974: 4-92 1 Bregman H, Gelfand MC, Winchester FJ, Manz HJ, Knepshield JH, Schreiner GE
Iron-overload associated
2
myopathy in patients on maintenance haemodialysis: a histocompatibility-linked disorder. Lancet 1980, n: 882-85 Elder GH, Path MRC, Lee GB, Tovey JA Decreased activity of hepatic uroporphynnogen decarboxylase in sporadic porphyria cutanea tarda N Engl J Med 1978; 299: 274-78 BF, Norris ME, Shith JC Red cell uroporphyrinogen decarboxylase in porphyria N Engl J Med 1978; 299: 1095-98 Ippen H. Die spate Hautporphyrie (porphyria cutanea tarda) und ihre Behandlungsm&oacgr;glichkeiten Deutsche Med Wschr 1961; 86: 127 Ockner RK, Schmid R Acquired porphyria in man and rat due to hexachlorobenzene intoxication Nature 1961, 189: 499-501. Terasaki PI, McClelland JD Microdroplet assay of human serum cytotoxins Nature 1964, 204: 998-1000 Doss M Analytical and preparative thin layer chromatography of porphyrinmethylesters Z Klin Chem Klin Biochem 1970, 8: 197-203
3 Felsher 4
5 6 7
ROSEMARY WRIGHT
SIR,-Dr Pyke and Dr Watkins (Nov. 1, p. 980) claim that our results (Oct. 11, p. 775) were inconclusive. However, their claim that our results could have been achieved by simple dietary measures is not valid. The drop in blood sugar was seen 3 days after ECT and was consistent in all our cases (except no. 3, where consistently lowered blood sugars were produced 2 weeks later). The patients were on a free diet after ECT and their weight was returning to their prediabetes level, as explained in the two pilot cases. The effect was seen in diabetics of recent onset, not in old diabetics. Department of Medicine, College of Medicine, University of Baghdad, Baghdad, Iraq 8 Baur
OMAR FAKHRI ADNAN FADHLI RAFI EL RAWI
MP, Danilovs JA Population analysis of HLA-A,B,C,DR and other Antigens (in press)
markers Tissue
genetic