1036 IS BLOOD CONTAINING ANTI-HBs INFECTIVE? SiR,—Transfusion of blood containing anti-HBs is still controversial. 1,2 There are some indications that anti-HBs could be an additional serological marker for the infective agent causing hepatitis B.3,44 In a prospective study of patients undergoing open-heart surgery4 we found a statistically significant correlation between the use of anti-HBs-positive blood units and post-transfusion HBsAgpositive or anti-HBs-positive hepatitis. Similar results have been presented by Mullis and Groband we think that 10-20% of anti-HBs-positive blood units are infective. Testing for anti-HBs and HBcAg may show which of those anti-HBs-positive blood units carry the infective agent. Unfortunately test systems for HBcAg and anti-HBc are not available for large-scale screening of blood donors. Because of our previous results4 we felt obliged to eliminate not only HBsAg-positive but also anti-HBs-positive blood units from transfusion in open-heart surgery. Thus far, the hepatitis-rate has fallen remarkably. In addition there are strong indications that in anti-HBs-positive blood donors liver diseases are found more often than expected in a healthy population. Our findings refer to open-heart surgery, which requires extracorporeal circulation and massive blood-transfusions, and we hesitate to recommend rejection of anti-HBs-positive blood units from transfusion in general. So, until a higher risk of hepatitis following transfusion of anti-HBs-positive blood units in other clinical situations has not been proved, the practical problems1 in rejecting anti-HBs-positive blood donors on a large scale do not exist.
and 11 mg. per 100 ml., respectively (alcohol dehydrogenase method), whereas chromatography (adsorbent ’Chromosorb’ 101) gave values of 34, 26, and 20 mg. per 100 ml. The latter method thus gave consistently higher results, and the presence of interfering substances was suspected. Screening of " ketone bodies " which could be derived from fat catabolism has so far revealed that isovaleraldehyde is isographic with ethyl alcohol on chromosorb 101, and diacetyl, valeraldehyde, and 3-pentanone coincident with alcohol on PEG 400. Falsely high readings for alcohol are therefore possible by gas chromato-
graphy. Necropsy of
a reputedly abstemious diabetic after a fatal car crash 1.,showed an apparent blood-alcohol level of 325 mg. per 100 ml. (ADH method 2) which is possibly explicable on the basis that acetoacetates and related compounds which had accumulated on cessation of respiration and bodily activity were converted to alcohol. Assuming a more severe hypoglycsemia in Mr Newson than the majority of passengers, such a mechanism could account for the higher alcohol content of his organs compared with the " controls " examined. The possibility of undiagnosed diabetes, or genetic disorders such as glycogen storage disease, hepatic, or pancreatic B-cell disease which could have similar effects, should not be excluded.
-
We thank Dr P.
Toseland, of Guy’s Hospital, for the blood
analyses. The Clinic, 46 St. Mary Street, High Wycombe, Bucks.
H. J. E. Cox L. F. RUTTER.
I. Medical
Clinic, University of Kiel, 12 Schittenhelmstrasse, 2300 Kiel, B.R.D.
HARALD LEHMANN MAX SCHLAAK.
MOORGATE TUBE DISASTER: DISPUTED ALCOHOL FINDINGS
SIR,-Failure of Dr Roy Goulding and Dr Ann Robinson agree on significance and levels of alcohol found in the postmortem examination of Driver Leslie Newson, and doubts concerning the possible origins of alcohol, prompt us to suggest reasons for the crash in the light of preliminary findings from a current investigation of endogenous
to
"
alcohol. Court evidence indicated that Mr Newson had been fasting for approximately 13 hours, and necropsy confirmed that the stomach was empty. In these circumstances and with due consideration of physical and mental activity between 4 A.M. when Mr Newson rose and the accident at 8.45 A.M., it is possible that glycogen stores were severely depleted or exhausted, and that a consequent hypoglycsemic episode occurred with attendant dizziness, mental confusion, and retarded reaction time. Hypoglyceemia may be regarded as transient diabetes, since it initiates breakdown of fat and protein to provide carbohydrates, which include the so-called " ketone bodies "-e.g., acetoacetates and related metabolites. These are readily convertible to alcohol by reversal of the acetaldeaccepted metabolic pathway-namely, alcohol hyde acetoacetates-particularly in acid conditions prevailing post mortem which favour the back reaction. In our investigation, 3 fasting abstinent mild diabetics (from whom medication had been withheld for 48 hours) were found to have apparent blood-alcohol levels of 26, 20, 1. 2. 3. 4. 5. 6.
Fiedler, H. Lancet, 1975, i, 341. Renton, P. M., Wadsworth, L. D. ibid. p. 528. Seifert, H., Ganzoni, A. ibid. 1974, ii, 1513. Schlaak, M., Lehmann, H., Schober, A. Digestion, 1974, 10, 380. Mullis, C. H., Grob, P. J. Schweiz. med. Wschr. 1974, 104, 1053. Boyes, B. E., Woolf, I. L., Jones, D. M., et al. Congreso mundial de Gastroenterologica, Mexico, 1974. Abstract no. 589.
GLUCAGON IN PATHOGENESIS OF DIABETES SiR,—Concerning the letter by Dr Vinik and Professor Jackson (March 22, p. 694), Professor Orci and I wish to acknowledge their pioneer work in demonstrating hyper-
glucagonsemia in patients with pancreatitis. While we are in general agreement with their comments, there are three points with which we disagree: (1) As will be demonstrated in the July, 1975, issue of journal of Clinical Investigation there is in extract of pig duodenum, as prepared by Dr Viktor Mutt, of Stockholm, a polypeptide which is immunometrically, physicochemically, and biologically indistinguishable from glucagon, having the same molecular weight, isoelectric point, and affinity for heterogenous antiglucagon antibodies and isolated rat-liver membranes as pancreatic glucagon. (2) A-cells, morphologically indistinguishable from pancreatic A-cells and taking specific immunofluorescent and immunoperoxidase stains, have been identified in the human stomach and duodenum.
(3) The authors misunderstood our reference to ketoacidosis as a bi-hormonal abnormality; hyperglucagonxmia will not cause ketosis unless there is severe insulin lack, which provides the extremely high quantities of free fatty acids necessary for marked ketone production. In other words, according to the McGarry, Wright, Foster proposal, the insulin lack causes hyperlipolysis and provides a surge of free fatty acids which can be converted to ketones only in the presence of glucagon. Dr Gerich will present at the Atlantic City meetings evidence that when glucagon is suppressed by somatostatin, insulin-deprived juvenile-type diabetics do not develop hyperketonxmia. Department of Internal Medicine, Southwestern Medical School, University of Texas, 5323 Harry Hines Boulevard, Dallas, Texas 75235, U.S.A. 1. 2.
ROGER H. UNGER.
Sunday Express, Jan. 20, 1974.
Spencer,
A. T. Personal communication.
Jan. 22, 1974.
i
and 11 mg. per 100 ml., respectively (alcohol dehydrogenase method), whereas chromatography (adsorbent ’Chromosorb’ 101) gave values of 34, 26, and 20 mg. per 100 ml. The latter method thus gave consistently higher results, and the presence of interfering substances was suspected. Screening of " ketone bodies " which could be derived from fat catabolism has so far revealed that isovaleraldehyde is isographic with ethyl alcohol on chromosorb 101, and diacetyl, valeraldehyde, and 3-pentanone coincident with alcohol on PEG 400. Falsely high readings for alcohol are therefore possible by gas chromato-
graphy. Necropsy of
a reputedly abstemious diabetic after a fatal car crash 1.,showed an apparent blood-alcohol level of 325 mg. per 100 ml. (ADH method 2) which is possibly explicable on the basis that acetoacetates and related compounds which had accumulated on cessation of respiration and bodily activity were converted to alcohol. Assuming a more severe hypoglycsemia in Mr Newson than the majority of passengers, such a mechanism could account for the higher alcohol content of his organs compared with the " controls " examined. The possibility of undiagnosed diabetes, or genetic disorders such as glycogen storage disease, hepatic, or pancreatic B-cell disease which could have similar effects, should not be excluded.
-
We thank Dr P.
Toseland, of Guy’s Hospital, for the blood
analyses. The Clinic, 46 St. Mary Street, High Wycombe, Bucks.
H. J. E. Cox L. F. RUTTER.
I. Medical
Clinic, University of Kiel, 12 Schittenhelmstrasse, 2300 Kiel, B.R.D.
HARALD LEHMANN MAX SCHLAAK.
MOORGATE TUBE DISASTER: DISPUTED ALCOHOL FINDINGS
SIR,-Failure of Dr Roy Goulding and Dr Ann Robinson agree on significance and levels of alcohol found in the postmortem examination of Driver Leslie Newson, and doubts concerning the possible origins of alcohol, prompt us to suggest reasons for the crash in the light of preliminary findings from a current investigation of endogenous
to
"
alcohol. Court evidence indicated that Mr Newson had been fasting for approximately 13 hours, and necropsy confirmed that the stomach was empty. In these circumstances and with due consideration of physical and mental activity between 4 A.M. when Mr Newson rose and the accident at 8.45 A.M., it is possible that glycogen stores were severely depleted or exhausted, and that a consequent hypoglycsemic episode occurred with attendant dizziness, mental confusion, and retarded reaction time. Hypoglyceemia may be regarded as transient diabetes, since it initiates breakdown of fat and protein to provide carbohydrates, which include the so-called " ketone bodies "-e.g., acetoacetates and related metabolites. These are readily convertible to alcohol by reversal of the acetaldeaccepted metabolic pathway-namely, alcohol hyde acetoacetates-particularly in acid conditions prevailing post mortem which favour the back reaction. In our investigation, 3 fasting abstinent mild diabetics (from whom medication had been withheld for 48 hours) were found to have apparent blood-alcohol levels of 26, 20, 1. 2. 3. 4. 5. 6.
Fiedler, H. Lancet, 1975, i, 341. Renton, P. M., Wadsworth, L. D. ibid. p. 528. Seifert, H., Ganzoni, A. ibid. 1974, ii, 1513. Schlaak, M., Lehmann, H., Schober, A. Digestion, 1974, 10, 380. Mullis, C. H., Grob, P. J. Schweiz. med. Wschr. 1974, 104, 1053. Boyes, B. E., Woolf, I. L., Jones, D. M., et al. Congreso mundial de Gastroenterologica, Mexico, 1974. Abstract no. 589.
GLUCAGON IN PATHOGENESIS OF DIABETES SiR,—Concerning the letter by Dr Vinik and Professor Jackson (March 22, p. 694), Professor Orci and I wish to acknowledge their pioneer work in demonstrating hyper-
glucagonsemia in patients with pancreatitis. While we are in general agreement with their comments, there are three points with which we disagree: (1) As will be demonstrated in the July, 1975, issue of journal of Clinical Investigation there is in extract of pig duodenum, as prepared by Dr Viktor Mutt, of Stockholm, a polypeptide which is immunometrically, physicochemically, and biologically indistinguishable from glucagon, having the same molecular weight, isoelectric point, and affinity for heterogenous antiglucagon antibodies and isolated rat-liver membranes as pancreatic glucagon. (2) A-cells, morphologically indistinguishable from pancreatic A-cells and taking specific immunofluorescent and immunoperoxidase stains, have been identified in the human stomach and duodenum.
(3) The authors misunderstood our reference to ketoacidosis as a bi-hormonal abnormality; hyperglucagonxmia will not cause ketosis unless there is severe insulin lack, which provides the extremely high quantities of free fatty acids necessary for marked ketone production. In other words, according to the McGarry, Wright, Foster proposal, the insulin lack causes hyperlipolysis and provides a surge of free fatty acids which can be converted to ketones only in the presence of glucagon. Dr Gerich will present at the Atlantic City meetings evidence that when glucagon is suppressed by somatostatin, insulin-deprived juvenile-type diabetics do not develop hyperketonxmia. Department of Internal Medicine, Southwestern Medical School, University of Texas, 5323 Harry Hines Boulevard, Dallas, Texas 75235, U.S.A. 1. 2.
ROGER H. UNGER.
Sunday Express, Jan. 20, 1974.
Spencer,
A. T. Personal communication.
Jan. 22, 1974.
i
