62
BLOOD PROTEIN CAND PROTEIN S MEASUREMENTS IN INFANT AND PARENTS
have led
to self-immunisation, accounting for the raised LPS antibody concentrations. Part of the benefit of severe physical training might therefore be
the induction of LPS antibodies which could reduce any endotoxaemia caused by physical heat stress, as you suggest. It remains to be seen whether the "doping" of an athlete with parenteral administration of anti-LPS IgG leads to his improved performance in a medium to long-distance race or in a soccer game on a warm day. If so, miners, pilots, soldiers, and possibly racehorses, might also benefit. -Normai
range (/m!)
in aamts snown m
parentneses
deficiency diagnosed. The thrombosis can be controlled by oral warfarin and cyroprecipitate transfusion every other day. daily To our knowledge this report is the first of homozygous PS deficiency associated with neonatal purpura fulminans. The treatment seems to be life-long replacement therapy, and fresh frozen plasma is planned to replace cryoprecipitate when the patient grows older. PS concentrate, the ideal treatment for this baby, is not yet available in Thailand. was
Department of Paediatrics, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado, USA
CHULARATANA MAHASANDANA VINAI SUVATTE RICHARD A. MARLAR MARILYN J. MANCO-JOHNSON LINDA J. JACOBSON WILLIAM E. HATHAWAY
HE, Katz J, Marble R, Griffin JH. Inherited protein C deficiency and coumarin responsive chronic relapsing purpura fulminans in a newborn infant. Lancet 1983; ii: 1165-68. 2. Seligsohn U, Berger A, Abend M, et al. Homozygous protein C deficiency manifested by massive venous thrombosis in the newborn. N Engl J Med 1984; 310: 559-62. 3. Marciniak E, Wilson HD, Marlar RA. Neonatal purpura fulminans: a genetic disorder related to the absence of protein C in blood. Blood 1985; 65: 15-20. 4. Yuen P, Cheung A, Lin HJ, et al. Purpura fulminans in a Chinese boy with congenital protein C deficiency. Pediatrics 1986; 77: 670-76. 5. Manco-Johnson MJ, Marlar RA, Jacobson LJ, Hays T, Warady BA. Severe protein C deficiency in newborn infants. J Pediatr 1988; 113: 359-63. 6. Marlar RA, Montgomery RR, Broekmans AW. Diagnosis and treatment of homozygous protein C deficiency. J Pediatr 1989; 114: 528-34. 7 Comp PC, Nixon RR, Cooper R, Esmon CT. Familial protein S deficiency is associated with recurrent thrombosis. J Clin Invest 1984; 74: 2082-88. 8. Comp PC, Doray D, Patton D, Esmon CT. An abnormal plasma distribution of protein S occurs in functional protein S deficiency. Blood 1986; 67: 504. 1. Branson
Endotoxins in heatstroke SIR,-Indirect evidence supports your suggestion (Nov 4, p 1137) that inducing high levels of antibodies to lipopolysaccharide (LPS) is beneficial in the treatment of heat stress. 81 % of competitors in an ultramarathon (89-5 km) who collapsed along the way or were carried to the medical tent at the finishing line, had raised plasma LPS concentrations (including two in the reported lethal range). They also had high indices of nausea/vomiting/diarrhoeasymptoms produced by LPS-and they needed hours to days to recover. The remaining 19% with LPS in the normal range had far fewer and less severe episodes of nausea, vomiting, and diarrhoea, and they recovered within minutes to an hour or two. Those with low concentrations of plasma LPS had high levels of "natural" LPS IgG antibodies and vice versa. In the group of runners who managed to finish the race before collapsing, those with the lowest LPS and highest anti-LPS IgG concentrations performed betterie, they finished sooner. Racehorses, too, showed rises in LPS at the end of a stakes race .2 In a triathlon, athletes who trained the hardest (most miles jogged, bicycled, or swum) during the two weeks before the contest had the highest levels of natural anti-LPS IgG at the start of the race and lowest LPS concentrations at the end.3 Prolonged severe exercise may lead to periods of hypoxia, intestinal ischaemia, and raised body temperature. Short periods of expeirmental hypoxia,4 intestinal ischaemia,s or body temperature of 41-42°C6 led to the entry of large quantities of LPS into the circulation. This LPS may
Department of Physiology, University of Natal Medical School, Durban, South Africa
STEPHEN L. GAFFIN
JG, Gaffin SL, Wells MT, et al. Endotoxaemia in exhausted runners following a long distance race. S Afr Med J 1988; 73: 533-36. 2. Baker B, Gaffin SL, Wells MT, Brock-Utne JG. Endotoxaemia in race horses following exertion. J S Afr Vet Assoc 1988; 59: 63-66. 3. Bosenberg AT, Brock-Utne JG, Wells MTB, et al. Strenuous exercise causes systematic endotoxaemia. J Appl Physiol 1988; 65: 106-08. 4. Gaffin SL, Brock-Utne JG, Zanotti A, Wells MTB. Hypoxia induced endotoxemia in primates. Aviat Space Environ Med 1986; 57: 1044-49. 5. Gathiram P, Wells MT, Raidoo D, et al. Changes in plasma lipopolysaccharide concentrations in portal venous and systemic arterial blood during intestinal ischemia in primates. Circ Shock 1989; 27: 103-09. 6. Gathiram P, Wells MT, Raidoo D, et al. Portal and systemic plasma lipopolysaccharide concentrations in heat-stressed primates. Circ Shock 1988; 25: 1. Brock-Utne
223-30.
Human insulin and
hypoglycaemia
SIR,-Dr Egger and Dr Teuscher (Nov 25, p 1268) report that the introduction of human insulin in the Canton of Berne, Switzerland, caused a huge increase in admissions for severe hypoglycaemia to eight public hospitals during 1984-87. They attributed these cases of hypoglycaemia to a reduced awareness of hypoglycaemia, which may be partly caused by differences in counterregulatory responses to human and porcine insulin.1 The rise in the number of admissions seems to correlate quite well with the introduction of human insulin, but may also have been caused by other factors such as lowering of the mean HbA, value in the Canton of Berne in the pursuit of normoglycaemia, which may itself be responsible for the lowering of hypoglycaemia awareness2 In the Netherlands no rise in the number of admissions for severe hypoglycaemia has been reported. On the contrary, the information centre on hospital admissions recorded a decrease in the number of admissions for severe hypoglycaemia during 1983-88, the period when the market share of human insulin increased from 4-1% to 82.1%
These data conflict with those of Egger and Teuscher. The main reason for this discrepancy might be the fact that our data are less likely than theirs to be affected by factors such as changes in blood glucose control since they are derived from data for the whole country, including university centres and non-specialist clinics. Although there may be a difference in the effects of human porcine insulin on the counterregulatory response to hypoglycaemia, there is still no evidence for a causal relation between the use of human insulin and the risk of severe
hypoglycaemia. Polyclinic Inwendige Geneeskunde, Academisch Ziekenhuis, Free University, 1081 HV Amsterdam, Netherlands 1. Heine RJ, Van der Heyden
R. J. HEINE E. A.
VAN DER
VEEN
EAP, Van der Veen EA. Responses to human and porcine insulin in healthy subjects. Lancet 1989; ii: 946-48. 2. Amiel SA, Sherwin RS, Simonson DC, Tamborlane WV. Effects of intensive insulin therapy on glycaemic thresholds for counterregulatory hormone release. Diabetes 1988; 37: 901-07.
BLOOD PROTEIN CAND PROTEIN S MEASUREMENTS IN INFANT AND PARENTS
have led
to self-immunisation, accounting for the raised LPS antibody concentrations. Part of the benefit of severe physical training might therefore be
the induction of LPS antibodies which could reduce any endotoxaemia caused by physical heat stress, as you suggest. It remains to be seen whether the "doping" of an athlete with parenteral administration of anti-LPS IgG leads to his improved performance in a medium to long-distance race or in a soccer game on a warm day. If so, miners, pilots, soldiers, and possibly racehorses, might also benefit. -Normai
range (/m!)
in aamts snown m
parentneses
deficiency diagnosed. The thrombosis can be controlled by oral warfarin and cyroprecipitate transfusion every other day. daily To our knowledge this report is the first of homozygous PS deficiency associated with neonatal purpura fulminans. The treatment seems to be life-long replacement therapy, and fresh frozen plasma is planned to replace cryoprecipitate when the patient grows older. PS concentrate, the ideal treatment for this baby, is not yet available in Thailand. was
Department of Paediatrics, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado, USA
CHULARATANA MAHASANDANA VINAI SUVATTE RICHARD A. MARLAR MARILYN J. MANCO-JOHNSON LINDA J. JACOBSON WILLIAM E. HATHAWAY
HE, Katz J, Marble R, Griffin JH. Inherited protein C deficiency and coumarin responsive chronic relapsing purpura fulminans in a newborn infant. Lancet 1983; ii: 1165-68. 2. Seligsohn U, Berger A, Abend M, et al. Homozygous protein C deficiency manifested by massive venous thrombosis in the newborn. N Engl J Med 1984; 310: 559-62. 3. Marciniak E, Wilson HD, Marlar RA. Neonatal purpura fulminans: a genetic disorder related to the absence of protein C in blood. Blood 1985; 65: 15-20. 4. Yuen P, Cheung A, Lin HJ, et al. Purpura fulminans in a Chinese boy with congenital protein C deficiency. Pediatrics 1986; 77: 670-76. 5. Manco-Johnson MJ, Marlar RA, Jacobson LJ, Hays T, Warady BA. Severe protein C deficiency in newborn infants. J Pediatr 1988; 113: 359-63. 6. Marlar RA, Montgomery RR, Broekmans AW. Diagnosis and treatment of homozygous protein C deficiency. J Pediatr 1989; 114: 528-34. 7 Comp PC, Nixon RR, Cooper R, Esmon CT. Familial protein S deficiency is associated with recurrent thrombosis. J Clin Invest 1984; 74: 2082-88. 8. Comp PC, Doray D, Patton D, Esmon CT. An abnormal plasma distribution of protein S occurs in functional protein S deficiency. Blood 1986; 67: 504. 1. Branson
Endotoxins in heatstroke SIR,-Indirect evidence supports your suggestion (Nov 4, p 1137) that inducing high levels of antibodies to lipopolysaccharide (LPS) is beneficial in the treatment of heat stress. 81 % of competitors in an ultramarathon (89-5 km) who collapsed along the way or were carried to the medical tent at the finishing line, had raised plasma LPS concentrations (including two in the reported lethal range). They also had high indices of nausea/vomiting/diarrhoeasymptoms produced by LPS-and they needed hours to days to recover. The remaining 19% with LPS in the normal range had far fewer and less severe episodes of nausea, vomiting, and diarrhoea, and they recovered within minutes to an hour or two. Those with low concentrations of plasma LPS had high levels of "natural" LPS IgG antibodies and vice versa. In the group of runners who managed to finish the race before collapsing, those with the lowest LPS and highest anti-LPS IgG concentrations performed betterie, they finished sooner. Racehorses, too, showed rises in LPS at the end of a stakes race .2 In a triathlon, athletes who trained the hardest (most miles jogged, bicycled, or swum) during the two weeks before the contest had the highest levels of natural anti-LPS IgG at the start of the race and lowest LPS concentrations at the end.3 Prolonged severe exercise may lead to periods of hypoxia, intestinal ischaemia, and raised body temperature. Short periods of expeirmental hypoxia,4 intestinal ischaemia,s or body temperature of 41-42°C6 led to the entry of large quantities of LPS into the circulation. This LPS may
Department of Physiology, University of Natal Medical School, Durban, South Africa
STEPHEN L. GAFFIN
JG, Gaffin SL, Wells MT, et al. Endotoxaemia in exhausted runners following a long distance race. S Afr Med J 1988; 73: 533-36. 2. Baker B, Gaffin SL, Wells MT, Brock-Utne JG. Endotoxaemia in race horses following exertion. J S Afr Vet Assoc 1988; 59: 63-66. 3. Bosenberg AT, Brock-Utne JG, Wells MTB, et al. Strenuous exercise causes systematic endotoxaemia. J Appl Physiol 1988; 65: 106-08. 4. Gaffin SL, Brock-Utne JG, Zanotti A, Wells MTB. Hypoxia induced endotoxemia in primates. Aviat Space Environ Med 1986; 57: 1044-49. 5. Gathiram P, Wells MT, Raidoo D, et al. Changes in plasma lipopolysaccharide concentrations in portal venous and systemic arterial blood during intestinal ischemia in primates. Circ Shock 1989; 27: 103-09. 6. Gathiram P, Wells MT, Raidoo D, et al. Portal and systemic plasma lipopolysaccharide concentrations in heat-stressed primates. Circ Shock 1988; 25: 1. Brock-Utne
223-30.
Human insulin and
hypoglycaemia
SIR,-Dr Egger and Dr Teuscher (Nov 25, p 1268) report that the introduction of human insulin in the Canton of Berne, Switzerland, caused a huge increase in admissions for severe hypoglycaemia to eight public hospitals during 1984-87. They attributed these cases of hypoglycaemia to a reduced awareness of hypoglycaemia, which may be partly caused by differences in counterregulatory responses to human and porcine insulin.1 The rise in the number of admissions seems to correlate quite well with the introduction of human insulin, but may also have been caused by other factors such as lowering of the mean HbA, value in the Canton of Berne in the pursuit of normoglycaemia, which may itself be responsible for the lowering of hypoglycaemia awareness2 In the Netherlands no rise in the number of admissions for severe hypoglycaemia has been reported. On the contrary, the information centre on hospital admissions recorded a decrease in the number of admissions for severe hypoglycaemia during 1983-88, the period when the market share of human insulin increased from 4-1% to 82.1%
These data conflict with those of Egger and Teuscher. The main reason for this discrepancy might be the fact that our data are less likely than theirs to be affected by factors such as changes in blood glucose control since they are derived from data for the whole country, including university centres and non-specialist clinics. Although there may be a difference in the effects of human porcine insulin on the counterregulatory response to hypoglycaemia, there is still no evidence for a causal relation between the use of human insulin and the risk of severe
hypoglycaemia. Polyclinic Inwendige Geneeskunde, Academisch Ziekenhuis, Free University, 1081 HV Amsterdam, Netherlands 1. Heine RJ, Van der Heyden
R. J. HEINE E. A.
VAN DER
VEEN
EAP, Van der Veen EA. Responses to human and porcine insulin in healthy subjects. Lancet 1989; ii: 946-48. 2. Amiel SA, Sherwin RS, Simonson DC, Tamborlane WV. Effects of intensive insulin therapy on glycaemic thresholds for counterregulatory hormone release. Diabetes 1988; 37: 901-07.
