- Email: [email protected]
FLUCTUATING SERUM CHOLESTEROL: IMPLICATIONS FOR CORONARY PREVENTION
404 RELEASE OF PAF-ACETHER AND PRECURSORS DURING ALLERGIC CUTANEOUS REACTIONS
SIR,-PAF-acether (PAF) is produced by and activates a wide variety of inflammatory cells.1 Its importance in allergic reactions has been supported by clinical observations. This phospholipid is one of the most potent agents inducing eosinophil chemotaxis and activation in vitro.2 In healthy volunteers, intradermal application of PAF elicits a biphasic inflammatory response with an acute wheal-and-flare reaction reminiscent of that induced by antigen in sensitised individuals and a later appearing neutrophil infiltration when PAF is injected or applied to the skin.3,4 Intradermal injection in atopic patients elicits an immediate wheal-and-flare response and an intense eosinophil infiltrate.s The PAF-induced eosinophil recruitment is comparable to the antigen-induced one in the same atopic individuals. Coupled with enhanced PAF biosynthesis in eosinophils from allergic patients6 these data suggest that atopic patients differ from non-atopic individuals in their response to PAF. We have shown that prolonged contact of allergen with the dermis of atopic volunteers induces an intense eosinophil recruitment and the appearance ofPAF.7 This led us to investigate whether or not the eosinophil infiltrate observed was associated with the release of PAF and its precursors during allergen-induced cutaneous
reaction in vivo.
pollen-sensitive patients (two females, four males, aged 20-26) were investigated. Sterile skin chambers overlying blister base sites were filled for 6 h with 1 ml of pollen diluted in Hanks balanced salt solution at a concentration that when intradermally injected induced a significant wheal-and-flare reaction or with the pollen vehicle only (control). The liquids were collected after 30 min and replaced by fresh solutions. 6 h later the liquids were withdrawn again. To study late events the chambers were filled with Hanks balanced salt solution until the morning of the next day. 24 h after the first introduction of the solutions into the chambers the liquids were collected and the chambers were removed. Sterile glass coverslips were taped over the blister sites and changed hourly for Six
TABLE
DERMIS AFI’ER VEHICLE AND POLLEN CHALLENGE 1
Results
material recovered from the chambers was further characterised as PAF: by inhibition of the platelet aggregation it induced by specific PAF receptor antagonists (BN 52021 [IHB] and L652,731 [MSD]); abolition of platelet aggregation after incubation with phospholipase A2 but not with lipase Al; and retention time on high-pressure liquid chromatography. The coverslips were airdried and stained with May-Grunwald-Giemsa. The percentages of various cell types were established from at least 500 cells counted with an optical microscope. At the sixth hour the amount of PAF (and PAF precursors) detected in pollen-containing chambers was increased (table I) and after 24 h, even though no allergen had been present for 18 h, we detected high amounts of PAF. Numerous eosinophils were recruited 24 h after pollen deposition on the superficial dermis but hardly any eosinophils were detected in the controls-(table II).
are mean
.
--
-
I-
,-,
,.
% (SEM) (n = 6).
These findings show that PAF is released during anaphylactic skin reactions to specific antigen in sensitive patients. When pollen was applied in the same way to the skin of normal volunteers no PAF enhancement ensued (data not shown). In pollen-sensitive patients, PAF appeared during the late phase of the reaction and persisted for at least 18 h after the allergen had been removed. Such PAF release may be closely related to the intense eosinophil recruitment observed after pollen since PAF is chemotactic for
eosinophils. The cellular origin of PAF has yet to be established. One candidate is the mast cell. However, our findings suggest that mast cell products released within the dermis might activate neutrophils, eosinophils, and/or macrophages to generate PAF at the cutaneous reaction site. Our results do demonstrate that PAF is released during late-phase cutaneous IgE-dependent allergic reactions and might account for allergic inflammatory events. INSERM Unit 312,
Department of Dermatology, Hôpital Henri Mondor, 94010 Créteil, France; and INSERM Unit 200,
Clamart, France
L. MICHEL Y. DENIZOT Y. THOMAS J. BENVENISTE L. DUBERTRET
R, Tencé M, Mencia-Huerta JM, Arnoux B, Ninio E, Benveniste J. A chemically defined monokine. macrophage-derived platelet-activating factor. In: Pick E, ed. Lymphokines: Vol VIII. New York: Academic Press, 1983: 249. Wardlaw AJ, Moqbel R, Cromwell O, Kay AB. Platlet-activating factor: a potent chemotactic and chemokinetic factor for human eosinophils.J Clin Invest 1986; 78: 1701-06. Archer CB, Page CP, Morley J, MacDonald DM. Accumulation of inflammatory cells in response to intracutaneous platelet-activating factor (Paf-acether) in man. Br J Dermatol 1985; 112: 285-90. Michel L, Mencia-Huerta J-M, Benveniste J, Dubertret L. Biologic properties of LTB4 and paf-acether in vivo in human skin. J Invest Dermatol 1987; 88: 675-81. Henock E, Vargaftig BB. Accumulation of eosinophils in response to intracuianeous PAF-acether and allergens in man. Lancet 1986; i: 1378-79. Lee TC, Lenihan DJ, Malone B, Roddy LL. Wasserman SI. Increased biosynthesis of platelet-activating factor in activated human eosinophils. J Biol Chem 1984; 259: 5526-30. Michel L, DeVos C, Rihoux J-P, Burtin C, Benveniste J, Dubertret L. Inhibitory effect of oral Cetirizine on in vivo antigen-induced histamine and paf-acether release and eosinophil recruitment in human skin. J Allergy Clin Immunol (m
1. Roubin
2.
6 hours.
Samples were processed and assessed for PAF by platelet aggregation assay.8 PAF precursors were expressed as PAF equivalents after alkaline hydrolysis and/or acetylation.9 The
II-PERCENTAGE OF EOSINOPHILS RECRUITED ON THE
3.
4. 5.
6.
7.
press). 8. Cazenave
JP, Benveniste J, Mustard JF. Aggregation of rabbit platelets by platelet-activating factor is independent of the release reaction and the arachidonate pathway and inhibited by membrane-active drugs. Lav Invest 1979; 41: 275-85. 9. Jouvin-Marche E, Ninio E, Beaurain G, Tencé M, Niaudet P, Benveniste J Biosynthesis of paf-acether (platelet-activating factor) VII: Precursors of pafacether and acetyl-transferase activity in human leukocytes. J Immunol 1984; 133: 892-98.
FLUCTUATING SERUM CHOLESTEROL: IMPLICATIONS FOR CORONARY PREVENTION
TABLE I-LEVELS OF PAF AND PAF PRECURSORS DETECTED IN
LIQUID FROM SKIN CHAMBERS CONTAINING VEHICLE OR POLLEN AND APPLIED TO POLLEN-SENSITIVE PATIENTS
in ngfmIlcm2, are mean (SEM) (n = 6). *Lyso-PAF l-0-atkyt-m-g!ycero-3-phosphocho!ine, I -alkyl-2-acyl-GPC =l-0-alkyl2-acyl-sn-glycero-3-phosphocholme.
Results,
=
SIR,-Awareness of the risks of having a raised serum cholesterol is rapidly spreading throughout America because of intensive media attention. The Framingham Study predicts that a 10% fall in cholesterol will be associated with a 20% decrease in coronary events,! and such data have led to calls2 for nationwide efforts to reduce cholesterol levels below 200 mg/dl for adults. However, differences in serum cholesterol in the same individual may be extreme enough to make it impossible to assess his or her risk on the basis of only one sample.3,4 Because many blood-borne elements have fast frequency fluctuations over time,S,6 we hypothesised that similar fluctuations might exist for this serum cholesterol, whose levels are commonly thought to be very stable. To test this, we sampled blood every 20 min for a 6 h period from one fasting subject confined to a chair, and measured serum cholesterol levels. Mean coefficient of assay variation, based on four of the samples done blindly in triplicate, was less than 1-5%.
405
Serum cholesterol concentrations measured volunteer.
over
6 h in seated
Cholesterol levels over the 6 h study varied from a nadir of 189 to peak of 211 mg/dl (figure). Had just these two samples been collected, the data would have indicated a difference in risk of coronary artery disease of over 20%. Spectral analysis of detrended data6 revealed peak fast frequency fluctuation at a period of one cycle every 50 min. 8 of 19 samples were over 200 mg/dl. Had one of those samples been collected and a repeat test confirmatory of such "elevated" levels, this individual would have been given dietary counselling and would have been called back to his doctor in a year for retesting. But if one of the "normal" 11samples had been collected, this individual would have been told that his serum cholesterol was fme and did not need to be checked again for 5 years. The difference in personal and financial cost between these two outcomes is considerable. This one set of data shows the problems inherent in moving epidemiological data to the individual patient. Nationwide implementation of cholesterol-lowering strategies probably should await work designed to understand and, if possible, lessen the fluctuation in levels that occur in even carefully controlled experimental situations such as the one used here.
CHD (121 mg/dl) (p<001, by paired t test, both on untransformed and on log-transformed data). Analysis on untransformed data gave a 95% confidence interval for the population mean difference of 4 3-27-3 mg/dl. Lp(a) may help to explain the considerable heterogeneity exhibited by patients with familial hypercholesterolaemia. A posible explanation for the atherogenicity of Lp(a) lies in the striking molecular homology between Lp(a) and plasminogen.1,2 Domains of plasminogen have been implicated in fibrin binding to endothelial cells and similar domains have been identified within apo(a) together with a region of serine protease activity. Apo(a) could therefore direct Lp(a) particles to sites of fibrin deposition (vascular injury) providing a high concentration of cholesterol-rich lipoprotein which would be taken up by macrophages via their acetyl-low-density-lipoprotein receptors; this process underlies the formation of macrophage-derived foam cells, a characteristic of atherosclerotic plaques.
a
BENJAMIN H. NATELSON Divisions of Neurology, Research, and Pathology, VA Medical Center, East Orange, New Jersey 07019, USA
WALTER N. TAPP ANAND MUNSIF WILBUR BURNS
We suggest that measuring Lp(a) in individuals with familial hypercholesterolaemia may help to evaluate their CHD risk. Nicotinic acid and neomycin significantly reduce Lp(a) concentrations,3 though it remains to be shown whether changes in
its concentrations
are
associated with lessened incidence of CHD. R. HOULSTON
1. National Heart,
2 3 4. 5
6.
Lung, and Blood Institute Lipid Research Clinics Coronary Primary Prevention Trial. Results II: The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984; 251: 365-74. Dalen JE. Lowering serum cholesterol: It is time to proceed. Arch Intern Med 1988; 148: 34-35. Hegsted DM, Nicolosi RJ. Individual variation in serum cholesterol levels. Proc Natl Acad Sci USA 1987; 84: 6259-61. Roberts L. Measuring cholesterol is as tricky as lowering it. Science 1987; 238: 482-83. Levin BE, Rappaport M, Natelson BH. Ultradian variations of plasma noradrenaline in humans. Life Sci 1979; 25: 621-28. Tapp WN, Holday J, Natelson BH. Ultradian glucocorticoid rhythms in monkeys and rats continue during stress. Am J Physiol 1984, 247: R866-71.
Lp(a) levels in individuals with familial hypercholesterolaemia with and without CHD (means shown).
Division of Chemical Pathology and Metabolic Disorders, United Medical Schools of Guy’s and St St Thomas’ Hospital, London SE1 7EH
SIR,-We have done a case-control study of the relation between
lipoprotein (a) (Lp[a]) and coronary heart disease (CHD) in 24 patients with familial hypercholesterolaemia. While this disorder is associated with a large increase in the frequency of CHD, often in early adult life, patients with familial hypercholesterolaemia are strikingly heterogeneous in respect of the occurrence and age of presentation of CHD. Since Lp(a) is directly related to the incidence of CHD in the normal population we have investigated the possibility that its concentration can modulate the development of CHD in patients with familial hypercholesterolaemia. women and 16 men aged 30-58 (12 with and 12 without CHD clinical criteria and exercise ECG findings) were studied. Lp(a) was measured by an automated immunochemical procedure. The two groups were matched for age, sex, current smoking, and
8
on
hypertension. The
mean
(27.9mg/dl)
Lp(a) concentration (figure) in patients with CHD significantly greater than that in those without
was
J. QUINEY J. MOUNT G. F. WATTS B. LEWIS
DL, Fless GM, Kohn WJ, McLean JW, et al. Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen. Proc Natl Acad Sci
1. Eaton
USA 1987; 84: 3224-28. 2. McLean JW, Tomlinson JE, Krang W. 3.
LIPOPROTEIN (a) AND CORONARY HEART DISEASE IN FAMILIAL HYPERCHOLESTEROLAEMIA
Thomas’s,
et
al. cDNA sequence of human
apolipoprotein(a) is homologous to plasminogen. Nature 1987; 330: 132-37. Gurakar A, Hoeg JM, Kostner G, Papadopoulos NM, Brewer HB Jr. Levels of lipoprotein LP(a) decline with neomycin and niacin treatment. Atherosclerosis 1985; 57: 293-301.
PREVENTION OF POST-TRANSFUSION INFECTIOUS COMPLICATIONS
SIR,-Dr Conrad (July 23, p 217) discusses two possible strategies for reducing the hazard of post-transfusion non-A, non-B (NANB) hepatitis-namely, immune serum gammaglobulin (ISG) or the exclusion of blood donors on the basis of "non-specific identifiers which place them at greater risk". These identifiers could be, for example, social characteristics and/or laboratory findings. Conrad favours ISG, mainly because the second approach would seem to diminish seriously the donor pool. Levels of neopterin are raised, with a high sensitivity, in NANB hepatitis.1.2 Neopterin, produced by monocytes/macrophages upon stimulation with interferon-y, is easy to measure in body fluids and provides a non-invasive tool to assess the activation state of cell-mediated immunity in vivo. Neopterin levels are raised, with high sensitivity, in people with virus infections, intracellular
SIR,-PAF-acether (PAF) is produced by and activates a wide variety of inflammatory cells.1 Its importance in allergic reactions has been supported by clinical observations. This phospholipid is one of the most potent agents inducing eosinophil chemotaxis and activation in vitro.2 In healthy volunteers, intradermal application of PAF elicits a biphasic inflammatory response with an acute wheal-and-flare reaction reminiscent of that induced by antigen in sensitised individuals and a later appearing neutrophil infiltration when PAF is injected or applied to the skin.3,4 Intradermal injection in atopic patients elicits an immediate wheal-and-flare response and an intense eosinophil infiltrate.s The PAF-induced eosinophil recruitment is comparable to the antigen-induced one in the same atopic individuals. Coupled with enhanced PAF biosynthesis in eosinophils from allergic patients6 these data suggest that atopic patients differ from non-atopic individuals in their response to PAF. We have shown that prolonged contact of allergen with the dermis of atopic volunteers induces an intense eosinophil recruitment and the appearance ofPAF.7 This led us to investigate whether or not the eosinophil infiltrate observed was associated with the release of PAF and its precursors during allergen-induced cutaneous
reaction in vivo.
pollen-sensitive patients (two females, four males, aged 20-26) were investigated. Sterile skin chambers overlying blister base sites were filled for 6 h with 1 ml of pollen diluted in Hanks balanced salt solution at a concentration that when intradermally injected induced a significant wheal-and-flare reaction or with the pollen vehicle only (control). The liquids were collected after 30 min and replaced by fresh solutions. 6 h later the liquids were withdrawn again. To study late events the chambers were filled with Hanks balanced salt solution until the morning of the next day. 24 h after the first introduction of the solutions into the chambers the liquids were collected and the chambers were removed. Sterile glass coverslips were taped over the blister sites and changed hourly for Six
TABLE
DERMIS AFI’ER VEHICLE AND POLLEN CHALLENGE 1
Results
material recovered from the chambers was further characterised as PAF: by inhibition of the platelet aggregation it induced by specific PAF receptor antagonists (BN 52021 [IHB] and L652,731 [MSD]); abolition of platelet aggregation after incubation with phospholipase A2 but not with lipase Al; and retention time on high-pressure liquid chromatography. The coverslips were airdried and stained with May-Grunwald-Giemsa. The percentages of various cell types were established from at least 500 cells counted with an optical microscope. At the sixth hour the amount of PAF (and PAF precursors) detected in pollen-containing chambers was increased (table I) and after 24 h, even though no allergen had been present for 18 h, we detected high amounts of PAF. Numerous eosinophils were recruited 24 h after pollen deposition on the superficial dermis but hardly any eosinophils were detected in the controls-(table II).
are mean
.
--
-
I-
,-,
,.
% (SEM) (n = 6).
These findings show that PAF is released during anaphylactic skin reactions to specific antigen in sensitive patients. When pollen was applied in the same way to the skin of normal volunteers no PAF enhancement ensued (data not shown). In pollen-sensitive patients, PAF appeared during the late phase of the reaction and persisted for at least 18 h after the allergen had been removed. Such PAF release may be closely related to the intense eosinophil recruitment observed after pollen since PAF is chemotactic for
eosinophils. The cellular origin of PAF has yet to be established. One candidate is the mast cell. However, our findings suggest that mast cell products released within the dermis might activate neutrophils, eosinophils, and/or macrophages to generate PAF at the cutaneous reaction site. Our results do demonstrate that PAF is released during late-phase cutaneous IgE-dependent allergic reactions and might account for allergic inflammatory events. INSERM Unit 312,
Department of Dermatology, Hôpital Henri Mondor, 94010 Créteil, France; and INSERM Unit 200,
Clamart, France
L. MICHEL Y. DENIZOT Y. THOMAS J. BENVENISTE L. DUBERTRET
R, Tencé M, Mencia-Huerta JM, Arnoux B, Ninio E, Benveniste J. A chemically defined monokine. macrophage-derived platelet-activating factor. In: Pick E, ed. Lymphokines: Vol VIII. New York: Academic Press, 1983: 249. Wardlaw AJ, Moqbel R, Cromwell O, Kay AB. Platlet-activating factor: a potent chemotactic and chemokinetic factor for human eosinophils.J Clin Invest 1986; 78: 1701-06. Archer CB, Page CP, Morley J, MacDonald DM. Accumulation of inflammatory cells in response to intracutaneous platelet-activating factor (Paf-acether) in man. Br J Dermatol 1985; 112: 285-90. Michel L, Mencia-Huerta J-M, Benveniste J, Dubertret L. Biologic properties of LTB4 and paf-acether in vivo in human skin. J Invest Dermatol 1987; 88: 675-81. Henock E, Vargaftig BB. Accumulation of eosinophils in response to intracuianeous PAF-acether and allergens in man. Lancet 1986; i: 1378-79. Lee TC, Lenihan DJ, Malone B, Roddy LL. Wasserman SI. Increased biosynthesis of platelet-activating factor in activated human eosinophils. J Biol Chem 1984; 259: 5526-30. Michel L, DeVos C, Rihoux J-P, Burtin C, Benveniste J, Dubertret L. Inhibitory effect of oral Cetirizine on in vivo antigen-induced histamine and paf-acether release and eosinophil recruitment in human skin. J Allergy Clin Immunol (m
1. Roubin
2.
6 hours.
Samples were processed and assessed for PAF by platelet aggregation assay.8 PAF precursors were expressed as PAF equivalents after alkaline hydrolysis and/or acetylation.9 The
II-PERCENTAGE OF EOSINOPHILS RECRUITED ON THE
3.
4. 5.
6.
7.
press). 8. Cazenave
JP, Benveniste J, Mustard JF. Aggregation of rabbit platelets by platelet-activating factor is independent of the release reaction and the arachidonate pathway and inhibited by membrane-active drugs. Lav Invest 1979; 41: 275-85. 9. Jouvin-Marche E, Ninio E, Beaurain G, Tencé M, Niaudet P, Benveniste J Biosynthesis of paf-acether (platelet-activating factor) VII: Precursors of pafacether and acetyl-transferase activity in human leukocytes. J Immunol 1984; 133: 892-98.
FLUCTUATING SERUM CHOLESTEROL: IMPLICATIONS FOR CORONARY PREVENTION
TABLE I-LEVELS OF PAF AND PAF PRECURSORS DETECTED IN
LIQUID FROM SKIN CHAMBERS CONTAINING VEHICLE OR POLLEN AND APPLIED TO POLLEN-SENSITIVE PATIENTS
in ngfmIlcm2, are mean (SEM) (n = 6). *Lyso-PAF l-0-atkyt-m-g!ycero-3-phosphocho!ine, I -alkyl-2-acyl-GPC =l-0-alkyl2-acyl-sn-glycero-3-phosphocholme.
Results,
=
SIR,-Awareness of the risks of having a raised serum cholesterol is rapidly spreading throughout America because of intensive media attention. The Framingham Study predicts that a 10% fall in cholesterol will be associated with a 20% decrease in coronary events,! and such data have led to calls2 for nationwide efforts to reduce cholesterol levels below 200 mg/dl for adults. However, differences in serum cholesterol in the same individual may be extreme enough to make it impossible to assess his or her risk on the basis of only one sample.3,4 Because many blood-borne elements have fast frequency fluctuations over time,S,6 we hypothesised that similar fluctuations might exist for this serum cholesterol, whose levels are commonly thought to be very stable. To test this, we sampled blood every 20 min for a 6 h period from one fasting subject confined to a chair, and measured serum cholesterol levels. Mean coefficient of assay variation, based on four of the samples done blindly in triplicate, was less than 1-5%.
405
Serum cholesterol concentrations measured volunteer.
over
6 h in seated
Cholesterol levels over the 6 h study varied from a nadir of 189 to peak of 211 mg/dl (figure). Had just these two samples been collected, the data would have indicated a difference in risk of coronary artery disease of over 20%. Spectral analysis of detrended data6 revealed peak fast frequency fluctuation at a period of one cycle every 50 min. 8 of 19 samples were over 200 mg/dl. Had one of those samples been collected and a repeat test confirmatory of such "elevated" levels, this individual would have been given dietary counselling and would have been called back to his doctor in a year for retesting. But if one of the "normal" 11samples had been collected, this individual would have been told that his serum cholesterol was fme and did not need to be checked again for 5 years. The difference in personal and financial cost between these two outcomes is considerable. This one set of data shows the problems inherent in moving epidemiological data to the individual patient. Nationwide implementation of cholesterol-lowering strategies probably should await work designed to understand and, if possible, lessen the fluctuation in levels that occur in even carefully controlled experimental situations such as the one used here.
CHD (121 mg/dl) (p<001, by paired t test, both on untransformed and on log-transformed data). Analysis on untransformed data gave a 95% confidence interval for the population mean difference of 4 3-27-3 mg/dl. Lp(a) may help to explain the considerable heterogeneity exhibited by patients with familial hypercholesterolaemia. A posible explanation for the atherogenicity of Lp(a) lies in the striking molecular homology between Lp(a) and plasminogen.1,2 Domains of plasminogen have been implicated in fibrin binding to endothelial cells and similar domains have been identified within apo(a) together with a region of serine protease activity. Apo(a) could therefore direct Lp(a) particles to sites of fibrin deposition (vascular injury) providing a high concentration of cholesterol-rich lipoprotein which would be taken up by macrophages via their acetyl-low-density-lipoprotein receptors; this process underlies the formation of macrophage-derived foam cells, a characteristic of atherosclerotic plaques.
a
BENJAMIN H. NATELSON Divisions of Neurology, Research, and Pathology, VA Medical Center, East Orange, New Jersey 07019, USA
WALTER N. TAPP ANAND MUNSIF WILBUR BURNS
We suggest that measuring Lp(a) in individuals with familial hypercholesterolaemia may help to evaluate their CHD risk. Nicotinic acid and neomycin significantly reduce Lp(a) concentrations,3 though it remains to be shown whether changes in
its concentrations
are
associated with lessened incidence of CHD. R. HOULSTON
1. National Heart,
2 3 4. 5
6.
Lung, and Blood Institute Lipid Research Clinics Coronary Primary Prevention Trial. Results II: The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984; 251: 365-74. Dalen JE. Lowering serum cholesterol: It is time to proceed. Arch Intern Med 1988; 148: 34-35. Hegsted DM, Nicolosi RJ. Individual variation in serum cholesterol levels. Proc Natl Acad Sci USA 1987; 84: 6259-61. Roberts L. Measuring cholesterol is as tricky as lowering it. Science 1987; 238: 482-83. Levin BE, Rappaport M, Natelson BH. Ultradian variations of plasma noradrenaline in humans. Life Sci 1979; 25: 621-28. Tapp WN, Holday J, Natelson BH. Ultradian glucocorticoid rhythms in monkeys and rats continue during stress. Am J Physiol 1984, 247: R866-71.
Lp(a) levels in individuals with familial hypercholesterolaemia with and without CHD (means shown).
Division of Chemical Pathology and Metabolic Disorders, United Medical Schools of Guy’s and St St Thomas’ Hospital, London SE1 7EH
SIR,-We have done a case-control study of the relation between
lipoprotein (a) (Lp[a]) and coronary heart disease (CHD) in 24 patients with familial hypercholesterolaemia. While this disorder is associated with a large increase in the frequency of CHD, often in early adult life, patients with familial hypercholesterolaemia are strikingly heterogeneous in respect of the occurrence and age of presentation of CHD. Since Lp(a) is directly related to the incidence of CHD in the normal population we have investigated the possibility that its concentration can modulate the development of CHD in patients with familial hypercholesterolaemia. women and 16 men aged 30-58 (12 with and 12 without CHD clinical criteria and exercise ECG findings) were studied. Lp(a) was measured by an automated immunochemical procedure. The two groups were matched for age, sex, current smoking, and
8
on
hypertension. The
mean
(27.9mg/dl)
Lp(a) concentration (figure) in patients with CHD significantly greater than that in those without
was
J. QUINEY J. MOUNT G. F. WATTS B. LEWIS
DL, Fless GM, Kohn WJ, McLean JW, et al. Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen. Proc Natl Acad Sci
1. Eaton
USA 1987; 84: 3224-28. 2. McLean JW, Tomlinson JE, Krang W. 3.
LIPOPROTEIN (a) AND CORONARY HEART DISEASE IN FAMILIAL HYPERCHOLESTEROLAEMIA
Thomas’s,
et
al. cDNA sequence of human
apolipoprotein(a) is homologous to plasminogen. Nature 1987; 330: 132-37. Gurakar A, Hoeg JM, Kostner G, Papadopoulos NM, Brewer HB Jr. Levels of lipoprotein LP(a) decline with neomycin and niacin treatment. Atherosclerosis 1985; 57: 293-301.
PREVENTION OF POST-TRANSFUSION INFECTIOUS COMPLICATIONS
SIR,-Dr Conrad (July 23, p 217) discusses two possible strategies for reducing the hazard of post-transfusion non-A, non-B (NANB) hepatitis-namely, immune serum gammaglobulin (ISG) or the exclusion of blood donors on the basis of "non-specific identifiers which place them at greater risk". These identifiers could be, for example, social characteristics and/or laboratory findings. Conrad favours ISG, mainly because the second approach would seem to diminish seriously the donor pool. Levels of neopterin are raised, with a high sensitivity, in NANB hepatitis.1.2 Neopterin, produced by monocytes/macrophages upon stimulation with interferon-y, is easy to measure in body fluids and provides a non-invasive tool to assess the activation state of cell-mediated immunity in vivo. Neopterin levels are raised, with high sensitivity, in people with virus infections, intracellular