- Email: [email protected]
INTRALIPID AND RETICULOENDOTHELIAL BLOCKADE
1138 We would be interested if others have observed ulnar nerve palsies in patients with Cimino-Brescia fistulae since awareness of the syndrome and its possible xtiology might have prevented the dysfunction experienced by the third patient.
ORGAN UPTAKE OF TEST PARTICLES
D. V. HAMILTON Addenbrooke’s Hospital, Cambridge CB2 2QQ
D. B. EVANS R.G.HENDERSON
WARM-UP PHENOMENON IN ANGINA PECTORIS
SIR,—Dr Jaffe and Ms Quinn (Nov. 1, p. 934) record the effect of exercise-induced modulation of exercise testing in angina. In a less objective manner I can confirm their findings of alleviation of ischaemic pain by prior exercise. After mild angina I have been carrying out some personal assessments on a bicycle ergometer at home and I noticed that consecutive periods of exercise, with very short rest intervals, become progressively longer for the same workload:
*Results expressed as ND=Not done
mean
±SEM.
.
I should like to add one fact which may help in exercise evaluation in angina. There is a noticeable and consistent ability to carry a heavier and more sustained workload when the test is carried out immediately after rising, compared with a test immediately before going to bed. For the same total workload, applied at the same rate of working, retrosternal pain occurs sooner when tested in the evening. The mean time to evoke symptoms in the morning exercise was 5 6 min, compared with 4 2 min during evening exercise. Therefore it may be important to test patients at the same time of day when they are being assessed over long periods of time. Biochemistry Department, Gartnavel General Hospital, 1053 Great Western 12 0YN
Glasgow G
Road,
L. B. ROBERTS
in
dramatic reduction in hepatic Kupffer-cell clearance of CrSRBC, with spillover into the spleen.’ In contrast there was no alteration in the distribution of Tc-sulphur colloid, as reported previously.3 In mice pretreated with intralipid there was no evidence of impairment of RE blood clearance as measured by organ distribution of either Cr-SRBC or Tc-sulphur colloid. Intravenous infusion of fat emulsions can cause RE blockade in animals.4 In man, intralipid can accumulate in Kupffer cellsand in the spleen;pigment accumulation in Kupffer cells is a characteristic finding after long-term infusions.7 But these present experiments have failed to show any evidence of RE blockade after large intravenous doses of intralipid. Similarly in man, RE blockade was not recorded after intralipid.’ Thus, there is no evidence to substantiate the fear that intralipid causes RE blockade. a
Department of Pathology, Medical School, Bristol B58 1TD
INTRALIPID AND RETICULOENDOTHELIAL BLOCKADE
SIR,—Dr Fischer and colleagues (Oct. 18, p.819) report that the pretreatment of mice with intraperitoneal (i.p.) ’Intralipid’ results in an increase in death rate and in bacteraemia after challenge with i.p. streptococci, and that these changes are associated with decreased neutrophil chemotaxis. However, they imply in the same paper that part of the diminution in bacterial defences caused by intralipid might be due to reticuloendothelial (RE) blockade. I here report experiments done to find out whether intralipid causes RE blockade in mice. ICR mice were injected intravenously with large doses of intralipid 10% (Cutter Laboratories). A volume of 0 - 5 ml in a mouse is equivalent, weight for weight, to 1 5 1 in a 70 kg man. After varying intervals, one of two labelled test particles was injected intravenously: 5 x 107 5’Cr-labelled sheep red blood cells (CrSRBC) were used to assess possible blockade of RE-dependent blood clearance as described previouslyl or 99mTc-sulphur colloid (’Tesuloid’, Squibb) was given in an equivalent dose to that used clinically because of reports that patients with hyperlipoproteinaemia show decreased hepatic RE uptake of this agent.2Other mice were pretreated with 500 mg dextran sulphate intravenously to cause RE blockade. Control mice were pretreated with 0. 5 ml saline. All groups were killed 2 h after receiving test labelled particles. The results are in the accompanying table. As expected, in control mice about 90% of the Cr-SRBCl or Tcsulphur colloidwas recovered from the liver, and less than 5% from the spleen. In dextran-sulphate-treated mice RE blockade resulted 1.
Bradfield JWB, Souhami RL, Addison IE. The mechanism of the adjuvant effect of
sulphate Immunology 1974; 26: 383-92. BA, Bardfield PA, Bodian JE, Sugarman LA, Hellman L. Liver scans in hyperlipoproteinemia. JAMA 1974; 227: 907-10. 3. Bradfield JWB, Wagner HN, Jr. The relative importance of blood flow and liver phagocytic function in the distribution of 99mTc-sulfur colloid.J Nucl Med 1977; dextran
SIR,—Fischer et al. gave ’Intralipid’ intraperitoneallyto mice for 3 days, followed by streptococci; more treated mice died than untreated controls. However, the suggestion that the mechanism for this increased mortality was a blockade of the RES by intralipid seems unjustified. Studies in man shown no such effect.’ Instead another mechanism appears not to have been controlled for. This is a physicochemically induced increased permeability of the peritoneal membrane for bacteria by the repeated instillations ofintralipid. As Dr Gordon (Nov. 8, p. 1021) has pointed out Fischer et al. give no details about the handling of the control animals-were they given repeated intraperitoneal injections of solvent or glucose (the latter would be interesting since the alternative to alimentation with fats is carbohydrates)? If the effect was on permeability the results seem irrelevant. An intraperitoneal injection of intra lipid isa strange route of administration in human medicine. In their next experiment Fischer et al. exposed human neutrophils in vitro to considerably higher concentrations of intralipid than those achieved in clinical practice, where the highest blood concentrations seem to be around 8 mg/ml when recommendations for infusions are followed.Lower doses of intralipid than 12 5 mg/ml should be tested to obtain information relevant to the Luzio NR, Blickens DA. Influence of intravenously administered lipids on reticuloendothelial function. J Reticuloendothel Soc 1966; 3: 250-70. 5. Du Toit DF, Villet WT, Heydenrych T. Fat emulsion deposition in mononuclear phagocyte system. Lancer 1978; ii 898. 6. Forbes GB. Splenic lipidosis after administration of intravenous fat emulsion J Clin Pathol 1978; 31: 765-71. 7. Thompson SW The pathology of parenteral nutrition with lipids Springfield. Illinois Charles C. Thomas, 1974. 121-217, 679-745, 801-62. 8. Jarstrand C, Bergham L, Lahnborg G. Human granolocyte and reticuloendothelial system function during Intralipid infusion J Parenteral Enteral Nutr 1978. 2:
4. Di
2. Sachs
18: 620.
J. W. B. BRADFIELD
663-70. 1. 2.
Jarstrand C, Berghem L, Lahnborg G Human granulocyte and reticuloendithelial system function during Intralipid infusion. J Parent Ent Nutr 1978, 2: 663-70 Hallberg D. Elimination of exogenous lipids from the blood stream. Acta Physiol Scand 1965; 65 suppl 254.
1139 EFFECT OF INTRALIPID ON THE BACTERICIDAL CAPACITY OF
NEUTROPHILS AND ON MIGRATION UNDER AGAROSE AFTER STIMULATION WITH EITHER SERUM OR AN E. COLI BACTERIAL FACTOR
Values as meantSE (n= 10). *% bacteria living after incubation for 45 or 90 min. tMigration (mm) stimulated by serum or E. coli bacterial factor.
aim of the study-i.e., to find out if intralipid hampers bacterial defences in man. Other studies have yielded such information, 1,3 and the dose of intra lipid seems critical. We have studied ten healthy volunteers given 500 ml of 10% intralipid over 6 h. Blood for determination of neutrophil bactericidal capacity and migration under agarose4 was obtained before infusion, at its end, and 2 h after the discontinuation. Neutrophil function was not affected in conditions chosen to adhere closely to those at clinical practice (see table). Further carefully controlled studies are needed to find out if intralipid really does impair host defence.
JAN PALMBLAD
Department of Medicine 4, Södersjukhuset, S-100 64 Stockholm, Sweden
OLLE BROSTRÖM ANN-MARI UDEN
Department of Clinical Bacteriology, Södersjukhuset, Stockholm
NIKOS VENIZELOS
Department of Experimental Surgery, Thoracic Clinic, Karolinska Hospital, Stockholm
SIR,-Patients who
are
GORDON LAHNBORG
candidates for total
determine the effect of the various nutrients on the immune system. Leucocyte chemotaxis is an important function of the phagocytic system and defective chemotaxis predisposes to infection and sepsis.5In agreement with the report from Dr Fischer and his colleagues we found that incubation with ’Intralipid’ of leucocytes from normals depressed chemotactic migration.6 During the intravenous administration of this fat emulsion to normal chemotaxis decreased in close correlation with the degree of hypertriglyceridaemia induced. However, chemotactic migration always returned to normal 22 h after the infusion was stopped. Earlier studies from our group had shown that the degree of hypertriglyceridaemia during intralipid infusion in patients, correlates with the impairment of leucocyte function, as measured by bactericidal capacity and nitroblue tetrazolium (NBT) reduction. Furthermore granulocytes from patients with type IV 8 hyperlipoproteinaemia show a decrease in NBT reduction. Fischer et al. found that bacterial clearance is impaired after the intraperitoneal injection of intralipid in mice. Our studies in patients showed that neither the phagocytic nor the catabolic function 3 Nordenström J, Jarstrand C, Wiernik A. Decreased chemotactic and random migration of leukocytes during Intralipid infusion. Am J Clin Nutr 1979; 32: 2416-22. 4. Afzelius BA, Ewetz L, Palmblad J, Udén AM, Venizelos N. Structure and function of neutrophils from patients with the immotile cilia syndrome. Acta Med Scand 1980;
145-54.
5. Editorial. Disorders of neutrophil function. Lancet 1974; i: 438. 6. Nordenström J, Jarstrand C, Wiernik A. Decreased chemotactic and random migration
of leukocytes during Intralipid infusion. Am J Clin Nutr 1979; 32: 2416-22. C, Berghem L, Lahnborg G. Human granulocyte and reticulo-endothelial system function during Intralipid infusion. J Parent Ent Nutr 1978; 2: 663-70. 8. Jarstrand C, Angelin B, Einarsson K. Decreased nitroblue tetrazolium reduction of granulocytes in type IV hyperlipoproteinemia. J Lab Clin Med 1979; 94: 897-901. 7. Jarstrand
Departments of Surgery and Clinical Bacteriology, Karolinska Institute, Huddinge Hospital, S-141 86 Huddinge, Sweden
JÖRGEN NORDENSTRÖM CONNIE JARSTRAND DAG HALLBERG
parenteral nutrition
(TPN) are prone to infection, and catheter sepsis is one of the most feared complications of intravenous feeding. Thus, in evaluating the nutritional support of patients in need of TPN it is important to
208:
of the reticuloendothelial system (125I-microaggregated human serum albumin method) was significantly affected by intralipid infusion.7 Indeed intralipid may enhance some immune functions. Our later studies have shown an increased NBT reduction in monocytes from patients receiving intralipid. In experiments with such cells in vitro, we have also noted an increased phagocytosis of fluorescein-labelled yeast particles, an increased chemotactic and random migration, and increased NBT reduction. The same changes were also found in alveolar macrophages from rabbits after incubation with intralipid in vitro (C. Jarstrand and A. Wiernik, unpublished). Others9 have shown that intralipid may also cause a significantly increased response of human thymic lymphocytes to mitogens and antigens in vitro. Patients who cannot meet their energy requirements orally are candidates for TPN, supplied as hypertonic glucose solutions and aminoacids ("glucose system") or with part of the carbohydrate calories substituted by intravenous fat emulsions ("lipid system"). Plasma triglyceride levels are higher for the glucose system than for the lipid system. 10 Since we found that the impairment of leucocyte function is correlated to the degree ofhypertriglyceridaemia, it may be that, despite the finding that intralipid per se diminishes antibacterial defence, the clinical alternative, in which a larger proportion of glucose has to be given, has an equal or more depressive effect on leucocyte function. Fischer et al., drawing on studies in mice and in vitro studies on neutrophils from volunteers, suggest that "Intralipid may enhance the risk of bacterial sepsis in certain patients". Our studies and Fischer’s are inconclusive in this respect, and we do not agree with your Oct. 18 editorial that the observations discussed strengthen the case against the use of fat emulsions in patients. Before any strong recommendation against the clinical use of intralipid is made, studies should be done on the alternative (i.e., administration of a larger proportion of carbohydrate calories).
HDL AND CORONARY HEART DISEASE
SIR,—Dr Key’s caution about the interpretation of data on high density lipoprotein (HDL) are well taken. It.is certainly undemonstrated that raising the concentration of HDL reduces the risk of coronary heart disease (CHD); and prophylaxis based on such a premise is, at the very least, premature. Moreover, as he points out, cross-cultural data are sparse and difficult to interpret. The role of HDL in populations with low levels of total cholesterol remains to be evaluated. Instead of considering HDL by itself, however, it might be more appropriate to use, for an estimation of CHD risk, either a linear combination of HDL and LDL (or total cholesterol) or a ratio of the two, as we have suggested.2 If LDL is atherogenic and HDL is counter-atherogenic, the balance between the two may be more relevant than either alone. This may be especially important for older persons or for groups with low concentrations of total blood cholesterol. The data Keys presents on non-CHD death are interesting, although they do not accord with our observations.3But it is not clear why long-term follow-up is preferable to short-term. When the entire cohort is dead, it follows that, if persons dying of CHD had a DM, Copeland EM, Corriere JN, Richie ER, Jacobson K, Dudrick SJ. The effect soybean oil emulsion on lymphocyte transformation. J Parent Ent Nutr 1978; 2: 112-15. 10. Broviac JW, Riella MC, Scribner BH. The role of Intralipid in prolonged parenteral nutrition I As a caloric substitute for glucose. AmJ Clin Nutr 1976; 29: 255-57 1. Keys A. Alpha lipoprotein (HDL) cholesterol in the serum and the risk of coronary heart disease and death Lancet 1980; ii: 603. 2. Gordon T, Castelli WP, Hjortalnd MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease: The Framingham study. Am J Med 1977; 62: 707. 3. Gordon T, Kannel WB, Castelli WP, Dawber TR. Lipoproteins, cardiovascular disease and death: The Framingham study. Arch Intern Med (in press). 9. Ota
ofa 10%
ORGAN UPTAKE OF TEST PARTICLES
D. V. HAMILTON Addenbrooke’s Hospital, Cambridge CB2 2QQ
D. B. EVANS R.G.HENDERSON
WARM-UP PHENOMENON IN ANGINA PECTORIS
SIR,—Dr Jaffe and Ms Quinn (Nov. 1, p. 934) record the effect of exercise-induced modulation of exercise testing in angina. In a less objective manner I can confirm their findings of alleviation of ischaemic pain by prior exercise. After mild angina I have been carrying out some personal assessments on a bicycle ergometer at home and I noticed that consecutive periods of exercise, with very short rest intervals, become progressively longer for the same workload:
*Results expressed as ND=Not done
mean
±SEM.
.
I should like to add one fact which may help in exercise evaluation in angina. There is a noticeable and consistent ability to carry a heavier and more sustained workload when the test is carried out immediately after rising, compared with a test immediately before going to bed. For the same total workload, applied at the same rate of working, retrosternal pain occurs sooner when tested in the evening. The mean time to evoke symptoms in the morning exercise was 5 6 min, compared with 4 2 min during evening exercise. Therefore it may be important to test patients at the same time of day when they are being assessed over long periods of time. Biochemistry Department, Gartnavel General Hospital, 1053 Great Western 12 0YN
Glasgow G
Road,
L. B. ROBERTS
in
dramatic reduction in hepatic Kupffer-cell clearance of CrSRBC, with spillover into the spleen.’ In contrast there was no alteration in the distribution of Tc-sulphur colloid, as reported previously.3 In mice pretreated with intralipid there was no evidence of impairment of RE blood clearance as measured by organ distribution of either Cr-SRBC or Tc-sulphur colloid. Intravenous infusion of fat emulsions can cause RE blockade in animals.4 In man, intralipid can accumulate in Kupffer cellsand in the spleen;pigment accumulation in Kupffer cells is a characteristic finding after long-term infusions.7 But these present experiments have failed to show any evidence of RE blockade after large intravenous doses of intralipid. Similarly in man, RE blockade was not recorded after intralipid.’ Thus, there is no evidence to substantiate the fear that intralipid causes RE blockade. a
Department of Pathology, Medical School, Bristol B58 1TD
INTRALIPID AND RETICULOENDOTHELIAL BLOCKADE
SIR,—Dr Fischer and colleagues (Oct. 18, p.819) report that the pretreatment of mice with intraperitoneal (i.p.) ’Intralipid’ results in an increase in death rate and in bacteraemia after challenge with i.p. streptococci, and that these changes are associated with decreased neutrophil chemotaxis. However, they imply in the same paper that part of the diminution in bacterial defences caused by intralipid might be due to reticuloendothelial (RE) blockade. I here report experiments done to find out whether intralipid causes RE blockade in mice. ICR mice were injected intravenously with large doses of intralipid 10% (Cutter Laboratories). A volume of 0 - 5 ml in a mouse is equivalent, weight for weight, to 1 5 1 in a 70 kg man. After varying intervals, one of two labelled test particles was injected intravenously: 5 x 107 5’Cr-labelled sheep red blood cells (CrSRBC) were used to assess possible blockade of RE-dependent blood clearance as described previouslyl or 99mTc-sulphur colloid (’Tesuloid’, Squibb) was given in an equivalent dose to that used clinically because of reports that patients with hyperlipoproteinaemia show decreased hepatic RE uptake of this agent.2Other mice were pretreated with 500 mg dextran sulphate intravenously to cause RE blockade. Control mice were pretreated with 0. 5 ml saline. All groups were killed 2 h after receiving test labelled particles. The results are in the accompanying table. As expected, in control mice about 90% of the Cr-SRBCl or Tcsulphur colloidwas recovered from the liver, and less than 5% from the spleen. In dextran-sulphate-treated mice RE blockade resulted 1.
Bradfield JWB, Souhami RL, Addison IE. The mechanism of the adjuvant effect of
sulphate Immunology 1974; 26: 383-92. BA, Bardfield PA, Bodian JE, Sugarman LA, Hellman L. Liver scans in hyperlipoproteinemia. JAMA 1974; 227: 907-10. 3. Bradfield JWB, Wagner HN, Jr. The relative importance of blood flow and liver phagocytic function in the distribution of 99mTc-sulfur colloid.J Nucl Med 1977; dextran
SIR,—Fischer et al. gave ’Intralipid’ intraperitoneallyto mice for 3 days, followed by streptococci; more treated mice died than untreated controls. However, the suggestion that the mechanism for this increased mortality was a blockade of the RES by intralipid seems unjustified. Studies in man shown no such effect.’ Instead another mechanism appears not to have been controlled for. This is a physicochemically induced increased permeability of the peritoneal membrane for bacteria by the repeated instillations ofintralipid. As Dr Gordon (Nov. 8, p. 1021) has pointed out Fischer et al. give no details about the handling of the control animals-were they given repeated intraperitoneal injections of solvent or glucose (the latter would be interesting since the alternative to alimentation with fats is carbohydrates)? If the effect was on permeability the results seem irrelevant. An intraperitoneal injection of intra lipid isa strange route of administration in human medicine. In their next experiment Fischer et al. exposed human neutrophils in vitro to considerably higher concentrations of intralipid than those achieved in clinical practice, where the highest blood concentrations seem to be around 8 mg/ml when recommendations for infusions are followed.Lower doses of intralipid than 12 5 mg/ml should be tested to obtain information relevant to the Luzio NR, Blickens DA. Influence of intravenously administered lipids on reticuloendothelial function. J Reticuloendothel Soc 1966; 3: 250-70. 5. Du Toit DF, Villet WT, Heydenrych T. Fat emulsion deposition in mononuclear phagocyte system. Lancer 1978; ii 898. 6. Forbes GB. Splenic lipidosis after administration of intravenous fat emulsion J Clin Pathol 1978; 31: 765-71. 7. Thompson SW The pathology of parenteral nutrition with lipids Springfield. Illinois Charles C. Thomas, 1974. 121-217, 679-745, 801-62. 8. Jarstrand C, Bergham L, Lahnborg G. Human granolocyte and reticuloendothelial system function during Intralipid infusion J Parenteral Enteral Nutr 1978. 2:
4. Di
2. Sachs
18: 620.
J. W. B. BRADFIELD
663-70. 1. 2.
Jarstrand C, Berghem L, Lahnborg G Human granulocyte and reticuloendithelial system function during Intralipid infusion. J Parent Ent Nutr 1978, 2: 663-70 Hallberg D. Elimination of exogenous lipids from the blood stream. Acta Physiol Scand 1965; 65 suppl 254.
1139 EFFECT OF INTRALIPID ON THE BACTERICIDAL CAPACITY OF
NEUTROPHILS AND ON MIGRATION UNDER AGAROSE AFTER STIMULATION WITH EITHER SERUM OR AN E. COLI BACTERIAL FACTOR
Values as meantSE (n= 10). *% bacteria living after incubation for 45 or 90 min. tMigration (mm) stimulated by serum or E. coli bacterial factor.
aim of the study-i.e., to find out if intralipid hampers bacterial defences in man. Other studies have yielded such information, 1,3 and the dose of intra lipid seems critical. We have studied ten healthy volunteers given 500 ml of 10% intralipid over 6 h. Blood for determination of neutrophil bactericidal capacity and migration under agarose4 was obtained before infusion, at its end, and 2 h after the discontinuation. Neutrophil function was not affected in conditions chosen to adhere closely to those at clinical practice (see table). Further carefully controlled studies are needed to find out if intralipid really does impair host defence.
JAN PALMBLAD
Department of Medicine 4, Södersjukhuset, S-100 64 Stockholm, Sweden
OLLE BROSTRÖM ANN-MARI UDEN
Department of Clinical Bacteriology, Södersjukhuset, Stockholm
NIKOS VENIZELOS
Department of Experimental Surgery, Thoracic Clinic, Karolinska Hospital, Stockholm
SIR,-Patients who
are
GORDON LAHNBORG
candidates for total
determine the effect of the various nutrients on the immune system. Leucocyte chemotaxis is an important function of the phagocytic system and defective chemotaxis predisposes to infection and sepsis.5In agreement with the report from Dr Fischer and his colleagues we found that incubation with ’Intralipid’ of leucocytes from normals depressed chemotactic migration.6 During the intravenous administration of this fat emulsion to normal chemotaxis decreased in close correlation with the degree of hypertriglyceridaemia induced. However, chemotactic migration always returned to normal 22 h after the infusion was stopped. Earlier studies from our group had shown that the degree of hypertriglyceridaemia during intralipid infusion in patients, correlates with the impairment of leucocyte function, as measured by bactericidal capacity and nitroblue tetrazolium (NBT) reduction. Furthermore granulocytes from patients with type IV 8 hyperlipoproteinaemia show a decrease in NBT reduction. Fischer et al. found that bacterial clearance is impaired after the intraperitoneal injection of intralipid in mice. Our studies in patients showed that neither the phagocytic nor the catabolic function 3 Nordenström J, Jarstrand C, Wiernik A. Decreased chemotactic and random migration of leukocytes during Intralipid infusion. Am J Clin Nutr 1979; 32: 2416-22. 4. Afzelius BA, Ewetz L, Palmblad J, Udén AM, Venizelos N. Structure and function of neutrophils from patients with the immotile cilia syndrome. Acta Med Scand 1980;
145-54.
5. Editorial. Disorders of neutrophil function. Lancet 1974; i: 438. 6. Nordenström J, Jarstrand C, Wiernik A. Decreased chemotactic and random migration
of leukocytes during Intralipid infusion. Am J Clin Nutr 1979; 32: 2416-22. C, Berghem L, Lahnborg G. Human granulocyte and reticulo-endothelial system function during Intralipid infusion. J Parent Ent Nutr 1978; 2: 663-70. 8. Jarstrand C, Angelin B, Einarsson K. Decreased nitroblue tetrazolium reduction of granulocytes in type IV hyperlipoproteinemia. J Lab Clin Med 1979; 94: 897-901. 7. Jarstrand
Departments of Surgery and Clinical Bacteriology, Karolinska Institute, Huddinge Hospital, S-141 86 Huddinge, Sweden
JÖRGEN NORDENSTRÖM CONNIE JARSTRAND DAG HALLBERG
parenteral nutrition
(TPN) are prone to infection, and catheter sepsis is one of the most feared complications of intravenous feeding. Thus, in evaluating the nutritional support of patients in need of TPN it is important to
208:
of the reticuloendothelial system (125I-microaggregated human serum albumin method) was significantly affected by intralipid infusion.7 Indeed intralipid may enhance some immune functions. Our later studies have shown an increased NBT reduction in monocytes from patients receiving intralipid. In experiments with such cells in vitro, we have also noted an increased phagocytosis of fluorescein-labelled yeast particles, an increased chemotactic and random migration, and increased NBT reduction. The same changes were also found in alveolar macrophages from rabbits after incubation with intralipid in vitro (C. Jarstrand and A. Wiernik, unpublished). Others9 have shown that intralipid may also cause a significantly increased response of human thymic lymphocytes to mitogens and antigens in vitro. Patients who cannot meet their energy requirements orally are candidates for TPN, supplied as hypertonic glucose solutions and aminoacids ("glucose system") or with part of the carbohydrate calories substituted by intravenous fat emulsions ("lipid system"). Plasma triglyceride levels are higher for the glucose system than for the lipid system. 10 Since we found that the impairment of leucocyte function is correlated to the degree ofhypertriglyceridaemia, it may be that, despite the finding that intralipid per se diminishes antibacterial defence, the clinical alternative, in which a larger proportion of glucose has to be given, has an equal or more depressive effect on leucocyte function. Fischer et al., drawing on studies in mice and in vitro studies on neutrophils from volunteers, suggest that "Intralipid may enhance the risk of bacterial sepsis in certain patients". Our studies and Fischer’s are inconclusive in this respect, and we do not agree with your Oct. 18 editorial that the observations discussed strengthen the case against the use of fat emulsions in patients. Before any strong recommendation against the clinical use of intralipid is made, studies should be done on the alternative (i.e., administration of a larger proportion of carbohydrate calories).
HDL AND CORONARY HEART DISEASE
SIR,—Dr Key’s caution about the interpretation of data on high density lipoprotein (HDL) are well taken. It.is certainly undemonstrated that raising the concentration of HDL reduces the risk of coronary heart disease (CHD); and prophylaxis based on such a premise is, at the very least, premature. Moreover, as he points out, cross-cultural data are sparse and difficult to interpret. The role of HDL in populations with low levels of total cholesterol remains to be evaluated. Instead of considering HDL by itself, however, it might be more appropriate to use, for an estimation of CHD risk, either a linear combination of HDL and LDL (or total cholesterol) or a ratio of the two, as we have suggested.2 If LDL is atherogenic and HDL is counter-atherogenic, the balance between the two may be more relevant than either alone. This may be especially important for older persons or for groups with low concentrations of total blood cholesterol. The data Keys presents on non-CHD death are interesting, although they do not accord with our observations.3But it is not clear why long-term follow-up is preferable to short-term. When the entire cohort is dead, it follows that, if persons dying of CHD had a DM, Copeland EM, Corriere JN, Richie ER, Jacobson K, Dudrick SJ. The effect soybean oil emulsion on lymphocyte transformation. J Parent Ent Nutr 1978; 2: 112-15. 10. Broviac JW, Riella MC, Scribner BH. The role of Intralipid in prolonged parenteral nutrition I As a caloric substitute for glucose. AmJ Clin Nutr 1976; 29: 255-57 1. Keys A. Alpha lipoprotein (HDL) cholesterol in the serum and the risk of coronary heart disease and death Lancet 1980; ii: 603. 2. Gordon T, Castelli WP, Hjortalnd MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease: The Framingham study. Am J Med 1977; 62: 707. 3. Gordon T, Kannel WB, Castelli WP, Dawber TR. Lipoproteins, cardiovascular disease and death: The Framingham study. Arch Intern Med (in press). 9. Ota
ofa 10%