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FAT-EMULSION DEPOSITION IN MONONUCLEAR PHAGOCYTIC SYSTEM
898 SERUM
&bgr;2-MICROGLOBULlN IN LYMPHOMA
We agree with Amlot and Adinolfi that chemotherapy can confuse the picture. Analysis of samples taken on day 1, 8, and 29 of M.O.P.P., C.H.O.P., and c.o.p. chemotherapy schedules in lymphoma have indicated that the serum-&bgr;-M.G. usually undergoes repeated cyclic depression, evident on the 8th day and disappearing by the time the next course begins on day 29. This is not evident in the less aggressively treated C.L.L. Unit for Cancer Research, University of Leeds, Leeds LS2 9NL
B. SPATI E. H. COOPER
Department of Hæmatology, General Infirmary Leeds
J. A. CHILD
FAT-EMULSION DEPOSITION IN MONONUCLEAR PHAGOCYTIC SYSTEM
SIR,-’Intralipid,’ a derivative of soya-bean oil, is widely used in long-term fat emulsion for total parenteral nutrition. Febrile reactions, disturbed liver function, coagulopathy, widespread lipidosis, and displacement of bilirubin from albumin have been reported after its use.’ Intralipid particles are phagocytosed by the mononuclear phagocytic system (M.p.s.).’ Long-term usage in dogs has been followed by intravenous fat pigmentation in the liver, lung, and spleen associated with a proliferation of reticuloendothelial cells containing lipid in the liver.’ The hepatic parenchyma contained microgranulomas composed of small aggregates of lipid-laden epithelial cells. Electronmicroscopy showed fat pigment deposited in the lysosomes, mitochondrial swelling, central core formation, and dilatation of profiles of rough endoplasmic reticulum with dislocation ofribosomes.’ The accumulation of fat particles in the M.P.S. occurs in man and in laboratory animals. In the liver the lipid is transported into the spaces of Disse before being taken up by the Kupffer cells.’ When the M.p.s. is blocked by fat, antibody production may be reduced which could result in increased susceptibility to sepsis.l Overloading the M.p.s. in rabbits with carbon and colloidal iron has resulted in a dramatic inhibition of the primary and secondary response.2 This susceptibility to infection must be carefully considered because patients who receive fat emulsions are usually very ill and in a catabolic phase with a negative nitrogen balance, and they are also likely to have defective immune functions. We have seen a case where lipid particles were taken up into the Kupffer cells in the liver. Intralipid and a synthetic aminoacid solution were infused into a 3-year-old patient for 4 weeks, after a corrosive injury to the oesophagus. A gastrostomy tube was inserted, and at laparotomy a liver biopsy was taken because the macroscopic appearance suggested fatty infiltration. Light microscopy on sections stained with oil-red 0 showed swollen Kupffer cells indicating striking lipid uptake. Cloudy swelling with occasional vacuole formation was noted in the hepatocytes. Conformational changes of cell injury were 1.
Johnston,
I. D. A.
(editor) Advances
1978. 2.
Cruchaud, A. Lab. Invest. 1968, 19, 1.
in Parenteral Nutrition, Lancaster,
Kupffer cell containing lipid vacuoles in cytoplasm. N=nucleus; ER=granular endoplasmic reticulum; (xI5000).
L=lipid
apparent on electronmicroscopy. The hepatocytes showed dilatation of rough endoplasmic reticulum and dislocation of ribosomes; occasional mitochondria of the lamellar type were swollen; scattered liposomes were noted in the vascular and canalicular poles of the hepatocytes. Microbodies were sparse. The endothelial cells and particularly the Kupffer cells were heavily laden with liposomes (see figure). Fat-emulsion particles accumulate in the M.p.s., and the mild anaemia, thrombocytopenia, and changes in liver function described with long-term use of fat emulsions, may all relate to the M.p.s. involvement. These observations call for morecaution with the use of fat emulsions.
slight
Tygerberg Hospital, Parow Valley, Cape, South Africa
D. F. DU TOIT W. T. VILLET J. HEYDENRYCH
THEOPHYLLINE PHARMACOKINETICS AND RESPIRATORY INFECTIONS
SIR,-We can support the finding by Chang et a1.1 that acute virus infections may alter theophylline pharmacokinetics. Over a 3-month period we assessed theophylline disposition on four occasions in a male aged 32 years who was in good general health and was not taking medication. We gave an intravenous infusion of aminophylline followed by serial measurements of serum-theophylline concentrations hourly for 8 h. During one of these investigations the volunteer suffered a mild upper respiratory infection characterised by coryza, sore throat, and fever. The serum theophylline half-life (t2 ) was 12-9h, body clearance 32-8ml/kg/h, and apparent volume of distribution (V) 0.61 1/kg. In the other three studies tzwas 6.4±1-4 h, clearance 82.8±13-4 ml/kg/h, and
respiratory
VO.74
±0.011
1/kg.
In ten healthy volunteers we found (unpublished) that theophylline tvaried by an average of 1-88 h within a period of 4 days; so, before viral illnesses are implicated as causing decreased theophylline clearance, larger numbers of patients should be studied and other variables affecting theophylline
metabolism, such as diet,2 should be controlled. JOHN A. FLEETHAM Departments of Medicine and Pharmacology, KANJI NAKATSU Queen’s University, PETER W. MUNT
Kingston, Ontario, Canada 1. 2.
Chang, K. C., Bell, T. D., Lauer, B. A., Choi, H. Lancet, 1978, i, 1132. Kappas, A., Anderson, Ther. 1976, 20, 643.
K.
E., Conney, A. H., Alvares, A. P. Clin. Pharmac.
&bgr;2-MICROGLOBULlN IN LYMPHOMA
We agree with Amlot and Adinolfi that chemotherapy can confuse the picture. Analysis of samples taken on day 1, 8, and 29 of M.O.P.P., C.H.O.P., and c.o.p. chemotherapy schedules in lymphoma have indicated that the serum-&bgr;-M.G. usually undergoes repeated cyclic depression, evident on the 8th day and disappearing by the time the next course begins on day 29. This is not evident in the less aggressively treated C.L.L. Unit for Cancer Research, University of Leeds, Leeds LS2 9NL
B. SPATI E. H. COOPER
Department of Hæmatology, General Infirmary Leeds
J. A. CHILD
FAT-EMULSION DEPOSITION IN MONONUCLEAR PHAGOCYTIC SYSTEM
SIR,-’Intralipid,’ a derivative of soya-bean oil, is widely used in long-term fat emulsion for total parenteral nutrition. Febrile reactions, disturbed liver function, coagulopathy, widespread lipidosis, and displacement of bilirubin from albumin have been reported after its use.’ Intralipid particles are phagocytosed by the mononuclear phagocytic system (M.p.s.).’ Long-term usage in dogs has been followed by intravenous fat pigmentation in the liver, lung, and spleen associated with a proliferation of reticuloendothelial cells containing lipid in the liver.’ The hepatic parenchyma contained microgranulomas composed of small aggregates of lipid-laden epithelial cells. Electronmicroscopy showed fat pigment deposited in the lysosomes, mitochondrial swelling, central core formation, and dilatation of profiles of rough endoplasmic reticulum with dislocation ofribosomes.’ The accumulation of fat particles in the M.P.S. occurs in man and in laboratory animals. In the liver the lipid is transported into the spaces of Disse before being taken up by the Kupffer cells.’ When the M.p.s. is blocked by fat, antibody production may be reduced which could result in increased susceptibility to sepsis.l Overloading the M.p.s. in rabbits with carbon and colloidal iron has resulted in a dramatic inhibition of the primary and secondary response.2 This susceptibility to infection must be carefully considered because patients who receive fat emulsions are usually very ill and in a catabolic phase with a negative nitrogen balance, and they are also likely to have defective immune functions. We have seen a case where lipid particles were taken up into the Kupffer cells in the liver. Intralipid and a synthetic aminoacid solution were infused into a 3-year-old patient for 4 weeks, after a corrosive injury to the oesophagus. A gastrostomy tube was inserted, and at laparotomy a liver biopsy was taken because the macroscopic appearance suggested fatty infiltration. Light microscopy on sections stained with oil-red 0 showed swollen Kupffer cells indicating striking lipid uptake. Cloudy swelling with occasional vacuole formation was noted in the hepatocytes. Conformational changes of cell injury were 1.
Johnston,
I. D. A.
(editor) Advances
1978. 2.
Cruchaud, A. Lab. Invest. 1968, 19, 1.
in Parenteral Nutrition, Lancaster,
Kupffer cell containing lipid vacuoles in cytoplasm. N=nucleus; ER=granular endoplasmic reticulum; (xI5000).
L=lipid
apparent on electronmicroscopy. The hepatocytes showed dilatation of rough endoplasmic reticulum and dislocation of ribosomes; occasional mitochondria of the lamellar type were swollen; scattered liposomes were noted in the vascular and canalicular poles of the hepatocytes. Microbodies were sparse. The endothelial cells and particularly the Kupffer cells were heavily laden with liposomes (see figure). Fat-emulsion particles accumulate in the M.p.s., and the mild anaemia, thrombocytopenia, and changes in liver function described with long-term use of fat emulsions, may all relate to the M.p.s. involvement. These observations call for morecaution with the use of fat emulsions.
slight
Tygerberg Hospital, Parow Valley, Cape, South Africa
D. F. DU TOIT W. T. VILLET J. HEYDENRYCH
THEOPHYLLINE PHARMACOKINETICS AND RESPIRATORY INFECTIONS
SIR,-We can support the finding by Chang et a1.1 that acute virus infections may alter theophylline pharmacokinetics. Over a 3-month period we assessed theophylline disposition on four occasions in a male aged 32 years who was in good general health and was not taking medication. We gave an intravenous infusion of aminophylline followed by serial measurements of serum-theophylline concentrations hourly for 8 h. During one of these investigations the volunteer suffered a mild upper respiratory infection characterised by coryza, sore throat, and fever. The serum theophylline half-life (t2 ) was 12-9h, body clearance 32-8ml/kg/h, and apparent volume of distribution (V) 0.61 1/kg. In the other three studies tzwas 6.4±1-4 h, clearance 82.8±13-4 ml/kg/h, and
respiratory
VO.74
±0.011
1/kg.
In ten healthy volunteers we found (unpublished) that theophylline tvaried by an average of 1-88 h within a period of 4 days; so, before viral illnesses are implicated as causing decreased theophylline clearance, larger numbers of patients should be studied and other variables affecting theophylline
metabolism, such as diet,2 should be controlled. JOHN A. FLEETHAM Departments of Medicine and Pharmacology, KANJI NAKATSU Queen’s University, PETER W. MUNT
Kingston, Ontario, Canada 1. 2.
Chang, K. C., Bell, T. D., Lauer, B. A., Choi, H. Lancet, 1978, i, 1132. Kappas, A., Anderson, Ther. 1976, 20, 643.
K.
E., Conney, A. H., Alvares, A. P. Clin. Pharmac.