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HOT MONEY
383
NEUTROPHIL FUNCTION AND N.B.T. DYE REDUCTION
reported that in patients with bacterial SIR,-Park infections an increased proportion of neutrophils, when incubated with nitroblue-tetrazolium (N.B.T.) dye, sponet
al.l
this dye to form intracellular formazan deposits. A similar increase was not found in neutrophils from patients with viral infections or non-bacterial inflammatory disease. Subsequently false-positive reactions were reported in newborns and false-negative reactions in patients with2chronic granulomatous disease and lipochrome histiocytosis. It was suggested that the inappropriate N.B.T. reactions were associated with neutrophil dysfunction
taneously reduced
in these conditions. We report here another cause of false-positive reactions. Neutrophils from 5 subjects were studied 2-4 hours after intramuscular injection of 0-5 ml. of typhoid vaccine (U.S.P. Lilly, containing Salmonella typhi, S. paratyphi A, and S. paratyphi B). The in-vivo effects of the vaccine were thus evaluated without exposing cells to particulate matter or bacteria. As the accompanying table shows, the NEUTROPHILS
(%)
WITH SPONTANEOUS N.B.T. DYE REDUCTION
proportion of cells reducing N.B.T. measured by the method of Park et al.1 was significantly increased in all 5. Patient 5 was studied before and 2 hours after vaccination. The proportion of cells reducing N.B.T. increased from 7 to 40%. However, these " activated " neutrophils evinced no change in their intracellular bactericidal capacity, determined by the method of Alexander et awl.3 Furthermore, hexose-monophosphate-shunt activity, measured by 14CO2 production from glucose-1-14C,4 was not increased. Thus there was no evidence that these cells were hyperactive functionally or metabolically despite increased numbers of cells reducing N.B.T. This raises several questions concerning the significance of N.B.T. dye reduction and its relation to neutrophil function. Badmer and Nathan 56 suggested that dye reduction depended on NADH-oxidase stimulation after particle ingestion. Whether dye reduction depends on H202 production or subsequent stimulation of other 7-9 remains enzyme systems such as glutathione peroxidase uncertain. Also the relation of these enzymes to bactericidal function of the neutrophil is still undecided. The enzyme systems concerned with N.B.T. reduction are known to be associated with normal bactericidal ability. However, these same enzyme systems are present in normal amounts and are released normally 10 in patients with chronic granulomatous disease, in which neutrophil bactericidal function is 1. 2.
Park, B. H., Fikrig, S. M., Smithwick, E. M. Lancet, 1968, ii, 532. Park, B. H., Holmes, B. M.. Rodey, G. E., Good, R A. ibid. 1969, i, 157. 3. Alexander, J. W., Windhorst, B. B., Good, R. A. J. Lab. clin. Med. 1968, 72, 136. 4. 5. 6. 7. 8.
Sbarra, A. J., Karnovsky, M. L. J. biol. Chem. 1959, 234, 1355. Bæhnet, R. L., Nathan, D. G. Science, N.Y. 1967, 155, 835. Banner, R. L., Nathan, D. G. Blood, 1966, 28, 110. Bænner, R. L., Nathan, D. G. New Engl.J. Med. 1968, 278, 971. Holmes, B. M., Page, A. R., Good, R. A. J. clin. Invest. 1967, 46, 1422.
9.
Reed, P. W. J. biol. Chem. 1969, 244, 2459. 10. Bæhner, R. L., Karnovsky, M. J., Karnovsky, M. L. J. clin. Invest. 1968, 47, 187.
defective. Thompson et al.11 have described a family in which neutrophil bactericidal activity was deficient but N.B.T. dye reduction was normal in at least one family member. These observations, together with the results in a noninfected patient with Chediak-Higashi disease (see table) indicate that the actual presence of or contact with bacterial particulate matter is not necessary for stimulation of neutrophils to reduce N.B.T. spontaneously. Other conditions associated with increased lysosomal lability may have a similar effect. Until the mechanisms for N.B.T. reduction and its relation to neutrophil function in infectious disease are further elucidated, increased N.B.T. dye reduction as an index of bacterial infection should be regarded with caution. Children’s Hospital Research Foundation, OWEN C. GRUSH ALVIN M. MAUER. Cincinnati, Ohio 45229.
HOT MONEY the letter about the effect of metallic SIR,-Further inclusions in a microwave field (July 12, p. 106) we can now be more specific about the length of a metallic tissue implant which would concentrate the field sufficiently to burn the tissue. Our investigations indicate that the concentration of microwaves, around a length of metal embedded in a dielectric, waxes and wanes repeatedly as the length of the metal is increased. In general, the maximum concentrations occur with lengths of metal equal to even multiples of the quarter-wavelength of the microwaves in the dielectric. Similarly, the minimum concentrations occur with lengths equal to odd multiples of this quarter-wavelength. The smallest length producing maximum concentration is anomalous. It is equal to three-eighths of the wavelength in the dielectric, and produces the heaviest concentration of all the maximum concentration lengths. As this length is decreased, the concentration falls off rapidly. When the length is equal to or less than one-quarter of the wavelength in the dielectric, concentration is not detected. It should be noted that the wavelength in an unbounded dielectric is the free space wavelength divided by the square root of the relative permittivity of the dielectric. If these findings are applied to a tissue such as muscle to
(relative permittivity 50-60) one would expect the maximum safe length of a metallic implant to be 0-4 cm. where the free space wavelength of the microwaves is 12.5 cm. This would apply for all orientations of the implant. It is important to note that under these conditions the experimental findings predict the greatest possible concentration of the microwaves at an implant length of 0-6 cm. We stress the danger of using microwave diathermy in any tissue containing a metallic implant. Department of Surgery, Royal Infirmary, Manchester 13. Radio Techniques Laboratory, Electrical Engineering Department, U.M.I.S.T.
H. D. BAILLIE. A. G. HEATON D. K. PAL.
THE APPROACH TO HEROIN ADDICTION SIR,-I want to respond briefly to Dr. Griffith Edwards’ excellent papery and strongly to endorse its conclusions. Dr. Edwards states: " The purpose of this paper is to propose not that the British system is unworkable but something much to the contrary. A system which sees the addict as someone in need of help is totally to be preferred to one which treats him only as a criminal, and there need therefore be no embarrassment in admitting that the medically determined approach brings with it many difficulties." He then 11. Thompson, E. N., Cope, W. A., Chandra, R. K., Soothill, J. F. 12.
Lancet, 1969, i, 799. Edwards, G. ibid. p. 768.
NEUTROPHIL FUNCTION AND N.B.T. DYE REDUCTION
reported that in patients with bacterial SIR,-Park infections an increased proportion of neutrophils, when incubated with nitroblue-tetrazolium (N.B.T.) dye, sponet
al.l
this dye to form intracellular formazan deposits. A similar increase was not found in neutrophils from patients with viral infections or non-bacterial inflammatory disease. Subsequently false-positive reactions were reported in newborns and false-negative reactions in patients with2chronic granulomatous disease and lipochrome histiocytosis. It was suggested that the inappropriate N.B.T. reactions were associated with neutrophil dysfunction
taneously reduced
in these conditions. We report here another cause of false-positive reactions. Neutrophils from 5 subjects were studied 2-4 hours after intramuscular injection of 0-5 ml. of typhoid vaccine (U.S.P. Lilly, containing Salmonella typhi, S. paratyphi A, and S. paratyphi B). The in-vivo effects of the vaccine were thus evaluated without exposing cells to particulate matter or bacteria. As the accompanying table shows, the NEUTROPHILS
(%)
WITH SPONTANEOUS N.B.T. DYE REDUCTION
proportion of cells reducing N.B.T. measured by the method of Park et al.1 was significantly increased in all 5. Patient 5 was studied before and 2 hours after vaccination. The proportion of cells reducing N.B.T. increased from 7 to 40%. However, these " activated " neutrophils evinced no change in their intracellular bactericidal capacity, determined by the method of Alexander et awl.3 Furthermore, hexose-monophosphate-shunt activity, measured by 14CO2 production from glucose-1-14C,4 was not increased. Thus there was no evidence that these cells were hyperactive functionally or metabolically despite increased numbers of cells reducing N.B.T. This raises several questions concerning the significance of N.B.T. dye reduction and its relation to neutrophil function. Badmer and Nathan 56 suggested that dye reduction depended on NADH-oxidase stimulation after particle ingestion. Whether dye reduction depends on H202 production or subsequent stimulation of other 7-9 remains enzyme systems such as glutathione peroxidase uncertain. Also the relation of these enzymes to bactericidal function of the neutrophil is still undecided. The enzyme systems concerned with N.B.T. reduction are known to be associated with normal bactericidal ability. However, these same enzyme systems are present in normal amounts and are released normally 10 in patients with chronic granulomatous disease, in which neutrophil bactericidal function is 1. 2.
Park, B. H., Fikrig, S. M., Smithwick, E. M. Lancet, 1968, ii, 532. Park, B. H., Holmes, B. M.. Rodey, G. E., Good, R A. ibid. 1969, i, 157. 3. Alexander, J. W., Windhorst, B. B., Good, R. A. J. Lab. clin. Med. 1968, 72, 136. 4. 5. 6. 7. 8.
Sbarra, A. J., Karnovsky, M. L. J. biol. Chem. 1959, 234, 1355. Bæhnet, R. L., Nathan, D. G. Science, N.Y. 1967, 155, 835. Banner, R. L., Nathan, D. G. Blood, 1966, 28, 110. Bænner, R. L., Nathan, D. G. New Engl.J. Med. 1968, 278, 971. Holmes, B. M., Page, A. R., Good, R. A. J. clin. Invest. 1967, 46, 1422.
9.
Reed, P. W. J. biol. Chem. 1969, 244, 2459. 10. Bæhner, R. L., Karnovsky, M. J., Karnovsky, M. L. J. clin. Invest. 1968, 47, 187.
defective. Thompson et al.11 have described a family in which neutrophil bactericidal activity was deficient but N.B.T. dye reduction was normal in at least one family member. These observations, together with the results in a noninfected patient with Chediak-Higashi disease (see table) indicate that the actual presence of or contact with bacterial particulate matter is not necessary for stimulation of neutrophils to reduce N.B.T. spontaneously. Other conditions associated with increased lysosomal lability may have a similar effect. Until the mechanisms for N.B.T. reduction and its relation to neutrophil function in infectious disease are further elucidated, increased N.B.T. dye reduction as an index of bacterial infection should be regarded with caution. Children’s Hospital Research Foundation, OWEN C. GRUSH ALVIN M. MAUER. Cincinnati, Ohio 45229.
HOT MONEY the letter about the effect of metallic SIR,-Further inclusions in a microwave field (July 12, p. 106) we can now be more specific about the length of a metallic tissue implant which would concentrate the field sufficiently to burn the tissue. Our investigations indicate that the concentration of microwaves, around a length of metal embedded in a dielectric, waxes and wanes repeatedly as the length of the metal is increased. In general, the maximum concentrations occur with lengths of metal equal to even multiples of the quarter-wavelength of the microwaves in the dielectric. Similarly, the minimum concentrations occur with lengths equal to odd multiples of this quarter-wavelength. The smallest length producing maximum concentration is anomalous. It is equal to three-eighths of the wavelength in the dielectric, and produces the heaviest concentration of all the maximum concentration lengths. As this length is decreased, the concentration falls off rapidly. When the length is equal to or less than one-quarter of the wavelength in the dielectric, concentration is not detected. It should be noted that the wavelength in an unbounded dielectric is the free space wavelength divided by the square root of the relative permittivity of the dielectric. If these findings are applied to a tissue such as muscle to
(relative permittivity 50-60) one would expect the maximum safe length of a metallic implant to be 0-4 cm. where the free space wavelength of the microwaves is 12.5 cm. This would apply for all orientations of the implant. It is important to note that under these conditions the experimental findings predict the greatest possible concentration of the microwaves at an implant length of 0-6 cm. We stress the danger of using microwave diathermy in any tissue containing a metallic implant. Department of Surgery, Royal Infirmary, Manchester 13. Radio Techniques Laboratory, Electrical Engineering Department, U.M.I.S.T.
H. D. BAILLIE. A. G. HEATON D. K. PAL.
THE APPROACH TO HEROIN ADDICTION SIR,-I want to respond briefly to Dr. Griffith Edwards’ excellent papery and strongly to endorse its conclusions. Dr. Edwards states: " The purpose of this paper is to propose not that the British system is unworkable but something much to the contrary. A system which sees the addict as someone in need of help is totally to be preferred to one which treats him only as a criminal, and there need therefore be no embarrassment in admitting that the medically determined approach brings with it many difficulties." He then 11. Thompson, E. N., Cope, W. A., Chandra, R. K., Soothill, J. F. 12.
Lancet, 1969, i, 799. Edwards, G. ibid. p. 768.