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GARLIC
1426 did not alter this instability upon transfer to antibiotic-free The " revertants ", being sensitive, were medium. from the dwarf-colonies and were not derived evidently contaminants. The dwarf-colony and the " revertant " forms were catalase and coagulase positive, morphologically normal, sensitive to penicillin, tetracycline, and erythromycin, and belonged to phage type 81. The mechanism of the resistance of the clinical isolate was believed to be similar to that of the dwarf forms obtained in vitro. The latter probably possessed defective oxidative metabolism.1 The growth characteristics and resistance pattern of the clinical dwarf-colony and " revertant " forms were very similar when grown under anaerobic conditions (see table). It is well known that aerobic metabolism is required for uptake, and hence full activity, of aminoglucoside antibiotics.B Since these resistant dwarf-colony forms produce minute colonies after overnight incubation, they would be missed in the routine laboratory. Coexisting probably " revertants " would, because of their normal appearance, be preferentially tested for antibiotic sensitivity. Thus, wherever apparently sensitive staphylococci persist despite aminoglucoside therapy, these dwarf-colony forms should be suspected. Incubation for 72 hours will identify them by their highly pigmented and dome-shaped appearance, and by their size (about 1-2 mm. in diameter). We therefore propose that staphylococci (and possibly other organisms) can survive moderate levels of aminoglucoside antibiotics as a result of restrictions in their oxidative metabolism-a situation analogous to the withstanding of penicillin by L-forms. Departments of Bacteriology, University of Bristol and Law Hospital, R. W. LACEY Carluke, A. A. B. MITCHELL. Lanarkshire.
PREVENTION AND TREATMENT OF ALLERGIC REACTIONS SIR,-I was most interested in the report by Dr. Taub and his colleagues (Sept. 6, p. 521), which adds weight to some of my own findings. In 1963 I showed that very large doses of antigen do not produce sensitisation in man or in animals,9 and that similarly large doses can halt severe allergic reactions even after the onset of symptoms. For example, in serum sickness an injection of 100-200 ml. of antitetanus or antidiphtheria serum immediately abolished
I believe that certain reactions due sera, and drugs may be prevented, or
viruses, foreign treated, by giving large doses of antigen. This phenomenon could be of great importance to workers using foreign sera in immunosuppressive
to
treatment.
Agia Barbara Hospital, Athens, Greece.
L. KATSILABROS.
GARLIC interested in the letter by Dr. Srinivasan SIR,-I (Oct. 11, p. 800), suggesting that garlic may be useful in hypertension. Here in the U.S., Van Patten Pharmaceutical Company, 4450 Ravenswood Avenue, Chicago, Illinois, markets garlic tablets under the trade name ’Allimin’ for the treatment of hypertension. I used allimin tablets in a number of patients with hypertension in the early 1940s and found it totally ineffective. I would hardly call garlic a new antihypertensive agent. was
Summit, N.J. 07901.
F.
J. VINCI.
N.B.T. TESTS IN PREMATURE INFANTS SIR,-Park et al.1 have shown that a test based on the in-vitro reduction of nitroblue-tetrazolium (N.B.T.) dye by circulating neutrophils can be used to differentiate certain types of bacterial infection from non-bacterial diseases. In adult patients with bacterial infections the proportion of N.B.T.-positive leucocytes is higher than in patients with non-bacterial illnesses and in healthy controls. Although neutrophils from children with fatal granulomatosis give false-negative results, while false-positive results are obtained in newborn infants,2 the N.B.T. test remains a useful diagnostic aid. In order to assess further the effectiveness of the test, leucocytes from healthy premature infants, from premature infants known to have bacterial diseases, and from normal full-term infants were tested. The N.B.T. test was performed on 94 premature infants from 3 hours to 30 days old (weight range 1420-2150 g.), and also in 10 full-term infants from 1 to 18 days old (weight range 2950-4300 g.). The premature infants were TABLE I-RESULTS OF THE N.B.T. TEST IN FOUR GROUPS OF INFANTS
rash, fever, and glandular enlargement.lO I found that the same was true of allergic reactions to some drugs, especially penicillins and chloramphenicol. Thus, during an episode of penicillin allergy, injection of 5-20 million units of crystalline penicillin caused the reaction to subside.- I then extended the work to viruses, and found that when very large doses of virus (vaccinia, herpes, fixed Pasteur virus, &c.) were injected into guineapigs the animals did not become sick. 1 ml. of fixed Pasteur virus injected into guineapigs usually produced a fatal illness, but when 50 ml. was injected no illness was produced. I call this the
" apathy phenomenon ". With these results in mind, I tried the effect of injecting large amounts of homologous antigen into rabbits with skin-grafts. This prevented rejection reactions.12 In order to produce prolonged tolerance, even higher doses are needed-i.e., 100-200 ml. of equine serum daily for 5-10 days intramuscularly or subcutaneously. 8.
9. 10. 11. 12.
Kogut, M., Lightbrown, J. W., Isaacson, P. J. gen. Microbiol. 1965, 39, 155. Katsilabros, L. Revue med. Moy.-Orient. 1963, no. 6, 539. Katsilabros, L. ibid. no. 5, p. 468. Katsilabros, L. ibid. 1967, no. 4, 346. Katsilabros, L. Sixième Session des Journées Médicales du Proche Orient, Cairo, April, 1969.
divided into three groups: (I) 66 healthy babies; (II) 21 known to have bacterial diseases (skin abscesses, pneumonia, septicaemia, &c.); and (III) 7 with non-bacterial diseases. The fourth group consisted of 10 healthy full-term infants. The results of the N.B.T. tests in these four groups are shown in table i. N.B.T. tests were done periodically on 5 children in group 11, and the results of these are shown in table II. In the healthy premature infants and in the premature infants with non-bacterial illnesses the absolute number and the proportion of N.B.T.-positive neutrophils were increased. In 1. Park, B. H., Fikrig, S. M., Smithwick, E. M. Lancet, 1968, ii, 532. 2. Park, B. H., Holmes, B. M., Rodey, G. E., Good, R. A. ibid. 1969, i,
157.
PREVENTION AND TREATMENT OF ALLERGIC REACTIONS SIR,-I was most interested in the report by Dr. Taub and his colleagues (Sept. 6, p. 521), which adds weight to some of my own findings. In 1963 I showed that very large doses of antigen do not produce sensitisation in man or in animals,9 and that similarly large doses can halt severe allergic reactions even after the onset of symptoms. For example, in serum sickness an injection of 100-200 ml. of antitetanus or antidiphtheria serum immediately abolished
I believe that certain reactions due sera, and drugs may be prevented, or
viruses, foreign treated, by giving large doses of antigen. This phenomenon could be of great importance to workers using foreign sera in immunosuppressive
to
treatment.
Agia Barbara Hospital, Athens, Greece.
L. KATSILABROS.
GARLIC interested in the letter by Dr. Srinivasan SIR,-I (Oct. 11, p. 800), suggesting that garlic may be useful in hypertension. Here in the U.S., Van Patten Pharmaceutical Company, 4450 Ravenswood Avenue, Chicago, Illinois, markets garlic tablets under the trade name ’Allimin’ for the treatment of hypertension. I used allimin tablets in a number of patients with hypertension in the early 1940s and found it totally ineffective. I would hardly call garlic a new antihypertensive agent. was
Summit, N.J. 07901.
F.
J. VINCI.
N.B.T. TESTS IN PREMATURE INFANTS SIR,-Park et al.1 have shown that a test based on the in-vitro reduction of nitroblue-tetrazolium (N.B.T.) dye by circulating neutrophils can be used to differentiate certain types of bacterial infection from non-bacterial diseases. In adult patients with bacterial infections the proportion of N.B.T.-positive leucocytes is higher than in patients with non-bacterial illnesses and in healthy controls. Although neutrophils from children with fatal granulomatosis give false-negative results, while false-positive results are obtained in newborn infants,2 the N.B.T. test remains a useful diagnostic aid. In order to assess further the effectiveness of the test, leucocytes from healthy premature infants, from premature infants known to have bacterial diseases, and from normal full-term infants were tested. The N.B.T. test was performed on 94 premature infants from 3 hours to 30 days old (weight range 1420-2150 g.), and also in 10 full-term infants from 1 to 18 days old (weight range 2950-4300 g.). The premature infants were TABLE I-RESULTS OF THE N.B.T. TEST IN FOUR GROUPS OF INFANTS
rash, fever, and glandular enlargement.lO I found that the same was true of allergic reactions to some drugs, especially penicillins and chloramphenicol. Thus, during an episode of penicillin allergy, injection of 5-20 million units of crystalline penicillin caused the reaction to subside.- I then extended the work to viruses, and found that when very large doses of virus (vaccinia, herpes, fixed Pasteur virus, &c.) were injected into guineapigs the animals did not become sick. 1 ml. of fixed Pasteur virus injected into guineapigs usually produced a fatal illness, but when 50 ml. was injected no illness was produced. I call this the
" apathy phenomenon ". With these results in mind, I tried the effect of injecting large amounts of homologous antigen into rabbits with skin-grafts. This prevented rejection reactions.12 In order to produce prolonged tolerance, even higher doses are needed-i.e., 100-200 ml. of equine serum daily for 5-10 days intramuscularly or subcutaneously. 8.
9. 10. 11. 12.
Kogut, M., Lightbrown, J. W., Isaacson, P. J. gen. Microbiol. 1965, 39, 155. Katsilabros, L. Revue med. Moy.-Orient. 1963, no. 6, 539. Katsilabros, L. ibid. no. 5, p. 468. Katsilabros, L. ibid. 1967, no. 4, 346. Katsilabros, L. Sixième Session des Journées Médicales du Proche Orient, Cairo, April, 1969.
divided into three groups: (I) 66 healthy babies; (II) 21 known to have bacterial diseases (skin abscesses, pneumonia, septicaemia, &c.); and (III) 7 with non-bacterial diseases. The fourth group consisted of 10 healthy full-term infants. The results of the N.B.T. tests in these four groups are shown in table i. N.B.T. tests were done periodically on 5 children in group 11, and the results of these are shown in table II. In the healthy premature infants and in the premature infants with non-bacterial illnesses the absolute number and the proportion of N.B.T.-positive neutrophils were increased. In 1. Park, B. H., Fikrig, S. M., Smithwick, E. M. Lancet, 1968, ii, 532. 2. Park, B. H., Holmes, B. M., Rodey, G. E., Good, R. A. ibid. 1969, i,
157.