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EFFECTS OF PHYTOHÆMAGGLUTININ ON LEUCOCYTES
1012 in vitro ". This statement was correct, since the organism has not been cultured in vitro as yet. It does not imply that we assume that the human leprosy bacillus will never be cultured, and is inconsistent with a part of our published work carried out at the National Institute for Medical Research, where for the past ten years we have been studying the tissue-culture conditions and conditions in cell-free media for the cultivation and growth of both rat and human leprosy bacilli. Finally, Dr. Corcos refers to a hypothesis, which he has presentedthat the " dichotomy in leprosy " (namely, the polar types of tuberculoid and lepromatous leprosy) may arise, not from different responses of the host to the human leprosy bacillus, but from the response of the host to two genetically separate pathogens-one of which is a mycobacterium, the other its contained parasite. This suggestion is at present entirely hypothetical, since the human leprosy bacillus has not been cultured in vitro. If his hypothesis is correct, it would be unique to leprosy, since this kind of response has not been observed in any other bacterial infection. In leprosy it is very easy (and often tempting) to adumbrate unusual hypotheses, because hitherto these could not be tested experimentally. Now, fortunately, the successful transmission of leprosy in the mouse foot-pad provides an experimental approach for studying the pathogenesis of leprosy.
Recent experimental results indicate that bacilli coming from lepromatous patients and patients with borderline or near-tuberculoid type infections produce an identical type of infection in the mouse foot-pad, which would be most unlikely if Dr. Corcos’ explanation of " dichotomy were relevant. National Institute for Medical
Research,
R.
Mili Hill, London, N.W.7.
J. W. REES.
TOXIC EFFECTS OF STEROIDS
SIR,-Dr. Kelly (Oct. 24) disapproves of the administration of steroids in herpes zoster on the ground that the " alleged risks are unjustified in a self-limited virus disease ". While it is true that the acute infection is selflimited,post-herpetic neuralgia may last months or years; and it is this very common sequel which we are trying to prevent-thus far with complete success in over 40 patients-a result which is in agreement with the results in a very much larger series of herpes ophthalmicus treated by Dr. Harold Scheie, who was quoted in my paper. Philadelphia, Pennsylvania, U.S.A.
FRANK RANK LLIOTT. ELLIOTT.
EFFECTS OF PHYTOHÆMAGGLUTININ ON LEUCOCYTES short reference SIR,-Our 12) to the phyto(Sept. " " effect a as primary reaction in hxmagglutinin (P.H.A.) connection with the finding that foetal lyrnphocytes respond to P.H.A. may have caused Mr. Coulson and Dr. Chalmers (Oct. 10) to misunderstand our ideas about the action of P.H.A. not think that the effect of P.H.A. is simply a result of antigenic properties. Nevertheless, no preimmunisation seems to be necessary, and consequently, if the P.H.A. reaction is analogous to antigenic stimulation, the cells would react as in a primary response or in a first-set homograft or a graftversus-host reaction. One of us has suggested: Suppose that P.H.A. makes a short cut when it triggers off the mitotic cycle, that is to say comes in later than an antigen does in the chain of events leading to antibody production and/or mitosis and, therefore, circumvents the claims for specificity and other antigenic properties."11 Our present view is (1) that P.H.A. stimulation is not
We do
its
"
necessarily limited 7. 8.
to
"
committed
"
lymphocytes and, in
Corcos, M. G. Leprosy Rev. 1964, 35, 61. Lindahl-Kiessling, K. XIth International Congress of Genetics, p. 300. 1963.
particular, not to specifically preimmunised cell clones 9; and (2) that the cell response to P.H.A. may nevertheless be immunological. K. LINDAHL-KIESSLING J. A. BÖÖK.
Institute for Medical Genetics, University of Uppsala,
Sweden.
WHY DON’T WE TELL? SIR,-It may be your privilege, if not your duty, to castigate your colleagues in what you take to be the public interest, but it is unworthy to misrepresent their motives. Surely no-one has suggested that to publish news of the unfortunate events at the Birmingham Eye Hospital would " run madly in the streets, faint in public cause people to
places, or pine through fear in privacy "; but it would certainly be likely to arouse unreasonable apprehension in many undergoing ophthalmic operations, would probably deter the timorous from seeking necessary treatment, and might well cause genuine alarm to those about to enter hospital. Could it be in the interest of other patients or the general public to see the poor old lady on the television broadcasting that had she known what might befall, she would never have consented to be treated ? Publication of such personal disasters is in the public interest only if this is necessary to ensure adequate investigation or to safeguard others. But there is no suggestion that the staff of Birmingham Eye Hospital had not already taken all the necessary steps to ascertain the source of the infection and precautions to prevent it. Are they to be censured because their secretary replied with literal truth to ill-informed inquiries on the telephone ? Would it really benefit or help the general public and our patients if all mishaps in hospitals were noted in the papers ? No, Sir. Many who care for patients would not accept the strictures in your leader of Oct. 10. CHRISTOPHER HEATH. Falmouth. CIRCULATING GASTRIC SECRETOGOGUE IN ZOLLINGER-ELLISON SYNDROME SIR,-Dr. Sircus is to be congratulated on the demonstration of a gastric secretogogue in the circulation and gastric juice of 2 patients with the Zollinger-Ellison
syndrome (Sept. 26). We recently submitted for publication a case-report of a Bantu female with the Zollinger-Ellison syndrome in whom a long clinical remission and achlorhydria were induced by means of radiotherapy to the gastric remnant. An emergency hemigastrectomy had previously been carried out for a bleeding duodenal ulcer and recurrent jejunal ulceration had developed two weeks after operation. The patient’s basal acid secretion after gastrectomy was 24-5 mEq. per hour and the maximum acid output was 24-1mEq. per hour. This patient’s serum was shown to contain a gastric secretogogue which produced a volume and acid response in a trained Heidenhain-pouch preparation. The dog, achlorhydric under basal conditions, showed an acid secretory response similar to that reported by Dr. Sircus and to the response obtained after the injection of gastrin extracts from ulcerogenic tumour tissue. 2 patients with duodenal ulceration associated with basal hypersecretion were selected as controls. The dog remained achlorhydric for three hours after injection of the same amount of serum obtained from the patient with the Zollinger-Ellison
syndrome. Our findings differ
from those reported by Dr. demonstrate acid stimulation without the prior administration of histamine to the dog. Dr. Sircus did not indicate whether an acid-secretory response could be obtained by injecting serum into a dog under otherwise basal conditions. In this regard it may be important that we used a large volume (30-50 ml.) of serum concentrated down,to a volume of 5 ml. by pervaporation at 37°C before
Sircus, in that
9.
slightly
we were
al3le
to
Speirs, R. S. Ann. N.Y. Acad. Sci. 1964, 113,
injection.
819.
Recent experimental results indicate that bacilli coming from lepromatous patients and patients with borderline or near-tuberculoid type infections produce an identical type of infection in the mouse foot-pad, which would be most unlikely if Dr. Corcos’ explanation of " dichotomy were relevant. National Institute for Medical
Research,
R.
Mili Hill, London, N.W.7.
J. W. REES.
TOXIC EFFECTS OF STEROIDS
SIR,-Dr. Kelly (Oct. 24) disapproves of the administration of steroids in herpes zoster on the ground that the " alleged risks are unjustified in a self-limited virus disease ". While it is true that the acute infection is selflimited,post-herpetic neuralgia may last months or years; and it is this very common sequel which we are trying to prevent-thus far with complete success in over 40 patients-a result which is in agreement with the results in a very much larger series of herpes ophthalmicus treated by Dr. Harold Scheie, who was quoted in my paper. Philadelphia, Pennsylvania, U.S.A.
FRANK RANK LLIOTT. ELLIOTT.
EFFECTS OF PHYTOHÆMAGGLUTININ ON LEUCOCYTES short reference SIR,-Our 12) to the phyto(Sept. " " effect a as primary reaction in hxmagglutinin (P.H.A.) connection with the finding that foetal lyrnphocytes respond to P.H.A. may have caused Mr. Coulson and Dr. Chalmers (Oct. 10) to misunderstand our ideas about the action of P.H.A. not think that the effect of P.H.A. is simply a result of antigenic properties. Nevertheless, no preimmunisation seems to be necessary, and consequently, if the P.H.A. reaction is analogous to antigenic stimulation, the cells would react as in a primary response or in a first-set homograft or a graftversus-host reaction. One of us has suggested: Suppose that P.H.A. makes a short cut when it triggers off the mitotic cycle, that is to say comes in later than an antigen does in the chain of events leading to antibody production and/or mitosis and, therefore, circumvents the claims for specificity and other antigenic properties."11 Our present view is (1) that P.H.A. stimulation is not
We do
its
"
necessarily limited 7. 8.
to
"
committed
"
lymphocytes and, in
Corcos, M. G. Leprosy Rev. 1964, 35, 61. Lindahl-Kiessling, K. XIth International Congress of Genetics, p. 300. 1963.
particular, not to specifically preimmunised cell clones 9; and (2) that the cell response to P.H.A. may nevertheless be immunological. K. LINDAHL-KIESSLING J. A. BÖÖK.
Institute for Medical Genetics, University of Uppsala,
Sweden.
WHY DON’T WE TELL? SIR,-It may be your privilege, if not your duty, to castigate your colleagues in what you take to be the public interest, but it is unworthy to misrepresent their motives. Surely no-one has suggested that to publish news of the unfortunate events at the Birmingham Eye Hospital would " run madly in the streets, faint in public cause people to
places, or pine through fear in privacy "; but it would certainly be likely to arouse unreasonable apprehension in many undergoing ophthalmic operations, would probably deter the timorous from seeking necessary treatment, and might well cause genuine alarm to those about to enter hospital. Could it be in the interest of other patients or the general public to see the poor old lady on the television broadcasting that had she known what might befall, she would never have consented to be treated ? Publication of such personal disasters is in the public interest only if this is necessary to ensure adequate investigation or to safeguard others. But there is no suggestion that the staff of Birmingham Eye Hospital had not already taken all the necessary steps to ascertain the source of the infection and precautions to prevent it. Are they to be censured because their secretary replied with literal truth to ill-informed inquiries on the telephone ? Would it really benefit or help the general public and our patients if all mishaps in hospitals were noted in the papers ? No, Sir. Many who care for patients would not accept the strictures in your leader of Oct. 10. CHRISTOPHER HEATH. Falmouth. CIRCULATING GASTRIC SECRETOGOGUE IN ZOLLINGER-ELLISON SYNDROME SIR,-Dr. Sircus is to be congratulated on the demonstration of a gastric secretogogue in the circulation and gastric juice of 2 patients with the Zollinger-Ellison
syndrome (Sept. 26). We recently submitted for publication a case-report of a Bantu female with the Zollinger-Ellison syndrome in whom a long clinical remission and achlorhydria were induced by means of radiotherapy to the gastric remnant. An emergency hemigastrectomy had previously been carried out for a bleeding duodenal ulcer and recurrent jejunal ulceration had developed two weeks after operation. The patient’s basal acid secretion after gastrectomy was 24-5 mEq. per hour and the maximum acid output was 24-1mEq. per hour. This patient’s serum was shown to contain a gastric secretogogue which produced a volume and acid response in a trained Heidenhain-pouch preparation. The dog, achlorhydric under basal conditions, showed an acid secretory response similar to that reported by Dr. Sircus and to the response obtained after the injection of gastrin extracts from ulcerogenic tumour tissue. 2 patients with duodenal ulceration associated with basal hypersecretion were selected as controls. The dog remained achlorhydric for three hours after injection of the same amount of serum obtained from the patient with the Zollinger-Ellison
syndrome. Our findings differ
from those reported by Dr. demonstrate acid stimulation without the prior administration of histamine to the dog. Dr. Sircus did not indicate whether an acid-secretory response could be obtained by injecting serum into a dog under otherwise basal conditions. In this regard it may be important that we used a large volume (30-50 ml.) of serum concentrated down,to a volume of 5 ml. by pervaporation at 37°C before
Sircus, in that
9.
slightly
we were
al3le
to
Speirs, R. S. Ann. N.Y. Acad. Sci. 1964, 113,
injection.
819.