1206
ple screening method for chronic granulomatous disease (C.G.D.). As granulomas are a constant finding in c.G.n., the absence of which was discussed, a note on biopsy findings in the case-reports might have been of value. The reported standard deviation in the intracellular killing after 120 minutes is surprisingly small (3-2%, mean 90-4), in a system with living neutrophils and bacteria. The significance must be interpreted with caution especially if the tabulated value of 79.2% is the correct one for case 2 and not the point placed at 75% in fig. 2. Also the analyses were performed only once in each case one year apart, and patient 2 was probably on steroid therapy. Do the authors believe that the stated microbicidal defect explains the clinical pictures in their cases?
BÖRJE ELGEFORS RAGNAR HULTBORN SANTE OLLING HANS PETERSON
Department of Infectious Diseases, University of Göteborg, S-416 85
Göteborg,
Sweden.
NEW FAMILIAL DEFECT IN MICROBICIDAL FUNCTION OF POLYMORPHONUCLEAR
LEUCOCYTES
SIR,-Dr van der Meer and his colleagues (Oct. 4, p. 630) describe a family with defective polymorphonuclear leucocyte function which meets the current description of chronic granulomatous disease (C.G.D.). C.G.D. has been defined as a syndrome of recurrent purulent infections, most commonly of the skin, subcutaneous tissues, and reticuloendothelial organs. This syndrome is associated with a particular defect of phagocytic function: the patient’s cells can ingest bacteria and fungi normally but cannot kill catalase-positive organisms that do not
effectively produce hydrogen peroxide.’ Dr van der Meer’s paper accords with two reports of C.G.D. in male and female siblings.23 The metabolic studies in family are typical of the oxidative defects of their C.G.D. It may be that their patients and others with autosomal recessive inheritance of the syndrome have a different basic enzymatic defect than those with X-linked disease, but until the specific biochemical defects can be accurately defined, there is no justification for calling this phagocytic defect a new one. Duke
University Medical Center,
Durham, North Carolina 27710, and
University of Alabama, Birmingham, Alabama, U.S.A.
CATHERINE M. WILFERT RICHARD B. JOHNSTON, JR.
RABIES
SIR,-It would be a great help to doctors if holidaymakers, before going abroad, were to learn not to befriend any animal whatsoever. If they do get bitten by a domestic animal such as a dog, the name and address of the owner should be taken, the vaccination status of the animal should be ascertained, and local medical assistance should be sought. Though it is true that duck-embryo vaccine (D.E.v.) has achieved popularity in the U.S.A. and in the U.K. because it is freer from neuroparalytic incidents which follow the older c.N.s. tissue vaccines, doubts have been cast on its efficacy. It is therefore time to produce and evaluate the newer and more powerful (and more expensive) tissue-culture vaccines and subunit vaccines because two or three doses of these vaccines effect the same rise of serum neutralising antibodies as does a full course Of D.E.V. Modern laboratory diagnostic methods have speeded up considerably the diagnosis of rabies, and in many cases there is no need to wait until the suspect animal exhibits signs and sympBellanti, J. A., Dayton, D. H. (editors) The Phagocytic Cell in Host Resistance; p. 225. New York, 1975. 2. Johnston, R. B., Jr., Wilfert, C. M., Buckley, R. H., Webb, L. S. DeChatelet, C. R., McCall, E. D. Lancet, 1975, i, 824. 3. Malawista, S. E., Gifford, R. H. Clin. Res. 1975, 23, 416a. 1.
dies from the disease; also there are diagnostic tests be done on the live animal and may prove positive three days before clinical signs develop in the suspect
toms or
which
can
two or
animal.
Royal Army
Medical
College,
Millbank, London SW1P 4RJ.
ETHELWALD E. VELLA
RADIATION AND PITUITARY FUNCTION IN CHILDREN
StR,—We read with great interest the article by Shalet and others.’ Some of our data on the effect of extracranial irradiation on pituitary function in children are pertinent. 23 They
supplement and even clarify certain points, since our study to only one of the factors in Shalet et al.’s report-namely, radiation. Furthermore, radiation in our group was administered in the absence of recognisable intracranial disease. In addition, our study is prospective and, in the planning, certain questions, such as effects of corticoids or other drugs, 4
refers
taken into account.4 secretion of growth hormone (G.H.) was studied in leukaemic children before and immediately after 18 days of "prophylactic" cranial irradiation. Plasma-G.H. was determined by radioimmunoassay in samples obtained hourly from 8 P.M. to7 A.M. during natural sleep. Cortisone had been discontinued 30-60 days before irradiation, and during irradiation mercaptopurine was given in half the dose used before. Plasma-G.H. values before irradiation were similar to those in normal children, a finding strongly suggesting normal pituitary function before irradiation. Immediately after the end of irradiation, and only 18 days after the first sampling, plasma-G.H. levels were very low. Group A in the report by Shalet et al. was studied 3 months after neurosurgery and, as it seems, 2 weeks after the start of cranial irradiation. Shalet et al. tend to attribute G.H. suppression in group A to the neurosurgical operation and they feel it is unlikely to have been caused by the irradiation, because of the short interval in time. Our data, however, favour such a hypothesis, since suppression of pituitary function was seen quite early. Follow-up of our group, thus far, indicates recovery of pituitary function 6-12 months later, while in Shalet et al.’s report no improvement in pituitary function with time was demonstrated. Two explanations may be offered: (1) with smaller doses of irradiation recovery of function is possible, while with higher doses the damage is permanent in some cases (our children received 2400 rads from a 60CO source; although the radiation dose is not given in Shalet et al.’s data, it must be much higher); (2) the radiation is an unrelated or only a contributing factor and the primary cause of pituitary insufficiency is surgery, as your contributors suggested. The first explanation seems more likely. One may wonder why, for so many years, the healthy pituitary has been considered resistant to conventional irradiation, in the doses usually applied for intracranial disease. The data, so far, even the biochemical data, did not include measurements of G.H., and the most important observations were made in adults. It is tempting to speculate that the pituitary may be more vulnerable to irradiation during the years of active growth, and much more so as far as G.H. and gonadotrophins are concerned. Support for this hypothesis probably emerges from the growth data in atomic-bomb victims.’ It is obvious that more
were
Spontaneous night
1.
Shalet, S. M., Beardwell, C. G., Morrisjone, P. H., Pearson, D. Lancet, July
19, 1975, p. 104. Dacou-Voutetakis, C., Xypolyta, A., Haidas, St., Constantinidis, M., Zannos-Mariolea, L. 13th annual meeting, European Society of Pediatric Endocrinology, Paris, Sept. 12-15, 1974; p. 38. 3. Dacou-Voutetakis, C., Xypolyta, A., Haidas, St., Constantinidis, M., Zannos-Mariolea, L. Ped. Res. 1975, 9, 686. 4. Dacou-Voutetakis, C., Xypolyta, A., Haidas, St., Constantinidis, M., Papavasiliou, C., Zannos-Mariolea, L. J. clin. Endocr. Metab. (in the press). 5. Sutow, W. W., Conard, R. A., Griffith, R. M. Pediatrics, 1965, 36, 721. 2.
ple screening method for chronic granulomatous disease (C.G.D.). As granulomas are a constant finding in c.G.n., the absence of which was discussed, a note on biopsy findings in the case-reports might have been of value. The reported standard deviation in the intracellular killing after 120 minutes is surprisingly small (3-2%, mean 90-4), in a system with living neutrophils and bacteria. The significance must be interpreted with caution especially if the tabulated value of 79.2% is the correct one for case 2 and not the point placed at 75% in fig. 2. Also the analyses were performed only once in each case one year apart, and patient 2 was probably on steroid therapy. Do the authors believe that the stated microbicidal defect explains the clinical pictures in their cases?
BÖRJE ELGEFORS RAGNAR HULTBORN SANTE OLLING HANS PETERSON
Department of Infectious Diseases, University of Göteborg, S-416 85
Göteborg,
Sweden.
NEW FAMILIAL DEFECT IN MICROBICIDAL FUNCTION OF POLYMORPHONUCLEAR
LEUCOCYTES
SIR,-Dr van der Meer and his colleagues (Oct. 4, p. 630) describe a family with defective polymorphonuclear leucocyte function which meets the current description of chronic granulomatous disease (C.G.D.). C.G.D. has been defined as a syndrome of recurrent purulent infections, most commonly of the skin, subcutaneous tissues, and reticuloendothelial organs. This syndrome is associated with a particular defect of phagocytic function: the patient’s cells can ingest bacteria and fungi normally but cannot kill catalase-positive organisms that do not
effectively produce hydrogen peroxide.’ Dr van der Meer’s paper accords with two reports of C.G.D. in male and female siblings.23 The metabolic studies in family are typical of the oxidative defects of their C.G.D. It may be that their patients and others with autosomal recessive inheritance of the syndrome have a different basic enzymatic defect than those with X-linked disease, but until the specific biochemical defects can be accurately defined, there is no justification for calling this phagocytic defect a new one. Duke
University Medical Center,
Durham, North Carolina 27710, and
University of Alabama, Birmingham, Alabama, U.S.A.
CATHERINE M. WILFERT RICHARD B. JOHNSTON, JR.
RABIES
SIR,-It would be a great help to doctors if holidaymakers, before going abroad, were to learn not to befriend any animal whatsoever. If they do get bitten by a domestic animal such as a dog, the name and address of the owner should be taken, the vaccination status of the animal should be ascertained, and local medical assistance should be sought. Though it is true that duck-embryo vaccine (D.E.v.) has achieved popularity in the U.S.A. and in the U.K. because it is freer from neuroparalytic incidents which follow the older c.N.s. tissue vaccines, doubts have been cast on its efficacy. It is therefore time to produce and evaluate the newer and more powerful (and more expensive) tissue-culture vaccines and subunit vaccines because two or three doses of these vaccines effect the same rise of serum neutralising antibodies as does a full course Of D.E.V. Modern laboratory diagnostic methods have speeded up considerably the diagnosis of rabies, and in many cases there is no need to wait until the suspect animal exhibits signs and sympBellanti, J. A., Dayton, D. H. (editors) The Phagocytic Cell in Host Resistance; p. 225. New York, 1975. 2. Johnston, R. B., Jr., Wilfert, C. M., Buckley, R. H., Webb, L. S. DeChatelet, C. R., McCall, E. D. Lancet, 1975, i, 824. 3. Malawista, S. E., Gifford, R. H. Clin. Res. 1975, 23, 416a. 1.
dies from the disease; also there are diagnostic tests be done on the live animal and may prove positive three days before clinical signs develop in the suspect
toms or
which
can
two or
animal.
Royal Army
Medical
College,
Millbank, London SW1P 4RJ.
ETHELWALD E. VELLA
RADIATION AND PITUITARY FUNCTION IN CHILDREN
StR,—We read with great interest the article by Shalet and others.’ Some of our data on the effect of extracranial irradiation on pituitary function in children are pertinent. 23 They
supplement and even clarify certain points, since our study to only one of the factors in Shalet et al.’s report-namely, radiation. Furthermore, radiation in our group was administered in the absence of recognisable intracranial disease. In addition, our study is prospective and, in the planning, certain questions, such as effects of corticoids or other drugs, 4
refers
taken into account.4 secretion of growth hormone (G.H.) was studied in leukaemic children before and immediately after 18 days of "prophylactic" cranial irradiation. Plasma-G.H. was determined by radioimmunoassay in samples obtained hourly from 8 P.M. to7 A.M. during natural sleep. Cortisone had been discontinued 30-60 days before irradiation, and during irradiation mercaptopurine was given in half the dose used before. Plasma-G.H. values before irradiation were similar to those in normal children, a finding strongly suggesting normal pituitary function before irradiation. Immediately after the end of irradiation, and only 18 days after the first sampling, plasma-G.H. levels were very low. Group A in the report by Shalet et al. was studied 3 months after neurosurgery and, as it seems, 2 weeks after the start of cranial irradiation. Shalet et al. tend to attribute G.H. suppression in group A to the neurosurgical operation and they feel it is unlikely to have been caused by the irradiation, because of the short interval in time. Our data, however, favour such a hypothesis, since suppression of pituitary function was seen quite early. Follow-up of our group, thus far, indicates recovery of pituitary function 6-12 months later, while in Shalet et al.’s report no improvement in pituitary function with time was demonstrated. Two explanations may be offered: (1) with smaller doses of irradiation recovery of function is possible, while with higher doses the damage is permanent in some cases (our children received 2400 rads from a 60CO source; although the radiation dose is not given in Shalet et al.’s data, it must be much higher); (2) the radiation is an unrelated or only a contributing factor and the primary cause of pituitary insufficiency is surgery, as your contributors suggested. The first explanation seems more likely. One may wonder why, for so many years, the healthy pituitary has been considered resistant to conventional irradiation, in the doses usually applied for intracranial disease. The data, so far, even the biochemical data, did not include measurements of G.H., and the most important observations were made in adults. It is tempting to speculate that the pituitary may be more vulnerable to irradiation during the years of active growth, and much more so as far as G.H. and gonadotrophins are concerned. Support for this hypothesis probably emerges from the growth data in atomic-bomb victims.’ It is obvious that more
were
Spontaneous night
1.
Shalet, S. M., Beardwell, C. G., Morrisjone, P. H., Pearson, D. Lancet, July
19, 1975, p. 104. Dacou-Voutetakis, C., Xypolyta, A., Haidas, St., Constantinidis, M., Zannos-Mariolea, L. 13th annual meeting, European Society of Pediatric Endocrinology, Paris, Sept. 12-15, 1974; p. 38. 3. Dacou-Voutetakis, C., Xypolyta, A., Haidas, St., Constantinidis, M., Zannos-Mariolea, L. Ped. Res. 1975, 9, 686. 4. Dacou-Voutetakis, C., Xypolyta, A., Haidas, St., Constantinidis, M., Papavasiliou, C., Zannos-Mariolea, L. J. clin. Endocr. Metab. (in the press). 5. Sutow, W. W., Conard, R. A., Griffith, R. M. Pediatrics, 1965, 36, 721. 2.
