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PAGET'S DISEASE OF BONE
1170
Summary Patients who have received cortisone are liable to later submitted to the stress of operation There is evidence that this state of shock is the outcome of adrenal insufficiency due to atrophic changes within the adrenal cortex induced by corticosteroid therapy. Death in three patients could be on these grounds. Shock was successfully explained only treated in four other patients by the further administration of cortisone, though one eventually died. It is suggested that cortisone should be administered prophylactically to any patient undergoing operation who has had corticosteroid therapy within a year, and possibly two years, of the operation ; cortisone cover should include the operation-period and be withdrawn during convalescence. A scheme of dosage is proposed. Since this scheme was followed, eight such patients have been treated without collapse in any. The complications usually associated with cortisone therapy must be expected while prophylactic cover is being maintained-especially a tendency to infection and septicaemia. Such infections require larger doses of antibiotics than usual for their control. In any patient for whom corticosteroid therapy is contemplated, careful consideration should be given to the likelihood of operation being needed. Operative risks are increased by antecedent administration of cortisone.
TABLE I-AGE AND SEX DISTRIBUTION IN 689 CASES DIAGNOSED AS PAGET’S DISEASE
collapse when subsequently.
We wish to acknowledge the assistance given by Dr. W. T. Cooke in the preparation of this paper and for permission to record cases under our joint care. We wish to thank Mr. J. C. Edwards for permission to report case 3 and Dr. E. Bulmer for case 4.
most fruitful area of examination for Paget’s disease : thus in the series of Dickson et al. (1945) the pelvis was involved in 243 out of 367 cases and in that of Rosenkrantz et al. (1952) it was involved in 60 out of
pelvis is the
111.
As
sample of the 69,783 patients radiographed six-year period 3000 X-ray record cards during were examined to see what proportion of patients of different sexes and ages had an examination involving the lumbar spine and pelvis area-including, for example, an examination of the urinary tract or a barium enema. From the information thus obtained, it was possible to estimate the total number of patients in whom this area a
this
examined. Table 11 sets out the age and
was
in whom the diagnosis tion of the pelvis and lumbar
patients
TABLE
II-CASES
OF
distribution of the 289 made from examinaspine and in parentheses
sex
was
PAGET’S
DISEASE OF BONE
REFERENCES
Brooke, B. N. (1956a) Lancet, ii, 532. (1956b) Ibid, p. 1175. Fraser, C. G., Preuss, F. S., Bigford, W.D. (1952) J. Amer. med. Ass. 149, 1542. Harnagel, E. E., Kramer, W. G. (1955) Ibid, 158, 1518. Hayes, M. A. (1956) Surgery, 40, 945. Kushlan, S. D. (1956) Gastroenterology, 30, 75. Hench, P. S., Ward, L. E. (1954) In Lukers, F. D. W.: Medical -
-
Uses of Cortisone.
New York.
Lewis, L., Robinson, R. F., Vee, J., Hacker, L. A., Eisen, C. (1953) Ann. intern. Med. 39, 116. Salassa, R. M., Bennett, W. A., Keating, F. R. jun., Sprague, R. G. (1953) J. Amer. med. Ass. 152, 1509. Swinton, N. W. (1956) Proc. R. Soc. Med. 49, 945. Truelove, S. C., Witts, L. J. (1955) Brit. med. J. ii, 1041.
PAGET’S DISEASE OF BONE THE RADIOLOGIGAL INCIDENCE
F. PYGOTT
M.B. Lpool, D.P.H., RADIOLOGIST,
D.M.R.E.
CENTRAL MIDDLESEX
HOSPITAL,
LONDON
LARGE series of cases of Paget’s disease of bone (diagnosed ra,diologically) have been reported by Dickson, Camp, and Ghormley (1945), Brailsford (1938), and others ; but there has been no report of the radiological incidence of the disease at differing ages. Necropsy studies by Schmorl (1932) and Collins (1956) on unselected subjects over 40 years of age have shown an incidence of 3% and 3.7% respectively. In the ten-year period 1947-56, 689 cases of Paget’s disease have been diagnosed in the radiological department of the Central Middlesex Hospital. Table i shows their age and sex distribution. For the six-year period 1947-52 it was possible to divide the 357 cases of Paget’s disease discovered (245 men and 112 women) into two groups according to whether the diagnosis was made initially as a result of an examination which included the lumbar spine and pelvis, There or as a result of examination of any other site. were 289 patients in the first group (204 men and 85 women) and 68 patients in the second group (41 men and 27 women). It is well recognised that, radiologically, the
the estimated number of persons similarly examined in the same age-group. From table n the rate per 1000 persons at different age-groups was calculated (table 111). Only the last group, the 85 +, is too small for any reliable information to be obtained from it. From table ill it appears that the incidence in men alters little from 35 to 54 years but after 55 it increases rapidly to a steady high level which is reached in the decade 6 5-7 4after 7 5 it shows little change. In women the incidence under 55 years is surprisingly similar to that of men of the same age, but after 55 the increase is only to a rate about half that of men of the same age, except possibly in the 85+ group where the rate rises sharply to the male level. Taking the average of both sexes combined over the age of 45 years (279 patients with Paget’s disease among 9775 examined) the incidence of 3-5% is surprisingly near that of Collins for subjects over 40 years of age. It is of interest that in the larger series of 689 cases of disease only 3 sarcomas were encountered-one in a man of 78 with extensive Paget’s disease in the pelvis and both femora who had developed an osteolytic- lesion of his
Paget’s
TABLE
III-PAGET’S
DISEASE OF BONE
(RATE
PER
1000)
1171 another in a man of 56 with an osteolytic lesion ilium who had Paget’s disease limited to the in a woman of 58 who had an osteopelvis ; and the third chondro-sarcoma of the sacrum as well as Paget’s disease of the pelvis.
right femur ; in the right
Summary
SEASONAL INCIDENCE OF MEGALOBLASTIC ANÆMIA OF PREGNANCY AND THE PUERPERIUM R. B. THOMPSON M.D. Durh., M.R.C.P. MEDICINE,
KING’S
COLLEGE,
UNIVERSITY
OF
AND ASSISTANT PHYSICIAN, PRINCESS MARY MATERNITY HOSPITAL, NEWCASTLE UPON TYNE
DURHAM,
MEGALOBLASTic anaemia of pregnancy in the tropics is generally considered to be due to nutritional deficiency ; patients often respond to vitamin-B12 therapy, although folic-acid and other deficiencies are often present as well. The role of dietary deficiency in the aetiology of megaloblastic anaemia of pregnancy in temperate climates is, however, by no means so certain. If dietary deficiency is a significant factor, more patients might be expected to develop the disorder during the winter and spring than during the summer and autumn (see below). The present study was made to find if any such seasonal variation existed. Methods
The hsematological methods were essentially the same those described by Thompson and Ungley (1951). In all the present cases megaloblastic erythropoiesis was found either by marrow biopsy, blood-film, or buffy-coat All the recent cases responded smear (Goodall 1955). satisfactorily to folic acid ; the treatments used in the earlier cases have previously been described (Thompson and Ungley 1951). The date of delivery was always readily obtained. The date of onset of anaemia could not be determined with any accuracy in most of the patients ; it could, however, usually be assessed to within about a month. Errors of a month, or even of two months, would not effect the main conclusions, for the onset of symptoms was always either about the time of delivery or, more commonly, about the 7th-8th month of pregnancy. Since full blood examinations have been made for some years on all patients attending the antenatal clinic in whom the Hb Was less than 70%, the date of onset of anaemia could often be ascertained to within a month. Unfortunately, many patients were admitted late in pregnancy or in the puerperium, and the date of onset had to be assessed from the patient’s symptoms and from data supplied by as
was
a
guide, especially when taken with the onset of symptoms such as general tiredness, loss of appetite,
vomiting, pallor, and breathlessness. Material
The caserecords of 105
patients
REFERENCES
Brailsford, J. F. (1938) Brit. J. Radiol. ii, 507. Collins, D. H. (1956) Lancet, ii, 51. Dickson, D. D., Camp, J. D., Ghormley, R. K. (1945) Radiology, 44, 449. Rosenkrantz, J. H., Wolf, J., Kaicher, J. J. (1952) Arch. intern. Med. 90, 610. Schmorl, G. (1932) Virchows Arch. 283, 694.
IN
tongue useful
A consecutive series of 689 patients with Paget’s disease is reported. In part of the series it was possible to correlate the number of radiographic examinations which included the lumbar spine and pelvis with the number of cases of Paget’s disease so encountered. The incidence of Paget’s disease in both sexes was nearly equal below the age of 54 years but thereafter the male rate rose rapidly to a high level in the period 65-74 when it was approximately double the female rate. Above the age of 75 the male rate showed little alteration. In women the rate appeared to rise sharply to the male level over the age of 85. Sarcoma was encountered only 3 times in the series.
LECTURER
the family doctor. Soreness or ulceration of the
were
available for this study: 36 from a general
hospital,
to
of onset of megaloblastic an-4’t"la which most Monthly incidence and of parturition. of them were admitted in the puerperium ; 55 from one maternity hospital; and 14 from another. In neither of the maternity hospitals was there any seasonal variation in the number of deliveries. The lst patient of the series was seen in 1933 and all available cases were included up to October, 1956. In recent years, since the clinical and haematological picture has become better recognised, most patients have been diagnosed during pregnancy, whereas most of the earlier cases were
puerperal.
In 5 patients the dates of delivery are known, and these are included in parentheses in the accompanying table ; it was, however, impossible to assess the date of onset of symptoms in these patients, and they have not been included in the main analysis or in the accompany-
ing figure. Results
The results are presented in the figure and the table, which show that there were significantly more deliveries in the six-month period from February to July inclusive than during the other half of the year. Since the onset of the disorder is commonly about two months before delivery, the table and the figure show a similar seasonal incidence but in an earlier six-month period. Thus the onset was in the period December-May in 70 and the period June-November in 30.
patients.
Discussion
The results are most readily explained by postulating that dietary deficiency during the winter months plays a significant part in the aetiology of megaloblastic anaemia. of pregnancy. That such a factor is important in scurvy has been long recognised ; indeed it was the possible analogy with scurvy that suggested the present study. The richest animal source of folic acid is liver, the total folic-acid content of 100 g. of beef liver being stated by MONTHLY
INCIDENCE OF ONSET OF MEGALOBLASTIC AND OF PARTURITION
AN1FMIA.
The figures in parentheses refer to 5 patients in whom the date of onset of anaemia could not be assessed.
Summary Patients who have received cortisone are liable to later submitted to the stress of operation There is evidence that this state of shock is the outcome of adrenal insufficiency due to atrophic changes within the adrenal cortex induced by corticosteroid therapy. Death in three patients could be on these grounds. Shock was successfully explained only treated in four other patients by the further administration of cortisone, though one eventually died. It is suggested that cortisone should be administered prophylactically to any patient undergoing operation who has had corticosteroid therapy within a year, and possibly two years, of the operation ; cortisone cover should include the operation-period and be withdrawn during convalescence. A scheme of dosage is proposed. Since this scheme was followed, eight such patients have been treated without collapse in any. The complications usually associated with cortisone therapy must be expected while prophylactic cover is being maintained-especially a tendency to infection and septicaemia. Such infections require larger doses of antibiotics than usual for their control. In any patient for whom corticosteroid therapy is contemplated, careful consideration should be given to the likelihood of operation being needed. Operative risks are increased by antecedent administration of cortisone.
TABLE I-AGE AND SEX DISTRIBUTION IN 689 CASES DIAGNOSED AS PAGET’S DISEASE
collapse when subsequently.
We wish to acknowledge the assistance given by Dr. W. T. Cooke in the preparation of this paper and for permission to record cases under our joint care. We wish to thank Mr. J. C. Edwards for permission to report case 3 and Dr. E. Bulmer for case 4.
most fruitful area of examination for Paget’s disease : thus in the series of Dickson et al. (1945) the pelvis was involved in 243 out of 367 cases and in that of Rosenkrantz et al. (1952) it was involved in 60 out of
pelvis is the
111.
As
sample of the 69,783 patients radiographed six-year period 3000 X-ray record cards during were examined to see what proportion of patients of different sexes and ages had an examination involving the lumbar spine and pelvis area-including, for example, an examination of the urinary tract or a barium enema. From the information thus obtained, it was possible to estimate the total number of patients in whom this area a
this
examined. Table 11 sets out the age and
was
in whom the diagnosis tion of the pelvis and lumbar
patients
TABLE
II-CASES
OF
distribution of the 289 made from examinaspine and in parentheses
sex
was
PAGET’S
DISEASE OF BONE
REFERENCES
Brooke, B. N. (1956a) Lancet, ii, 532. (1956b) Ibid, p. 1175. Fraser, C. G., Preuss, F. S., Bigford, W.D. (1952) J. Amer. med. Ass. 149, 1542. Harnagel, E. E., Kramer, W. G. (1955) Ibid, 158, 1518. Hayes, M. A. (1956) Surgery, 40, 945. Kushlan, S. D. (1956) Gastroenterology, 30, 75. Hench, P. S., Ward, L. E. (1954) In Lukers, F. D. W.: Medical -
-
Uses of Cortisone.
New York.
Lewis, L., Robinson, R. F., Vee, J., Hacker, L. A., Eisen, C. (1953) Ann. intern. Med. 39, 116. Salassa, R. M., Bennett, W. A., Keating, F. R. jun., Sprague, R. G. (1953) J. Amer. med. Ass. 152, 1509. Swinton, N. W. (1956) Proc. R. Soc. Med. 49, 945. Truelove, S. C., Witts, L. J. (1955) Brit. med. J. ii, 1041.
PAGET’S DISEASE OF BONE THE RADIOLOGIGAL INCIDENCE
F. PYGOTT
M.B. Lpool, D.P.H., RADIOLOGIST,
D.M.R.E.
CENTRAL MIDDLESEX
HOSPITAL,
LONDON
LARGE series of cases of Paget’s disease of bone (diagnosed ra,diologically) have been reported by Dickson, Camp, and Ghormley (1945), Brailsford (1938), and others ; but there has been no report of the radiological incidence of the disease at differing ages. Necropsy studies by Schmorl (1932) and Collins (1956) on unselected subjects over 40 years of age have shown an incidence of 3% and 3.7% respectively. In the ten-year period 1947-56, 689 cases of Paget’s disease have been diagnosed in the radiological department of the Central Middlesex Hospital. Table i shows their age and sex distribution. For the six-year period 1947-52 it was possible to divide the 357 cases of Paget’s disease discovered (245 men and 112 women) into two groups according to whether the diagnosis was made initially as a result of an examination which included the lumbar spine and pelvis, There or as a result of examination of any other site. were 289 patients in the first group (204 men and 85 women) and 68 patients in the second group (41 men and 27 women). It is well recognised that, radiologically, the
the estimated number of persons similarly examined in the same age-group. From table n the rate per 1000 persons at different age-groups was calculated (table 111). Only the last group, the 85 +, is too small for any reliable information to be obtained from it. From table ill it appears that the incidence in men alters little from 35 to 54 years but after 55 it increases rapidly to a steady high level which is reached in the decade 6 5-7 4after 7 5 it shows little change. In women the incidence under 55 years is surprisingly similar to that of men of the same age, but after 55 the increase is only to a rate about half that of men of the same age, except possibly in the 85+ group where the rate rises sharply to the male level. Taking the average of both sexes combined over the age of 45 years (279 patients with Paget’s disease among 9775 examined) the incidence of 3-5% is surprisingly near that of Collins for subjects over 40 years of age. It is of interest that in the larger series of 689 cases of disease only 3 sarcomas were encountered-one in a man of 78 with extensive Paget’s disease in the pelvis and both femora who had developed an osteolytic- lesion of his
Paget’s
TABLE
III-PAGET’S
DISEASE OF BONE
(RATE
PER
1000)
1171 another in a man of 56 with an osteolytic lesion ilium who had Paget’s disease limited to the in a woman of 58 who had an osteopelvis ; and the third chondro-sarcoma of the sacrum as well as Paget’s disease of the pelvis.
right femur ; in the right
Summary
SEASONAL INCIDENCE OF MEGALOBLASTIC ANÆMIA OF PREGNANCY AND THE PUERPERIUM R. B. THOMPSON M.D. Durh., M.R.C.P. MEDICINE,
KING’S
COLLEGE,
UNIVERSITY
OF
AND ASSISTANT PHYSICIAN, PRINCESS MARY MATERNITY HOSPITAL, NEWCASTLE UPON TYNE
DURHAM,
MEGALOBLASTic anaemia of pregnancy in the tropics is generally considered to be due to nutritional deficiency ; patients often respond to vitamin-B12 therapy, although folic-acid and other deficiencies are often present as well. The role of dietary deficiency in the aetiology of megaloblastic anaemia of pregnancy in temperate climates is, however, by no means so certain. If dietary deficiency is a significant factor, more patients might be expected to develop the disorder during the winter and spring than during the summer and autumn (see below). The present study was made to find if any such seasonal variation existed. Methods
The hsematological methods were essentially the same those described by Thompson and Ungley (1951). In all the present cases megaloblastic erythropoiesis was found either by marrow biopsy, blood-film, or buffy-coat All the recent cases responded smear (Goodall 1955). satisfactorily to folic acid ; the treatments used in the earlier cases have previously been described (Thompson and Ungley 1951). The date of delivery was always readily obtained. The date of onset of anaemia could not be determined with any accuracy in most of the patients ; it could, however, usually be assessed to within about a month. Errors of a month, or even of two months, would not effect the main conclusions, for the onset of symptoms was always either about the time of delivery or, more commonly, about the 7th-8th month of pregnancy. Since full blood examinations have been made for some years on all patients attending the antenatal clinic in whom the Hb Was less than 70%, the date of onset of anaemia could often be ascertained to within a month. Unfortunately, many patients were admitted late in pregnancy or in the puerperium, and the date of onset had to be assessed from the patient’s symptoms and from data supplied by as
was
a
guide, especially when taken with the onset of symptoms such as general tiredness, loss of appetite,
vomiting, pallor, and breathlessness. Material
The caserecords of 105
patients
REFERENCES
Brailsford, J. F. (1938) Brit. J. Radiol. ii, 507. Collins, D. H. (1956) Lancet, ii, 51. Dickson, D. D., Camp, J. D., Ghormley, R. K. (1945) Radiology, 44, 449. Rosenkrantz, J. H., Wolf, J., Kaicher, J. J. (1952) Arch. intern. Med. 90, 610. Schmorl, G. (1932) Virchows Arch. 283, 694.
IN
tongue useful
A consecutive series of 689 patients with Paget’s disease is reported. In part of the series it was possible to correlate the number of radiographic examinations which included the lumbar spine and pelvis with the number of cases of Paget’s disease so encountered. The incidence of Paget’s disease in both sexes was nearly equal below the age of 54 years but thereafter the male rate rose rapidly to a high level in the period 65-74 when it was approximately double the female rate. Above the age of 75 the male rate showed little alteration. In women the rate appeared to rise sharply to the male level over the age of 85. Sarcoma was encountered only 3 times in the series.
LECTURER
the family doctor. Soreness or ulceration of the
were
available for this study: 36 from a general
hospital,
to
of onset of megaloblastic an-4’t"la which most Monthly incidence and of parturition. of them were admitted in the puerperium ; 55 from one maternity hospital; and 14 from another. In neither of the maternity hospitals was there any seasonal variation in the number of deliveries. The lst patient of the series was seen in 1933 and all available cases were included up to October, 1956. In recent years, since the clinical and haematological picture has become better recognised, most patients have been diagnosed during pregnancy, whereas most of the earlier cases were
puerperal.
In 5 patients the dates of delivery are known, and these are included in parentheses in the accompanying table ; it was, however, impossible to assess the date of onset of symptoms in these patients, and they have not been included in the main analysis or in the accompany-
ing figure. Results
The results are presented in the figure and the table, which show that there were significantly more deliveries in the six-month period from February to July inclusive than during the other half of the year. Since the onset of the disorder is commonly about two months before delivery, the table and the figure show a similar seasonal incidence but in an earlier six-month period. Thus the onset was in the period December-May in 70 and the period June-November in 30.
patients.
Discussion
The results are most readily explained by postulating that dietary deficiency during the winter months plays a significant part in the aetiology of megaloblastic anaemia. of pregnancy. That such a factor is important in scurvy has been long recognised ; indeed it was the possible analogy with scurvy that suggested the present study. The richest animal source of folic acid is liver, the total folic-acid content of 100 g. of beef liver being stated by MONTHLY
INCIDENCE OF ONSET OF MEGALOBLASTIC AND OF PARTURITION
AN1FMIA.
The figures in parentheses refer to 5 patients in whom the date of onset of anaemia could not be assessed.