- Email: [email protected]
ANENCEPHALY IN SHIRAZ, IRAN
82
scrutiny of persisted.
a
number of
colleagues,
two
discrepancies
I would advise caution in applying the figures in table ill 1971, since they are now several years out of date, and presumably anxsthetic staffing has changed somewhat since then. The whole purpose of putting table ill in was to show that Birmingham anaesthetists work about as hard as anybody else and still can maintain two large day-release systems. Department of Anæsthetics, Queen Elizabeth Hospital, PETER J. TOMLIN. Birmingham 15.
TABLE
II-CHI-SQUARE RESULTS
OF STUDY-GROUPS IN TABLE I
to
IMMUNOSUPPRESSIVE AGENTS IN CHILDHOOD NEPHROTIC SYNDROME
SIR,-Two controlled studies evaluating the effect of
immunosuppressive agents in the nephrotic syndrome of childhood have lately been reported in The Lancet. In one, an international study-group 1 found that azathioprine had no advantage over a placebo in the treatment of steroid non-responders, and no significant advantage when used in children with frequent relapses. In the second (Barratt and Soothill 2), cyclophosphamide was found to cause a significant reduction in the incidence of relapses, compared to the control group, when used in a similar population of patients. Since one might conclude from these reports that cyclophosphamide is beneficial in children with frequently TABLE I-COMPARISON OF CYCLOPHOSPHAMIDE AND AZATHIOPRINE TRIALS IN CHILDREN WITH
FREQUENTLY
RELAPSING NEPHROTIC
difference exists between the treated groups (azathioprine versus cyclophosphamide X2= 0-43, 0-50 < p < 0-70), nor between the cyclophosphamide group and the control group which received intermittent prednisone Cx2= 2-5, 0-10
no
cyclophosphamide plus prednisone and patients given intermittent prednisone. These results suggest that any conclusion regarding the superiority of a particular immunosuppressive agent in the nephrotic syndrome will depend upon trials which employ comparable control groups or which directly compare them. Departments of Medicine and Pediatrics, Section of Metabolism, Yale University School of Medicine, New Haven, Connecticut 06510.
NORMAN J. SIEGEL JOHN P. HAYSLETT.
SYNDROME**
ANENCEPHALY IN
SiR,ņAnencephaly
*
All data
at
six months
follow-up.
relapsing nephrotic syndrome and azathioprine is not, an analysis of the results is useful. The criteria employed for selecting patients with frequent relapses were similar in each trial, and observation was continued for at least 6 months in both. There was a major difference, however, in the design of the treatment regimens. In the cooperative prospective study, azathioprine plus intermittent prednisone (40 mg. per sq. m. per day given three consecutive days out of seven) was compared to placebo plus intermittent prednisone. In contrast, Barratt and Soothill compared patients who received previous treatment with cyclophosphamide plus prednisone to those receiving previous treatment with prednisone alone. Thus, during the period of observation, the " control " group in the azathioprine study received intermittent prednisone while no treatment was given to the "control" group in the cyclophosphamide study. The results, after 6 months of observation, for both reports are shown in table I and the statistical analysis in table 11. The data demonstrate that the control groups tically significantly different (x2= 6-3, 0-01 < p < 1.
2.
has
Abramowicz, M., Arneil, G. C., Barnett, H. L., Barron, B. A., Edelmann, C. M., Gordillo-P., G., Greifer, I., Hallman, N., Kobayashi, O., Tiddens, H. A. Lancet, 1970, i, 959. Barratt, T. M., Soothill, J. F. ibid. 1970, ii, 479.
SHIRAZ, IRAN peculiar geographical distri-
bution.I There is some evidence that environmental factors play a pathogenic rolebut ethnic background seems to be more important. 3,4 In Israel there is a statistically significant difference between the Ashkenazy and nonAshkenazy populations in the incidence of anencephaly.5 In the Ashkenazy population the incidence is low, and comparable to that in France, Germany, or Switzerland. Among the non-Ashkenazy Israelis it is much higher. One would expect to find a similarly high incidence of anencephaly in the Middle Eastern countries where most of these Jews come from. We have analysed the incidence of anencephaly in the necropsy files of the department of pathology, Pahlavi University School of Medicine, which provides the pathology service to five university-affiliated hospitals in Shiraz. Approximately half the children born in Shiraz are delivered in these hospitals. From August, 1966, to August, 1970, there were 14,520 deliveries. In this period, 23 anencephalic children were observed. Of the 23 children, 13 were girls; and most of the children were born in December. The preponderance of females and the clustering of deliveries with this type of malformation in early winter months is in accord with reports from Europe, but these features are not usually noted in America.4 The calculated incidence is 0-16%, or 1-6 per 1000 births. This is more than twice as high as the incidence recorded in Bombay (0-076%) and in other parts of Asia.1 The incidence is comparable with that reported in non-Ashkenazy Israelis (0-121%).5 Although one cannot exclude some unknown external xtiological factor, the ethnic theory could well explain these findings. Pahlavi University School of
statis0-02). In are
a
Medicine, Shiraz, Iran.
I. DAMYANOV W. DUTZ.
1. Penrose, L. S. J. ment. Def. Res. 1957, 1, 4. 2. Coffey, V. P., Jessop, W. J. E. Br. J. prev. soc. Med. 1957, 11, 174. 3. Naggan, L., MacMahon, B. New Engl. J. Med. 1967, 277, 1119. 4. Cassady, G. Am. J. Obstet. Gynec. 1969, 103, 1154. 5. Halevi, H. S. Br. J. prev. soc. Med. 1967, 21, 66.
scrutiny of persisted.
a
number of
colleagues,
two
discrepancies
I would advise caution in applying the figures in table ill 1971, since they are now several years out of date, and presumably anxsthetic staffing has changed somewhat since then. The whole purpose of putting table ill in was to show that Birmingham anaesthetists work about as hard as anybody else and still can maintain two large day-release systems. Department of Anæsthetics, Queen Elizabeth Hospital, PETER J. TOMLIN. Birmingham 15.
TABLE
II-CHI-SQUARE RESULTS
OF STUDY-GROUPS IN TABLE I
to
IMMUNOSUPPRESSIVE AGENTS IN CHILDHOOD NEPHROTIC SYNDROME
SIR,-Two controlled studies evaluating the effect of
immunosuppressive agents in the nephrotic syndrome of childhood have lately been reported in The Lancet. In one, an international study-group 1 found that azathioprine had no advantage over a placebo in the treatment of steroid non-responders, and no significant advantage when used in children with frequent relapses. In the second (Barratt and Soothill 2), cyclophosphamide was found to cause a significant reduction in the incidence of relapses, compared to the control group, when used in a similar population of patients. Since one might conclude from these reports that cyclophosphamide is beneficial in children with frequently TABLE I-COMPARISON OF CYCLOPHOSPHAMIDE AND AZATHIOPRINE TRIALS IN CHILDREN WITH
FREQUENTLY
RELAPSING NEPHROTIC
difference exists between the treated groups (azathioprine versus cyclophosphamide X2= 0-43, 0-50 < p < 0-70), nor between the cyclophosphamide group and the control group which received intermittent prednisone Cx2= 2-5, 0-10
no
cyclophosphamide plus prednisone and patients given intermittent prednisone. These results suggest that any conclusion regarding the superiority of a particular immunosuppressive agent in the nephrotic syndrome will depend upon trials which employ comparable control groups or which directly compare them. Departments of Medicine and Pediatrics, Section of Metabolism, Yale University School of Medicine, New Haven, Connecticut 06510.
NORMAN J. SIEGEL JOHN P. HAYSLETT.
SYNDROME**
ANENCEPHALY IN
SiR,ņAnencephaly
*
All data
at
six months
follow-up.
relapsing nephrotic syndrome and azathioprine is not, an analysis of the results is useful. The criteria employed for selecting patients with frequent relapses were similar in each trial, and observation was continued for at least 6 months in both. There was a major difference, however, in the design of the treatment regimens. In the cooperative prospective study, azathioprine plus intermittent prednisone (40 mg. per sq. m. per day given three consecutive days out of seven) was compared to placebo plus intermittent prednisone. In contrast, Barratt and Soothill compared patients who received previous treatment with cyclophosphamide plus prednisone to those receiving previous treatment with prednisone alone. Thus, during the period of observation, the " control " group in the azathioprine study received intermittent prednisone while no treatment was given to the "control" group in the cyclophosphamide study. The results, after 6 months of observation, for both reports are shown in table I and the statistical analysis in table 11. The data demonstrate that the control groups tically significantly different (x2= 6-3, 0-01 < p < 1.
2.
has
Abramowicz, M., Arneil, G. C., Barnett, H. L., Barron, B. A., Edelmann, C. M., Gordillo-P., G., Greifer, I., Hallman, N., Kobayashi, O., Tiddens, H. A. Lancet, 1970, i, 959. Barratt, T. M., Soothill, J. F. ibid. 1970, ii, 479.
SHIRAZ, IRAN peculiar geographical distri-
bution.I There is some evidence that environmental factors play a pathogenic rolebut ethnic background seems to be more important. 3,4 In Israel there is a statistically significant difference between the Ashkenazy and nonAshkenazy populations in the incidence of anencephaly.5 In the Ashkenazy population the incidence is low, and comparable to that in France, Germany, or Switzerland. Among the non-Ashkenazy Israelis it is much higher. One would expect to find a similarly high incidence of anencephaly in the Middle Eastern countries where most of these Jews come from. We have analysed the incidence of anencephaly in the necropsy files of the department of pathology, Pahlavi University School of Medicine, which provides the pathology service to five university-affiliated hospitals in Shiraz. Approximately half the children born in Shiraz are delivered in these hospitals. From August, 1966, to August, 1970, there were 14,520 deliveries. In this period, 23 anencephalic children were observed. Of the 23 children, 13 were girls; and most of the children were born in December. The preponderance of females and the clustering of deliveries with this type of malformation in early winter months is in accord with reports from Europe, but these features are not usually noted in America.4 The calculated incidence is 0-16%, or 1-6 per 1000 births. This is more than twice as high as the incidence recorded in Bombay (0-076%) and in other parts of Asia.1 The incidence is comparable with that reported in non-Ashkenazy Israelis (0-121%).5 Although one cannot exclude some unknown external xtiological factor, the ethnic theory could well explain these findings. Pahlavi University School of
statis0-02). In are
a
Medicine, Shiraz, Iran.
I. DAMYANOV W. DUTZ.
1. Penrose, L. S. J. ment. Def. Res. 1957, 1, 4. 2. Coffey, V. P., Jessop, W. J. E. Br. J. prev. soc. Med. 1957, 11, 174. 3. Naggan, L., MacMahon, B. New Engl. J. Med. 1967, 277, 1119. 4. Cassady, G. Am. J. Obstet. Gynec. 1969, 103, 1154. 5. Halevi, H. S. Br. J. prev. soc. Med. 1967, 21, 66.