- Email: [email protected]
AUDITORY DISTURBANCE DUE TO TRISOMY 22
276 the few less four hairs area The than examined. problem per our controls of our was 73 and of patients years, average age was 71 years. In each group, there were 4 under 60 years of age and 9 over 80 years of age. 15 patients and 10 controls had no hair on either leg or toes, 11 patients and 16 controls had hair on leg or toes but not on both, and 14 patients and 16 controls had hair on both leg and toes (chi-squared test, two degrees of freedom, not significant). We cannot, therefore, confirm the widely held view that hairlessness of the lower limb is a sign of occlusive arterial disease. We thank the consultants of St. Finbarr’s Hospital for giving us access to their patients, and Prof. M. A. Moran, department of statis-
of hairs. Our
arbitrary definition of hairlessness for
cases was
tics, University College, Cork.
Age-structure in North Swedish population 1950-70.
Average population size 8000. ratio of 122 per 1000 deaths as compared with 163 per 1000 in the general Swedish population (r <0.003, table). The types and sites of the malignant tumours were not significantly different in the two populations. During 1950-70 the- age structure of this population changed significantly through outmigration, mainly from its younger cohorts (see figure). In such an ageing population an increase in cancer mortality would be expected. Genetic vulnerability for schizophrenic psychosis in this geographically isolated population in which all known patients over the past 75 years have been related to one another appears to be associated with a combination of low variates of two genetic enzyme systems affecting catecholamine metabolism (dopamine-p-hydroxylase and monoamine oxidase5). Since both genes producing low activities must have a high frequency in this population a biochemical and genetic link between schizophrenia as well as certain carriers and reduced liability for the development of malignant neoplasms is an interesting possibility. A parallel hypothesis concerning methionine metabolism (methionine adenosyltransferase) catecholamines, schizophrenia, and malignant neoplasm has been suggested by Levi and Waxman.6 Both suggestions have the merit of experimental testability. to a
Institute for Medical Genetics, S-752 20 Uppsala, Sweden
NOLLAIG PARFREY JOHN F. RYAN LAURA SHANAHAN MICHAEL P. BRADY
Department of Surgery, University College, Cork, Ireland
AUDITORY DISTURBANCE DUE TO TRISOMY 22
SIR,-Since the first identification of trisomy 22 by isotopic labelling,more than twenty cases have been referred to in the literature2 as trisomy-22 syndrome. The phenotype of trisomy 22 is a well-defined distinctive syndrome. The ears are characteristically large, posteriorly rotated, and low-set. The external auditory canal can be atresic. Moreover, anomalies of the preauricular region are constantly present-papillomas, cutaneous or cartilaginous tubercules, or sinuses.3 However, 1. Hsu, L. Y. F., Shapiro, L. R., Gertner, M., Lieber, E., Hirschhorn, K. J. Pediat. 1971, 79, 12. 2. Yunis, J. J. New Chromosomal Syndromes. New York, 1977. 3. de Grouchy, J., Turleau, C. Clinical Atlas of Human Chromosomes. New
York,1977.
K. MODRZEWSKA
J. A. BÖÖK
HAIRLESS LOWER LIMBS AND OCCLUSIVE ARTERIAL DISEASE
SIR,-It is accepted-and popular medical and surgical textbooks confirm’-that occlusive arterial disease of the lower limbs is associated with loss of hair on the toes and leg. To investigate the reliability of this widely quoted physical sign, we examined 40 patients in the surgical professorial unit of St. Finbarr’s Hospital, Cork, diagnosed as having occlusive arterial disease of the lower limb, and all had absent pedal pulses. 40 controls were drawn from the medical wards of the same hospital and had no symptoms or signs of vascular disease of the lower limb. We counted the hairs of three separate areas of each leg. These areas were: the toes taken together, a 20 cm2 area at the tibial tuberosity, and a 26 cm2 area midway down the shin. There was little difficulty in deciding whether a patient was hairless or not. The vast majority either had no hairs in the examined areas or had a reasonable supply -
5. Book, J. A., Wetterberg, L., Modrzewska, K. Clin. Genet. 1978, 14, 373. 6. Levi, R. N., Waxman, S. Lancet, 1975, ii, 11. 1. Davidson’s Principles and Practice of Medicine, p. 239, (1977); Beeson and McDermott’s Textbook of Medicine, p. 1070 (1975); Harrison’s Principles of Internal Medicine, p. 1323 (1977); Ellis and Calne’s Lecture Notes on General Surgery, p. 67 (1977); Schwartz’ Principles of Surgery, p. 842 (1974); and Davis-Christopher’s Textbook of Surgery, p. 1698 (1972).
v
_
_
-
Results of clinical eaaminations of
-
auditory brainstem-response
(BSR). A-1: +22. A-2: +22q-. i = response of cochlear nerve; iii = response of superior olivary nucleus; v response of inferior colliculi of =
midbrain.
277 little is known about auditory function. We have investigated auditory function in complete and in partial trisomy 22. In the complete trisomy 22 (47,XY,+22),4 the left external auditory canal has a small cutaneous septum without atresia. In contrast, partial trisomy 22 (47,XY,+22q—[ql3]) shows no anomalies in the external auditory canal. The examination of auditory brainstem response resulted in -85dB for complete trisomy 22 but -70dB for partial trisomy 22 (see figure). The disturbance of the auditory function is more severe in complete trisomy 22 than in the partial trisomy. TAKASHI KATANO Pædiatric Department, HIDEKI YAMAOKA Hiroshima City Hospital, TAKASHI TAKIGUCHI Motomachi, Hiroshima, Japan Kadotani Medical Research Foundation,
Saijo, Higashihiroshima
TETSUJI KADOTANI
PITFALLS IN EARLY DETECTION OF ECTOPIC PREGNANCY
SIR,-The diagnosis of pregnancy by radioreceptor assay for human chorionic gonadotrophins (&bgr;-H.C.G.) was introduced in 1974.1 This sensitive, specific, and rapid assay permits detection of conception as early as 7 days post-ovulation. We have used the &bgr;-H.C.G. test routinely for the past 2 years to establish early normal and abnormal pregnancies. The test was positive in sixty-two women with suspected ectopic pregnancy, subsequently proved by laparoscopy and laparotomy. Three patients underwent a second laparoscopy before laparotomy, and only on the second intervention was a tubal mass seen. The following case illustrates the limitation of laparoscopy in detecting very early pregnancy. A 26-year-old woman was admitted because of pain in the right lower abdominal quadrant, missed period of 5 days, and a p-H.c.G. of 75 mi.u./ml. The uterus was normal and no adnexal mass was palpable. Examination under anaesthesia did not reveal any pathological findings; on curettage the endometrial tissue was not commensurate with pregnancy. At laparoscopy the uterus, tubes, and ovaries were congested but normal; there was no blood in the abdominal cavity. Early complete abortion was diagnosed, and the patient was sent home. 5 days later she was readmitted because of continuous vaginal bleeding and right lower abdominal pains. A 4x4 cm mass was palpated on the right side of the uterus. The pregnancy test demonstrated 200 mi.u. &bgr;-H.C.G./ml blood. At the second laparoscopy, 7 days after the first, a mass was clearly seen in the ampullary part of the right tube. The patient was immediately operated upon, and the clinical diagnosis of right tubal pregnancy was confirmed. The p-H.C.G. test could well detect very early pregnancy, even before macroscopic pathological changes in the tube can be distinguished. This supposition accords with the embryo studies of Patten2who found that at 18 days the conceptus is less than 10 mm long. It is imperative to determine tubal pregnancy as soon as possible to prevent rupture of the tubes, especially now that procedures such as microsurgery permit reconstruction and preservation of the tubes for future fertility. Very early ectopic pregnancy may not be detectable by laparoscopy. However, when the &bgr;-H.C.G. test is positive-and an intrauterine pregnancy has been ruled out-extrauterine pregnancy should be seriously considered. In such cases, laparoscopy is advocated. When nothing abnormal is seen, the -H.c.G. test should be repeated every week to either confirm or exclude ectopic pregnancy. H. YAFFE Department of Obstetrics and Gynæcology, D. NAVOT Hadassah University Hospital, Em Kerem, Jerusalem, Israel N. LAUFER 4.
Kadotam, T., Katano, T., Yamaoka, H., Murakami, M., Nakamoto, Y.,
Watanabe, V. Proc. Japan Acad. 1978, 54, B, 163. 5
Kadotani, T., Katano, T., Yamamoto, H., Murakami, M., Nakamoto, Y., Watanabe, Y. ibid, p. 217. 1. Rosal, T. P., Saxema, B. B., Landesman, R. Fertil. Steril. 1975, 26, 1105. 2. Patten, B. M. Human Embryology, p.145. New York, 1968.
SPRUE AND SUBCLINICAL MALABSORPTION IN THE TROPICS
SIR,-In their description of a high prevalence of morphoabnormalities of the small bowel among symptom-free persons in Southern Peru, Perea and colleagues wondered whether these changes might represent a subclinical form of tropical sprue. Their suggestion is based on my 1967 hypothesis2 that overt tropical sprue and subclinical malabsorption among residents of tropical areas where sprue is endemic represent different manifestations, in terms of clinical presentation and pathological severity, of the same disease process of which overt tropical sprue represents the clinically recognisable "tip of the iceberg". Perhaps there should be a statute of limitations for any such hypothesis; after a decade it should be reconsidered in light of the information available when it was first put forward, re-examined in terms of subsequently acquired facts, and then be reaffirmed, modified, or discarded. In 1967 information on subclinical malabsorption was confined to that from two tropical countries, South India and Haiti, both of which are endemic for sprue.34 In these areas adults showed a spectrum in the severity of symptoms, intestinal abnormalities, and nutritional deficiencies, varying from mild to moderate among relatively symptom-free persons to severe in overt sprue. It seemed reasonable at that time to conjecture that these abnormalities represent varied manifestations of the same disease process. This concept was supported by a failure to identify, by light or electron microscopy, any basic difference between the intestinal structural abnormalities in sprue and subclinical malabsorption,S and by the observation that treatment with folic acid and/or tetracycline improved the intestinal lesion in persons recognised to have sprue and in some with subclinical malabsorption.6 It now seems, however, that sprue and subclinical malabsorption represent different clinical entities in many instances. Subclinical intestinal abnormalities have now been described among residents of areas such as those described by Perea et al. where sprue does not occur and, in this circumstance, they clearly are unrelated to sprue. Such is undoubtedly also the case in many instances in areas where sprue is endemic, particularly in children among whom sprue is rare. The distinction remains less clear in some adults, however, due in large part to our inability to define precisely what constitutes tropical sprue. In 1971, Baker and I advocated that the rigid criteria for the diagnosis of sprue, such as megaloblastic anaemia, should be modified and that this disorder should be considered as a syndrome which is characterised by structural abnormalities and malabsorption of two distinct substances.7 This definition, which would encompass from 11 % of the population in Puerto Rico to 43% in Haiti,s requires further modification. Firstly, it fails to take into consideration the fact that in sprue symptoms (if present) and intestinal abnormalities get relentlessly worse until specific therapy is instituted, whereas the picture in subclinical malabsorption seems to vary only slightly over time, either improving or worsening.8 9 Secondly, although subclinical malabsorption may contribute to nutritional deficiencies where dietary intake is marginal or inadequate8 it is rarely severe enough to produce the multiple, severe nutritional deficiences characteristic of advanced sprue. Thirdly, the key role of folate or vitamin-B12 deficiency, which
logical
D., Fernan-Zegarra, L., Cruz, V. M., Ballon, R., Picoaga, J. L. Lancet, 1978, ii, 550. 2. Klipstein, F. A. Ann. intern. Med. 1967, 66, 622. 3. Baker, S. J. Indian J. med. Sci. 1957, 11, 687. 4. Klipstein, F. A., Samloff, I. M., Schenk, E. A. Ann. intern. Med. 1966, 64, 1. Perea, V.
575. 5. Brunser, O., Eidelman, S., Klipstein, F. A. Gastroenterology, 1970, 58, 655. 6. Klipstein, F. A., Samloff, I. M., Smarth, G., Schenk, E. A. Gut, 1969, 10, 315. 7. Klipstein, F. A., Baker, S. J. Gastroenterology, 1970, 58, 717. 8. Klipstein, F. A. in Gastroenterology, vol. ii (edited by H. L. Bockus); p. 285.
Philadelphia, 1976. 9. Lindenbaum, J., Jamiul Alam, A. K. M., Kent, T. H. Br. med. J. 1966, ii, 1616.
of hairs. Our
arbitrary definition of hairlessness for
cases was
tics, University College, Cork.
Age-structure in North Swedish population 1950-70.
Average population size 8000. ratio of 122 per 1000 deaths as compared with 163 per 1000 in the general Swedish population (r <0.003, table). The types and sites of the malignant tumours were not significantly different in the two populations. During 1950-70 the- age structure of this population changed significantly through outmigration, mainly from its younger cohorts (see figure). In such an ageing population an increase in cancer mortality would be expected. Genetic vulnerability for schizophrenic psychosis in this geographically isolated population in which all known patients over the past 75 years have been related to one another appears to be associated with a combination of low variates of two genetic enzyme systems affecting catecholamine metabolism (dopamine-p-hydroxylase and monoamine oxidase5). Since both genes producing low activities must have a high frequency in this population a biochemical and genetic link between schizophrenia as well as certain carriers and reduced liability for the development of malignant neoplasms is an interesting possibility. A parallel hypothesis concerning methionine metabolism (methionine adenosyltransferase) catecholamines, schizophrenia, and malignant neoplasm has been suggested by Levi and Waxman.6 Both suggestions have the merit of experimental testability. to a
Institute for Medical Genetics, S-752 20 Uppsala, Sweden
NOLLAIG PARFREY JOHN F. RYAN LAURA SHANAHAN MICHAEL P. BRADY
Department of Surgery, University College, Cork, Ireland
AUDITORY DISTURBANCE DUE TO TRISOMY 22
SIR,-Since the first identification of trisomy 22 by isotopic labelling,more than twenty cases have been referred to in the literature2 as trisomy-22 syndrome. The phenotype of trisomy 22 is a well-defined distinctive syndrome. The ears are characteristically large, posteriorly rotated, and low-set. The external auditory canal can be atresic. Moreover, anomalies of the preauricular region are constantly present-papillomas, cutaneous or cartilaginous tubercules, or sinuses.3 However, 1. Hsu, L. Y. F., Shapiro, L. R., Gertner, M., Lieber, E., Hirschhorn, K. J. Pediat. 1971, 79, 12. 2. Yunis, J. J. New Chromosomal Syndromes. New York, 1977. 3. de Grouchy, J., Turleau, C. Clinical Atlas of Human Chromosomes. New
York,1977.
K. MODRZEWSKA
J. A. BÖÖK
HAIRLESS LOWER LIMBS AND OCCLUSIVE ARTERIAL DISEASE
SIR,-It is accepted-and popular medical and surgical textbooks confirm’-that occlusive arterial disease of the lower limbs is associated with loss of hair on the toes and leg. To investigate the reliability of this widely quoted physical sign, we examined 40 patients in the surgical professorial unit of St. Finbarr’s Hospital, Cork, diagnosed as having occlusive arterial disease of the lower limb, and all had absent pedal pulses. 40 controls were drawn from the medical wards of the same hospital and had no symptoms or signs of vascular disease of the lower limb. We counted the hairs of three separate areas of each leg. These areas were: the toes taken together, a 20 cm2 area at the tibial tuberosity, and a 26 cm2 area midway down the shin. There was little difficulty in deciding whether a patient was hairless or not. The vast majority either had no hairs in the examined areas or had a reasonable supply -
5. Book, J. A., Wetterberg, L., Modrzewska, K. Clin. Genet. 1978, 14, 373. 6. Levi, R. N., Waxman, S. Lancet, 1975, ii, 11. 1. Davidson’s Principles and Practice of Medicine, p. 239, (1977); Beeson and McDermott’s Textbook of Medicine, p. 1070 (1975); Harrison’s Principles of Internal Medicine, p. 1323 (1977); Ellis and Calne’s Lecture Notes on General Surgery, p. 67 (1977); Schwartz’ Principles of Surgery, p. 842 (1974); and Davis-Christopher’s Textbook of Surgery, p. 1698 (1972).
v
_
_
-
Results of clinical eaaminations of
-
auditory brainstem-response
(BSR). A-1: +22. A-2: +22q-. i = response of cochlear nerve; iii = response of superior olivary nucleus; v response of inferior colliculi of =
midbrain.
277 little is known about auditory function. We have investigated auditory function in complete and in partial trisomy 22. In the complete trisomy 22 (47,XY,+22),4 the left external auditory canal has a small cutaneous septum without atresia. In contrast, partial trisomy 22 (47,XY,+22q—[ql3]) shows no anomalies in the external auditory canal. The examination of auditory brainstem response resulted in -85dB for complete trisomy 22 but -70dB for partial trisomy 22 (see figure). The disturbance of the auditory function is more severe in complete trisomy 22 than in the partial trisomy. TAKASHI KATANO Pædiatric Department, HIDEKI YAMAOKA Hiroshima City Hospital, TAKASHI TAKIGUCHI Motomachi, Hiroshima, Japan Kadotani Medical Research Foundation,
Saijo, Higashihiroshima
TETSUJI KADOTANI
PITFALLS IN EARLY DETECTION OF ECTOPIC PREGNANCY
SIR,-The diagnosis of pregnancy by radioreceptor assay for human chorionic gonadotrophins (&bgr;-H.C.G.) was introduced in 1974.1 This sensitive, specific, and rapid assay permits detection of conception as early as 7 days post-ovulation. We have used the &bgr;-H.C.G. test routinely for the past 2 years to establish early normal and abnormal pregnancies. The test was positive in sixty-two women with suspected ectopic pregnancy, subsequently proved by laparoscopy and laparotomy. Three patients underwent a second laparoscopy before laparotomy, and only on the second intervention was a tubal mass seen. The following case illustrates the limitation of laparoscopy in detecting very early pregnancy. A 26-year-old woman was admitted because of pain in the right lower abdominal quadrant, missed period of 5 days, and a p-H.c.G. of 75 mi.u./ml. The uterus was normal and no adnexal mass was palpable. Examination under anaesthesia did not reveal any pathological findings; on curettage the endometrial tissue was not commensurate with pregnancy. At laparoscopy the uterus, tubes, and ovaries were congested but normal; there was no blood in the abdominal cavity. Early complete abortion was diagnosed, and the patient was sent home. 5 days later she was readmitted because of continuous vaginal bleeding and right lower abdominal pains. A 4x4 cm mass was palpated on the right side of the uterus. The pregnancy test demonstrated 200 mi.u. &bgr;-H.C.G./ml blood. At the second laparoscopy, 7 days after the first, a mass was clearly seen in the ampullary part of the right tube. The patient was immediately operated upon, and the clinical diagnosis of right tubal pregnancy was confirmed. The p-H.C.G. test could well detect very early pregnancy, even before macroscopic pathological changes in the tube can be distinguished. This supposition accords with the embryo studies of Patten2who found that at 18 days the conceptus is less than 10 mm long. It is imperative to determine tubal pregnancy as soon as possible to prevent rupture of the tubes, especially now that procedures such as microsurgery permit reconstruction and preservation of the tubes for future fertility. Very early ectopic pregnancy may not be detectable by laparoscopy. However, when the &bgr;-H.C.G. test is positive-and an intrauterine pregnancy has been ruled out-extrauterine pregnancy should be seriously considered. In such cases, laparoscopy is advocated. When nothing abnormal is seen, the -H.c.G. test should be repeated every week to either confirm or exclude ectopic pregnancy. H. YAFFE Department of Obstetrics and Gynæcology, D. NAVOT Hadassah University Hospital, Em Kerem, Jerusalem, Israel N. LAUFER 4.
Kadotam, T., Katano, T., Yamaoka, H., Murakami, M., Nakamoto, Y.,
Watanabe, V. Proc. Japan Acad. 1978, 54, B, 163. 5
Kadotani, T., Katano, T., Yamamoto, H., Murakami, M., Nakamoto, Y., Watanabe, Y. ibid, p. 217. 1. Rosal, T. P., Saxema, B. B., Landesman, R. Fertil. Steril. 1975, 26, 1105. 2. Patten, B. M. Human Embryology, p.145. New York, 1968.
SPRUE AND SUBCLINICAL MALABSORPTION IN THE TROPICS
SIR,-In their description of a high prevalence of morphoabnormalities of the small bowel among symptom-free persons in Southern Peru, Perea and colleagues wondered whether these changes might represent a subclinical form of tropical sprue. Their suggestion is based on my 1967 hypothesis2 that overt tropical sprue and subclinical malabsorption among residents of tropical areas where sprue is endemic represent different manifestations, in terms of clinical presentation and pathological severity, of the same disease process of which overt tropical sprue represents the clinically recognisable "tip of the iceberg". Perhaps there should be a statute of limitations for any such hypothesis; after a decade it should be reconsidered in light of the information available when it was first put forward, re-examined in terms of subsequently acquired facts, and then be reaffirmed, modified, or discarded. In 1967 information on subclinical malabsorption was confined to that from two tropical countries, South India and Haiti, both of which are endemic for sprue.34 In these areas adults showed a spectrum in the severity of symptoms, intestinal abnormalities, and nutritional deficiencies, varying from mild to moderate among relatively symptom-free persons to severe in overt sprue. It seemed reasonable at that time to conjecture that these abnormalities represent varied manifestations of the same disease process. This concept was supported by a failure to identify, by light or electron microscopy, any basic difference between the intestinal structural abnormalities in sprue and subclinical malabsorption,S and by the observation that treatment with folic acid and/or tetracycline improved the intestinal lesion in persons recognised to have sprue and in some with subclinical malabsorption.6 It now seems, however, that sprue and subclinical malabsorption represent different clinical entities in many instances. Subclinical intestinal abnormalities have now been described among residents of areas such as those described by Perea et al. where sprue does not occur and, in this circumstance, they clearly are unrelated to sprue. Such is undoubtedly also the case in many instances in areas where sprue is endemic, particularly in children among whom sprue is rare. The distinction remains less clear in some adults, however, due in large part to our inability to define precisely what constitutes tropical sprue. In 1971, Baker and I advocated that the rigid criteria for the diagnosis of sprue, such as megaloblastic anaemia, should be modified and that this disorder should be considered as a syndrome which is characterised by structural abnormalities and malabsorption of two distinct substances.7 This definition, which would encompass from 11 % of the population in Puerto Rico to 43% in Haiti,s requires further modification. Firstly, it fails to take into consideration the fact that in sprue symptoms (if present) and intestinal abnormalities get relentlessly worse until specific therapy is instituted, whereas the picture in subclinical malabsorption seems to vary only slightly over time, either improving or worsening.8 9 Secondly, although subclinical malabsorption may contribute to nutritional deficiencies where dietary intake is marginal or inadequate8 it is rarely severe enough to produce the multiple, severe nutritional deficiences characteristic of advanced sprue. Thirdly, the key role of folate or vitamin-B12 deficiency, which
logical
D., Fernan-Zegarra, L., Cruz, V. M., Ballon, R., Picoaga, J. L. Lancet, 1978, ii, 550. 2. Klipstein, F. A. Ann. intern. Med. 1967, 66, 622. 3. Baker, S. J. Indian J. med. Sci. 1957, 11, 687. 4. Klipstein, F. A., Samloff, I. M., Schenk, E. A. Ann. intern. Med. 1966, 64, 1. Perea, V.
575. 5. Brunser, O., Eidelman, S., Klipstein, F. A. Gastroenterology, 1970, 58, 655. 6. Klipstein, F. A., Samloff, I. M., Smarth, G., Schenk, E. A. Gut, 1969, 10, 315. 7. Klipstein, F. A., Baker, S. J. Gastroenterology, 1970, 58, 717. 8. Klipstein, F. A. in Gastroenterology, vol. ii (edited by H. L. Bockus); p. 285.
Philadelphia, 1976. 9. Lindenbaum, J., Jamiul Alam, A. K. M., Kent, T. H. Br. med. J. 1966, ii, 1616.