- Email: [email protected]
IMMUNE COMPLEX AND MITE ANTIGEN IN KAWASAKI DISEASE
980 DIETARY FIBRE AND SURVIVAL
SIR,-The Zutphen population (Sept. 4,
p. 518) on average ate a head is about diet. Their daily mean intake of 31 50% greater than the mean for a U.K. population and is similar to that of some groups of vegetarians2 The mean amount ingested daily by the Zutphen high consuming quintile (37 g) is probably similar to that ingested in the past.2A century or more ago,3 bread consumption (mainly less refined) was 3-4 times greater than a recent estimate of about 150 g per day;4 moreover, porridge was widely consumed, as were potatoes. Nowadays, to raise dietary fibre intakes meaningfully would (as many have stressed) require much more than simply replacing white by brown bread or the daily ingestion ofa couple of tablespoonsful of bran. In Switzerland in the 1939-45 war the daily diet included an average of 370 g bread (90% extraction rate) and potatoes (500 g) and vegetables (400 g) were double peace-time consumptions. Such intakes, with increased consumptions of fresh and dried fruit, must have afforded most people 30-40 g fibre per5 day. Reports testified to the improved health of the population.5 In Third World populations, with rises in literacy and economic circumstances, the carbohydrate moiety of the diet tends to fall, especially with urbanisation. Bread consumption is in part replacing that of staple cereals such as maize. In South Africa most rural Blacks still ingest large amounts of fibre (30-40 g daily). The tendency for this consumption to decrease is offset by the large price differential-a 900 g loaf of brown bread costs 35 cents (about 171f2 p) while white bread costs 52 cents (26 p). This policy is so effective that most country stores sell brown bread only. At 50 years of age a South African Black stands a better chance than a White of reaching the age of 70.6 Blacks, even in urban areas, experience very little coronary heart disease and non-infective bowel diseases, including colon cancer.7 While the messages from Zutphen and other studies and the recommendations of dietary goals are plausible the chances of a meaningful rise in fibre intake seem remote, though the situation could soon change. In the worldwide scene restrictions in the production of animal food products, to allow greater production and consumption of higher yielding plant products will be dictated by economy of land usage and the increased numbers of non-Western mouths that will have to be fed. This view is appreciated: "At present Britain gives two thirds of its grain to livestock ... Our farmland is productive enough to support 250 million people on a
high-fibre
per
8
vegetarian diet".
high
Johannesburg 2001, South Africa Baragwanath Hospital, Johannesburg
A. R. P. WALKER I. SEGAL
Department of Nutrition, University of Durban-Westville
S. HATHORN
JSS, et al. Symptomless diverticular disease and intake of dietary fibre. Lancet 1979; i: 511-14. Bingham S, et al. Intakes and sources of dietary fibre in the British population. Am J Clin Nutr 1979; 32: 1313-19. Editorial. Brown bread versus white. Br Med J 1937; ii: 752-53.
1. Gear 2.
SIR,-When I dared to complain to the BM that an editorial2 entitled Eating and Ulcers merely demolished classic sloppy ulcer diets and ignored the possible value of the high-fibre regimen,3I was admonished and asked for data that "thick chapattis, thick dhal, vegetable curries, and yoghurt or even just unprocessed bran, will work in the West". I was naturally delighted to see my proposal tested in a Western country, Norway, and apparently confirmed. Dr Rydning and colleagues (Oct. 2, p. 736) found 28 (80%) relapses of 35 patients put on a low-fibre diet (0-18, median 11 g/day), significantly less than the 17 (45%) relapsed of 38 patients given a high-fibre diet (9-47, median 28 g/day). Nevertheless their claim that "A diet rich in fibre may, therefore protect against duodenal ulceration" may not be strictly valid, and I suggest an alternative hypothesis. Although Rydning et al. state "there was no clear dose response relationship" their data can be retabulated, for simplicity in
integers:
Thus patients given a higher than normal fibre diet, whether quite high or very high, had an almost identical relapse rate (half) to that in patients on a low-fibre diet who barely reduced their fibre. What seems to me to have happened is that the patients who reduced their fibre drastically increased their relapse rate to almost 100% (14/15). Thus a low-fibre diet may predispose to relapse of duodenal ulcer, both in India and Norway, but adding fibre to a European’s normal moderate fibre diet may not decrease the rate of recurrence. One analogy would be zinc treatment of leg ulcers which speeded healing in patients who were zinc deficient but not in those with normal serum
zinc.44
Department of Surgery, Royal Postgraduate School, Hammersmith Hospital, London W12 0HS
In the meantime it is imperative that as much as possible be learnt of the experience of groups, such as the upper quintile of the fibre intake. To Zutphen population, now habituated to a tackle an analogous problem-the bearing of fat intake on cancer-Enstrom9 has urged that the life experience of the very-lowfat-consuming moiety of American women be studied prospectively. Such studies are in line with Ryle’slO belief that research on the unfit should really be matched in scope and intensity by research on the fit. South African Institute for Medical Research,
HIGH FIBRE GOOD OR LOW FIBRE BAD FOR DUODENAL ULCERS?
3. 4. National Food Survey Committee. Household food consumption and expenditure, 1975. London: HMSO, 1977. 5 Fleish A. Nutrition in Switzerland during the war. Schweiz Med Wochnschr 1946; 76:
889-93 6. Walker ARP. Survival rate at middle-age in developing and western populations. Postgrad Med J 1974; 50: 29-32. 7. Walker ARP, Segal I. Epidemiology of non-infective intestinal diseases in various ethnic groups in South Africa. Israel J Med Sci 1979; 15: 309-13 8. Editorial. Sensible eating. Br Med J 1977; ii: 80. 9. Enstrom JE. Re-assessment of the role the dietary fat in cancer etiology. Cancer Res 1981; 41: 3722-23. 10. Ryle JA. Social medicine: Its meaning and scope. Br Med 1943; ii: 633-36. J
J. H. BARON
IMMUNE COMPLEX AND MITE ANTIGEN IN KAWASAKI DISEASE
SIR,-In 1981 Furusho et all suggested that the mite antigen may have a causative role in Kawasaki disease. Now, Dr Hamashima and colleagues (July 31, p.266) describe electron microscopic evidence for rickettsia-like particles in the mite which are similar to those found in skin biopsy specimens of patients with Kawasaki disease. We have studied the immune complexes in Kawasaki disease. IgG circulating immune complex (CIC) was detected in 50 of 67 cases (75%) by Raji cell assay with fluorescein isothiocyanate (FITC) conjugated anti-human IgG rabbit serum. By about the 30th day of illness CIC titres reached a plateau before decreasing. By Clq enzyme immune assay CICs were detected in 11 of 36 cases (31%). IgM CIC was detected in 18 of 26 cases (70%), and these complexes appeared earlier and decreased sooner than did IgG CIC. Rabbits were immunised with the mite antigen (Torii) from Dermatophagoides farinae. The antigen moiety of the IC and the presence of the antigen in biopsy specimens were detected by indirect immunofluorescence with anti-mite rabbit serum which 1. Baron JH. Eating and ulcers. Br Med J 1980; 280: 795. 2. Editorial. Eating and ulcers. Br Med J 1980; 280: 205-06. 3. Malhotra SL. A comparison of unrefined wheat and rice diet in the management of duodenal ulcer. Postgrad MedJ 1978; 54: 6-9. 4. Hallbook T, Lanner E. Serum-zinc and healing of venous leg ulcers. Lancet 1972; ii: 780-82. 5. Furusho K, Ohba T, Eda T, et al. Possible role for mite antigen in Kawasaki disease. Lancet 1981; ii: 194.
981 cuticles and mite organs were stained by sera from patients with bronchial asthma. These results suggest that IC may play a role in the inflammatory process and that the mite may have some aetiological role in Kawasaki disease. Furusho et al. speculated on mite allergy as the causative mechanism. However, the high titres of IgM CIC that we found in the early stages of the illness, the subsequently increased IgG CIC, and the lack of positive immunofluorescent stain with patient’s sera in mite cuticles and bodies of dead mites suggest Kawasaki disease is not due to allergy to mites, but is associated with infection of the mites with some microorganisms. T. FUJIMOTO H. KATO E. ICHIOSE Y. SASAGURI
Departments of Paediatrics and Pathology, Kurume University School of Medicine, Kurume 830, Japan
TRH AND SPINOCEREBELLAR DEGENERATION MMMMENNEW
Fig. 1-Cervical lymph node biopsy specimen of 6-year-old patient on the llth day of the third
recurrence
of Kawasaki disease.
Immunofluorescent stain with FITC anti-rabbit gamma-globulin goat incubated with anti-mite rabbit serum (x40). Numerous fluorescent foci of mite antigen are seen in polymorphonuclear cells, with depositions of IgG in the same portion. serum
Fig. 2-Cross-section patient) (x 70).
of D.
pteronyssinus (house
dust mite from
a
Immunofluorescent stain with FITC rabbit anti-human IgG serum incubated with convalescent sera from patient with Kawasaki disease. Shows IgG antibody to mite antigen in various organs, except cuticle.
had high titres of anti-mite IgG antibody (2600 mg/dl). Using Raji cell assay with FITC conjugated anti-rabbit IgG goat serum incubated with anti-mite rabbit serum, we found that the CIC for 28 of 38 cases (74%) was positive for mite antigen. The pericardial effusion, synovial fluid, and vesicular fluid in blisters in 14 patients with Kawasaki disease had higher titres in comparison with paired sera, and mite antigen in exudates was detected in 4 of 7 cases. We found deposition of each immunoglobulin class antibody in all 14 biopsy specimens and the mite antigen was detected in 12 of those specimens. As controls, and using the same method, we examined the same specimens with anti-mite serum absorbed by mite antigen or with unimmunised rabbit serum. The results were all negative, which suggested that our findings might be specific. In other diseases, such as juvenile rheumatoid arthritis or systemic lupus erythematosus, no mite antigen was detected in CIC. In the mesenteric lymph node obtained from a patient with benign abdominal tumour and in the pelvic lymph node of a patient with a uterine myoma neither antibody nor mite antigen was demonstrated. We examined the localisation of the mite antigen in the mite crosssections using an indirect immunofluorescent stain with convalescent sera of the patients. The mite organs (mainly salivary coxal, and genital glands) but not the cuticles of the mite D. pteronyssanus in dust from the patient’s home were stained significantly with sera from three patients. In contrast, both mite
SiR,-A letter in The Lancet in 19806 discussed symptomatic therapy of spinocerebellar degeneration with thyrotropin-releasing hormone (TRH). Because TRH produced improved coordination in an ataxic mouse strainSobue and colleagues gave this hormone to several hundred patients affected with cerebellar disorders. This large collaborative study in Japan concluded9 that some patients, after as little as 0 -5mg of parenteral TRH, experienced transient improvement of cerebellar signs or symptoms. The responses were idiosyncratic and tended to occur in more mildly affected patients; improvement was, in some instances,6 substantiated by measurements of extraocular movements and balance. Delayed, cumulative, or dose-related benefits were not reported among the responders. We have done a trial of intravenous TRH in 13 patients with mild to severe disability from a variety of progressive degenerative cerebellar disorders. Symptoms included incoordination, dysmetria, ataxic speech, gait disturbance, and tremor. The diagnoses included idiopathic cerebellar dysfunction without atrophy or other neurological signs (7 patients); multisystem degeneration 10 (cerebellar, pyramidal, and extrapyramidal dysfunction, 3 patients); Friedreich ataxia (2 patients), and Kallman syndrome" (1 patient). Patients were given active placebo (nicotinic acid) or TRH (1-6’5 mg), and cerebellar function was assessed frequently thereafter. Only 1 of the patients manifested an objective response from TRH, with unequivocal improvement of handwriting, and mild improvement in dysarthria and gait on one occasion. Subsequent testing, however, failed to substantiate these benefits. On all occasions, the testing was free of significant sideeffects ; facial flushing and an urge for micturition were common experiences. TRH has been administered intravenously in a dose of 20 mg without adverse symptoms. 12 The lack of benefit from single-dose parenteral TRH in our study contrasts with the Japanese collaborative More long-term trials of TRH therapy and the use of more potent analogues13 may help to assess the potential for the use of this neuropeptide in cerebellar disorders and other applications.
study.6,8,9
Experimental Therapeutics Branch, N.I.N.C.D.S., National Institutes of Health, Bethesda, Maryland 20205, U.S.A.
PETER A. LEWITT
JOEL R. L. EHRENKRANZ
Konagaya M, et al. Effect of thyrotropin-releasing hormone on of spinocerebellar degeneration. Lancet 1980; i: 418-19. Adachi K, Konagaya M, Muroga T, et al. Effects of thyrotropin-releasing hormone on ataxia of rolling mouse Nagoya. Igaku no Ayumi 1977, 101: 74-75 Sobue I, Muroga T, Konagaya M, et al Effects of thyrotropin-releasing hormone on ataxia in spinocerebellar degenerations. In Sobue I, ed. Spinocerebellar degenerations. Tokyo: University of Tokyo Press, 1980: 83-94. Sobue I. Study of oral and injected therapy with protirelin tartrate (TRH-T) for the ataxia in spinocerebellar degenerations (SCD) In: Annual reports of Spinocerebellar Degeneration Research Committee, Japan, 1979: 55-68. Hirayama K. Analysis of clinical features in cerebello-extrapyramidal system degeneration. In Sobue I, ed. Spinocerebellar degenerations Tokyo- University of Tokyo Press, 1980: 83-94. Nutting PA, Schimke RN The Kallman syndrome. In: Bergsma D, ed. The clinical delineation of birth defects: Part X (Birth Defects Orig Art Ser Vol VII, no 6).
6. Sobue I, Yamamoto H,
ataxia
7. 8.
9.
10
11.
-
Baltimore: Williams and Wilkins, 1971: 172-74. TN, Woods AC, Lipton MA, Morris CE. Hypothalamic releasing factors and Parkinson’s disease. Arch Neurol 1974, 31: 55-56. 13. Yarbrough GG. On the neuropharmacology of thyrotropin releasing hormone (TRH).
12. Chase
Prog Neurobiol 1979;
12: 291-312.
SIR,-The Zutphen population (Sept. 4,
p. 518) on average ate a head is about diet. Their daily mean intake of 31 50% greater than the mean for a U.K. population and is similar to that of some groups of vegetarians2 The mean amount ingested daily by the Zutphen high consuming quintile (37 g) is probably similar to that ingested in the past.2A century or more ago,3 bread consumption (mainly less refined) was 3-4 times greater than a recent estimate of about 150 g per day;4 moreover, porridge was widely consumed, as were potatoes. Nowadays, to raise dietary fibre intakes meaningfully would (as many have stressed) require much more than simply replacing white by brown bread or the daily ingestion ofa couple of tablespoonsful of bran. In Switzerland in the 1939-45 war the daily diet included an average of 370 g bread (90% extraction rate) and potatoes (500 g) and vegetables (400 g) were double peace-time consumptions. Such intakes, with increased consumptions of fresh and dried fruit, must have afforded most people 30-40 g fibre per5 day. Reports testified to the improved health of the population.5 In Third World populations, with rises in literacy and economic circumstances, the carbohydrate moiety of the diet tends to fall, especially with urbanisation. Bread consumption is in part replacing that of staple cereals such as maize. In South Africa most rural Blacks still ingest large amounts of fibre (30-40 g daily). The tendency for this consumption to decrease is offset by the large price differential-a 900 g loaf of brown bread costs 35 cents (about 171f2 p) while white bread costs 52 cents (26 p). This policy is so effective that most country stores sell brown bread only. At 50 years of age a South African Black stands a better chance than a White of reaching the age of 70.6 Blacks, even in urban areas, experience very little coronary heart disease and non-infective bowel diseases, including colon cancer.7 While the messages from Zutphen and other studies and the recommendations of dietary goals are plausible the chances of a meaningful rise in fibre intake seem remote, though the situation could soon change. In the worldwide scene restrictions in the production of animal food products, to allow greater production and consumption of higher yielding plant products will be dictated by economy of land usage and the increased numbers of non-Western mouths that will have to be fed. This view is appreciated: "At present Britain gives two thirds of its grain to livestock ... Our farmland is productive enough to support 250 million people on a
high-fibre
per
8
vegetarian diet".
high
Johannesburg 2001, South Africa Baragwanath Hospital, Johannesburg
A. R. P. WALKER I. SEGAL
Department of Nutrition, University of Durban-Westville
S. HATHORN
JSS, et al. Symptomless diverticular disease and intake of dietary fibre. Lancet 1979; i: 511-14. Bingham S, et al. Intakes and sources of dietary fibre in the British population. Am J Clin Nutr 1979; 32: 1313-19. Editorial. Brown bread versus white. Br Med J 1937; ii: 752-53.
1. Gear 2.
SIR,-When I dared to complain to the BM that an editorial2 entitled Eating and Ulcers merely demolished classic sloppy ulcer diets and ignored the possible value of the high-fibre regimen,3I was admonished and asked for data that "thick chapattis, thick dhal, vegetable curries, and yoghurt or even just unprocessed bran, will work in the West". I was naturally delighted to see my proposal tested in a Western country, Norway, and apparently confirmed. Dr Rydning and colleagues (Oct. 2, p. 736) found 28 (80%) relapses of 35 patients put on a low-fibre diet (0-18, median 11 g/day), significantly less than the 17 (45%) relapsed of 38 patients given a high-fibre diet (9-47, median 28 g/day). Nevertheless their claim that "A diet rich in fibre may, therefore protect against duodenal ulceration" may not be strictly valid, and I suggest an alternative hypothesis. Although Rydning et al. state "there was no clear dose response relationship" their data can be retabulated, for simplicity in
integers:
Thus patients given a higher than normal fibre diet, whether quite high or very high, had an almost identical relapse rate (half) to that in patients on a low-fibre diet who barely reduced their fibre. What seems to me to have happened is that the patients who reduced their fibre drastically increased their relapse rate to almost 100% (14/15). Thus a low-fibre diet may predispose to relapse of duodenal ulcer, both in India and Norway, but adding fibre to a European’s normal moderate fibre diet may not decrease the rate of recurrence. One analogy would be zinc treatment of leg ulcers which speeded healing in patients who were zinc deficient but not in those with normal serum
zinc.44
Department of Surgery, Royal Postgraduate School, Hammersmith Hospital, London W12 0HS
In the meantime it is imperative that as much as possible be learnt of the experience of groups, such as the upper quintile of the fibre intake. To Zutphen population, now habituated to a tackle an analogous problem-the bearing of fat intake on cancer-Enstrom9 has urged that the life experience of the very-lowfat-consuming moiety of American women be studied prospectively. Such studies are in line with Ryle’slO belief that research on the unfit should really be matched in scope and intensity by research on the fit. South African Institute for Medical Research,
HIGH FIBRE GOOD OR LOW FIBRE BAD FOR DUODENAL ULCERS?
3. 4. National Food Survey Committee. Household food consumption and expenditure, 1975. London: HMSO, 1977. 5 Fleish A. Nutrition in Switzerland during the war. Schweiz Med Wochnschr 1946; 76:
889-93 6. Walker ARP. Survival rate at middle-age in developing and western populations. Postgrad Med J 1974; 50: 29-32. 7. Walker ARP, Segal I. Epidemiology of non-infective intestinal diseases in various ethnic groups in South Africa. Israel J Med Sci 1979; 15: 309-13 8. Editorial. Sensible eating. Br Med J 1977; ii: 80. 9. Enstrom JE. Re-assessment of the role the dietary fat in cancer etiology. Cancer Res 1981; 41: 3722-23. 10. Ryle JA. Social medicine: Its meaning and scope. Br Med 1943; ii: 633-36. J
J. H. BARON
IMMUNE COMPLEX AND MITE ANTIGEN IN KAWASAKI DISEASE
SIR,-In 1981 Furusho et all suggested that the mite antigen may have a causative role in Kawasaki disease. Now, Dr Hamashima and colleagues (July 31, p.266) describe electron microscopic evidence for rickettsia-like particles in the mite which are similar to those found in skin biopsy specimens of patients with Kawasaki disease. We have studied the immune complexes in Kawasaki disease. IgG circulating immune complex (CIC) was detected in 50 of 67 cases (75%) by Raji cell assay with fluorescein isothiocyanate (FITC) conjugated anti-human IgG rabbit serum. By about the 30th day of illness CIC titres reached a plateau before decreasing. By Clq enzyme immune assay CICs were detected in 11 of 36 cases (31%). IgM CIC was detected in 18 of 26 cases (70%), and these complexes appeared earlier and decreased sooner than did IgG CIC. Rabbits were immunised with the mite antigen (Torii) from Dermatophagoides farinae. The antigen moiety of the IC and the presence of the antigen in biopsy specimens were detected by indirect immunofluorescence with anti-mite rabbit serum which 1. Baron JH. Eating and ulcers. Br Med J 1980; 280: 795. 2. Editorial. Eating and ulcers. Br Med J 1980; 280: 205-06. 3. Malhotra SL. A comparison of unrefined wheat and rice diet in the management of duodenal ulcer. Postgrad MedJ 1978; 54: 6-9. 4. Hallbook T, Lanner E. Serum-zinc and healing of venous leg ulcers. Lancet 1972; ii: 780-82. 5. Furusho K, Ohba T, Eda T, et al. Possible role for mite antigen in Kawasaki disease. Lancet 1981; ii: 194.
981 cuticles and mite organs were stained by sera from patients with bronchial asthma. These results suggest that IC may play a role in the inflammatory process and that the mite may have some aetiological role in Kawasaki disease. Furusho et al. speculated on mite allergy as the causative mechanism. However, the high titres of IgM CIC that we found in the early stages of the illness, the subsequently increased IgG CIC, and the lack of positive immunofluorescent stain with patient’s sera in mite cuticles and bodies of dead mites suggest Kawasaki disease is not due to allergy to mites, but is associated with infection of the mites with some microorganisms. T. FUJIMOTO H. KATO E. ICHIOSE Y. SASAGURI
Departments of Paediatrics and Pathology, Kurume University School of Medicine, Kurume 830, Japan
TRH AND SPINOCEREBELLAR DEGENERATION MMMMENNEW
Fig. 1-Cervical lymph node biopsy specimen of 6-year-old patient on the llth day of the third
recurrence
of Kawasaki disease.
Immunofluorescent stain with FITC anti-rabbit gamma-globulin goat incubated with anti-mite rabbit serum (x40). Numerous fluorescent foci of mite antigen are seen in polymorphonuclear cells, with depositions of IgG in the same portion. serum
Fig. 2-Cross-section patient) (x 70).
of D.
pteronyssinus (house
dust mite from
a
Immunofluorescent stain with FITC rabbit anti-human IgG serum incubated with convalescent sera from patient with Kawasaki disease. Shows IgG antibody to mite antigen in various organs, except cuticle.
had high titres of anti-mite IgG antibody (2600 mg/dl). Using Raji cell assay with FITC conjugated anti-rabbit IgG goat serum incubated with anti-mite rabbit serum, we found that the CIC for 28 of 38 cases (74%) was positive for mite antigen. The pericardial effusion, synovial fluid, and vesicular fluid in blisters in 14 patients with Kawasaki disease had higher titres in comparison with paired sera, and mite antigen in exudates was detected in 4 of 7 cases. We found deposition of each immunoglobulin class antibody in all 14 biopsy specimens and the mite antigen was detected in 12 of those specimens. As controls, and using the same method, we examined the same specimens with anti-mite serum absorbed by mite antigen or with unimmunised rabbit serum. The results were all negative, which suggested that our findings might be specific. In other diseases, such as juvenile rheumatoid arthritis or systemic lupus erythematosus, no mite antigen was detected in CIC. In the mesenteric lymph node obtained from a patient with benign abdominal tumour and in the pelvic lymph node of a patient with a uterine myoma neither antibody nor mite antigen was demonstrated. We examined the localisation of the mite antigen in the mite crosssections using an indirect immunofluorescent stain with convalescent sera of the patients. The mite organs (mainly salivary coxal, and genital glands) but not the cuticles of the mite D. pteronyssanus in dust from the patient’s home were stained significantly with sera from three patients. In contrast, both mite
SiR,-A letter in The Lancet in 19806 discussed symptomatic therapy of spinocerebellar degeneration with thyrotropin-releasing hormone (TRH). Because TRH produced improved coordination in an ataxic mouse strainSobue and colleagues gave this hormone to several hundred patients affected with cerebellar disorders. This large collaborative study in Japan concluded9 that some patients, after as little as 0 -5mg of parenteral TRH, experienced transient improvement of cerebellar signs or symptoms. The responses were idiosyncratic and tended to occur in more mildly affected patients; improvement was, in some instances,6 substantiated by measurements of extraocular movements and balance. Delayed, cumulative, or dose-related benefits were not reported among the responders. We have done a trial of intravenous TRH in 13 patients with mild to severe disability from a variety of progressive degenerative cerebellar disorders. Symptoms included incoordination, dysmetria, ataxic speech, gait disturbance, and tremor. The diagnoses included idiopathic cerebellar dysfunction without atrophy or other neurological signs (7 patients); multisystem degeneration 10 (cerebellar, pyramidal, and extrapyramidal dysfunction, 3 patients); Friedreich ataxia (2 patients), and Kallman syndrome" (1 patient). Patients were given active placebo (nicotinic acid) or TRH (1-6’5 mg), and cerebellar function was assessed frequently thereafter. Only 1 of the patients manifested an objective response from TRH, with unequivocal improvement of handwriting, and mild improvement in dysarthria and gait on one occasion. Subsequent testing, however, failed to substantiate these benefits. On all occasions, the testing was free of significant sideeffects ; facial flushing and an urge for micturition were common experiences. TRH has been administered intravenously in a dose of 20 mg without adverse symptoms. 12 The lack of benefit from single-dose parenteral TRH in our study contrasts with the Japanese collaborative More long-term trials of TRH therapy and the use of more potent analogues13 may help to assess the potential for the use of this neuropeptide in cerebellar disorders and other applications.
study.6,8,9
Experimental Therapeutics Branch, N.I.N.C.D.S., National Institutes of Health, Bethesda, Maryland 20205, U.S.A.
PETER A. LEWITT
JOEL R. L. EHRENKRANZ
Konagaya M, et al. Effect of thyrotropin-releasing hormone on of spinocerebellar degeneration. Lancet 1980; i: 418-19. Adachi K, Konagaya M, Muroga T, et al. Effects of thyrotropin-releasing hormone on ataxia of rolling mouse Nagoya. Igaku no Ayumi 1977, 101: 74-75 Sobue I, Muroga T, Konagaya M, et al Effects of thyrotropin-releasing hormone on ataxia in spinocerebellar degenerations. In Sobue I, ed. Spinocerebellar degenerations. Tokyo: University of Tokyo Press, 1980: 83-94. Sobue I. Study of oral and injected therapy with protirelin tartrate (TRH-T) for the ataxia in spinocerebellar degenerations (SCD) In: Annual reports of Spinocerebellar Degeneration Research Committee, Japan, 1979: 55-68. Hirayama K. Analysis of clinical features in cerebello-extrapyramidal system degeneration. In Sobue I, ed. Spinocerebellar degenerations Tokyo- University of Tokyo Press, 1980: 83-94. Nutting PA, Schimke RN The Kallman syndrome. In: Bergsma D, ed. The clinical delineation of birth defects: Part X (Birth Defects Orig Art Ser Vol VII, no 6).
6. Sobue I, Yamamoto H,
ataxia
7. 8.
9.
10
11.
-
Baltimore: Williams and Wilkins, 1971: 172-74. TN, Woods AC, Lipton MA, Morris CE. Hypothalamic releasing factors and Parkinson’s disease. Arch Neurol 1974, 31: 55-56. 13. Yarbrough GG. On the neuropharmacology of thyrotropin releasing hormone (TRH).
12. Chase
Prog Neurobiol 1979;
12: 291-312.