111
LABORATORY DATA FOR PATIENTS WITH ENDEMIC CRETINISM
Rapid transition from methadone maintenance to naltrexone SIR,-Dr Brewer and Dr Mathew (Sept 16,
p
683) combine
clonidine and naltrexone for rapid induction to naltrexone maintenance, but report severe side-effects and do not discuss clean urine samples as a criterion for successful detoxification treatment. We have described a humane and effective method of detoxification, with the drawback that trained staff and complex technical equipment are needed.l,2 To produce a safe, rapid, successful, painless, and economic alternative treatment we used midazolam, a short-acting benzodiazepine, to suppress the naloxone "flush" seen in opiate addicts; the midazolam action is then reversed by flumazenil. Twelve hours after the last oral methadone intake, 7 opiate-dependent patients were sedated by a bolus of 30 mg midazolam given into a peripheral vein; 4 mg naloxone diluted with 200 ml saline 0-9% was then injected within 10 min by means of a motor-pump. To suppress any physical effects during naloxone administration, the patients received repeated injections of midazolam (50-75 mg). Shortly after completion of infusion treatment, patients received repeated doses of flumazenil (2-6 mg) until fully awake. The opiate antagonist maintenance treatment was continued with oral naltrexone (50 mg). This dose was repeated every 24 h until opiates were not detected in urine samples. The onset of withdrawal signs and symptoms following naloxone was completely suppressed by midazolam. After flumazenil was stopped withdrawal signs and symptoms could not be detected with the Wang-rating scale. Oral administration of naltrexone suppressed further withdrawal symptoms after the effects of naloxone had worn off. Heart rate, blood pressure, body temperature, body weight, and respiratory rate remained stable during treatment. Furthermore, no changes in routine laboratory blood tests could be observed in any patient. Before discharge, all urine samples were negative for opioids and benzodiazepines. Benzodiazepines were not found at least 48 h after midazolam was given. Patients on methadone were observed until 120 h after the last intake. All 7 patients completed detoxification treatment successfully. This rapid and safe approach allows the fast reduction of detoxification without danger to the patient. Department of Psychiatry and First Department of Internal Medicine, University of Vienna, A-1090 Vienna, Austria
NORBERT LOIMER KURT LENZ OTTO PRESSLICH RAINER SCHMID
N, Schmid R, Presslich O, Lenz K. Naloxone treatment for opiate withdrawal syndrome. Br J Psychiatry 1988, 153: 851-52. 2. Loimer N, Schmid RW, Presslich O, Lenz K. Continuous naloxone administration suppresses opiate withdrawal symptoms in human opiate addicts during detoxification treatment. J Psychiatr Res 1989; 23: 81-86. 3. Sage DJ, Close A, Boas RA. Reversal of midazolam sedation with Anexate. Br J 1. Loimer
Anaesth 1987; 59: 459-64.
Thyroid autoimmunity and endemic cretinism SIR,-Dr Boyages and colleagues (Sept 2, p 529) suggest a possible role for thyroid autoimmunity in endemic cretinism in the Qinghai Province in China. We report a similar blocking effect of IgGs in patients with endemic cretinism. We have studied 8 such patients from the Balsas region, State of Maranhao, in northern Brazil (table). Apart from 1 patient with a multinodular goitre (about 90 g) all had thyroid atrophy or barely palpable thyroid glands. In this region 85 % of all inhabitants have a
goitre grade I or larger (World Health Organisation classification) because of chronic iodine deficiency. IgG was extracted from sera and purified
by diethylaminoethyl-column chromatography. For
growth experiments FRTL-5 cells
were transferred to 24-well maintained in hormone-free medium containing 5% fetal calf serum for 5-10 days. Cells were washed twice with hormone-free medium containing 0’ 1 % bovine serum albumin (BSA) then incubated with 500 pl of growth-assay medium containing 2 mg/ml IgG with 10-10 mol/l thyrotropin
plates by trypsinisation, and
were
’TSH) (thyroid growth inhibiting immunoglobulin assay)
or
*% inhibition of FRTL-5 cells growth
by patients’ IgG
NI
=
no
mhlbitlon
without IgG (TSH stimulation control). After 42 h incubation, medium was aspirated and replaced with 250 III of RPMI 1640 medium with methyl 3H-thymidine (18-5 x 104 Bq/ml) and counted. Thyroglobulin II (TGII) was expressed as percentage inhibition and was compared with that achieved with medium and TSH. Sera obtained from 11 non-goitrous healthy individuals (hospital staff) were controls, and TSH inhibition of growth ranged from none to 13%. By contrast the TSH-induced cell growth was inhibited to 16-87% of control values by 2 mg of IgGs extracted from patients with endemic cretinism (table). None of these patients had a positive test for antibodies to thyroid microsomes, thyroglobulin, or TSH. As shown in the table the only patient (C 17) whose serum did not have an inhibitory effect on cell growth had goitrous cretinism. The immunogenic inhibition of thyroid cells in culture would explain the fact that most of these individuals have either thyroid atrophy or very small glands, as well as chronic iodine deficiency. Our data are in accord with Boyages and colleagues’ hypothesis that immunological factors leading to thyroid destruction or inhibition of thyroid regeneration are important in the pathogenesis of myxoedematous cretinism. Thyroid Laboratory, Division of Endocrinology, Hospital das Clinicas, Faculty of Medicine, University of São Paulo, São Paulo, Brazil
Serum
GERALDO MEDEIROS-NETO KUMIKO TSUBOI NICOLAU LIMA
25-hydroxyvitamin D and colon cancer
SIR,-Dr Garland and colleagues’ study (Nov 18, p 1176) showing that high concentrations of serum 25-hydroxyvitamin D (25-OHD) are associated with reduced colon cancer risk is of considerable importance. As Garland et al point out, colon cancer mortality is highest in areas of the world with little sunshine. Agricultural methods in these temperate areas produce an abundance of meat and fat (associated with high colon-cancer risk) for the western diet whereas cereal and vegetarian-based diets (associated with low colon-cancer risk) prevail in lower latitudes, where there is much sunshine. The correlation of high sunshine exposure with dietary practices associated with low colon-cancer rates now suggests that the protection conferred by such diets may be at least partly attributable to the confounding variable of high sunshine exposure. Even in northern latitudes vegetarianism is frequently associated with "healthy" life-styles that include the consumption of vitamins and high outdoor exposure. The colon-cancer experience in the British Asians is therefore instructive. The frequency of this cancer in this population is low and much the same as that in the Indian subcontinent.2 An Asian population of about 15 000 has been established in Glasgow (latitude 55°52’ north) and the west of Scotland for over thirty years. Between 1961 and 1981 the west of Scotland cancer registry recorded only 2 cases of colon cancer in Asian patients aged 45-64 years against 14-2 cases expected (p < 0’05) on the basis of indigenous population rates.3 The British Asian population also constitutes the largest reservoir of endemic vitamin D deficiency in
LABORATORY DATA FOR PATIENTS WITH ENDEMIC CRETINISM
Rapid transition from methadone maintenance to naltrexone SIR,-Dr Brewer and Dr Mathew (Sept 16,
p
683) combine
clonidine and naltrexone for rapid induction to naltrexone maintenance, but report severe side-effects and do not discuss clean urine samples as a criterion for successful detoxification treatment. We have described a humane and effective method of detoxification, with the drawback that trained staff and complex technical equipment are needed.l,2 To produce a safe, rapid, successful, painless, and economic alternative treatment we used midazolam, a short-acting benzodiazepine, to suppress the naloxone "flush" seen in opiate addicts; the midazolam action is then reversed by flumazenil. Twelve hours after the last oral methadone intake, 7 opiate-dependent patients were sedated by a bolus of 30 mg midazolam given into a peripheral vein; 4 mg naloxone diluted with 200 ml saline 0-9% was then injected within 10 min by means of a motor-pump. To suppress any physical effects during naloxone administration, the patients received repeated injections of midazolam (50-75 mg). Shortly after completion of infusion treatment, patients received repeated doses of flumazenil (2-6 mg) until fully awake. The opiate antagonist maintenance treatment was continued with oral naltrexone (50 mg). This dose was repeated every 24 h until opiates were not detected in urine samples. The onset of withdrawal signs and symptoms following naloxone was completely suppressed by midazolam. After flumazenil was stopped withdrawal signs and symptoms could not be detected with the Wang-rating scale. Oral administration of naltrexone suppressed further withdrawal symptoms after the effects of naloxone had worn off. Heart rate, blood pressure, body temperature, body weight, and respiratory rate remained stable during treatment. Furthermore, no changes in routine laboratory blood tests could be observed in any patient. Before discharge, all urine samples were negative for opioids and benzodiazepines. Benzodiazepines were not found at least 48 h after midazolam was given. Patients on methadone were observed until 120 h after the last intake. All 7 patients completed detoxification treatment successfully. This rapid and safe approach allows the fast reduction of detoxification without danger to the patient. Department of Psychiatry and First Department of Internal Medicine, University of Vienna, A-1090 Vienna, Austria
NORBERT LOIMER KURT LENZ OTTO PRESSLICH RAINER SCHMID
N, Schmid R, Presslich O, Lenz K. Naloxone treatment for opiate withdrawal syndrome. Br J Psychiatry 1988, 153: 851-52. 2. Loimer N, Schmid RW, Presslich O, Lenz K. Continuous naloxone administration suppresses opiate withdrawal symptoms in human opiate addicts during detoxification treatment. J Psychiatr Res 1989; 23: 81-86. 3. Sage DJ, Close A, Boas RA. Reversal of midazolam sedation with Anexate. Br J 1. Loimer
Anaesth 1987; 59: 459-64.
Thyroid autoimmunity and endemic cretinism SIR,-Dr Boyages and colleagues (Sept 2, p 529) suggest a possible role for thyroid autoimmunity in endemic cretinism in the Qinghai Province in China. We report a similar blocking effect of IgGs in patients with endemic cretinism. We have studied 8 such patients from the Balsas region, State of Maranhao, in northern Brazil (table). Apart from 1 patient with a multinodular goitre (about 90 g) all had thyroid atrophy or barely palpable thyroid glands. In this region 85 % of all inhabitants have a
goitre grade I or larger (World Health Organisation classification) because of chronic iodine deficiency. IgG was extracted from sera and purified
by diethylaminoethyl-column chromatography. For
growth experiments FRTL-5 cells
were transferred to 24-well maintained in hormone-free medium containing 5% fetal calf serum for 5-10 days. Cells were washed twice with hormone-free medium containing 0’ 1 % bovine serum albumin (BSA) then incubated with 500 pl of growth-assay medium containing 2 mg/ml IgG with 10-10 mol/l thyrotropin
plates by trypsinisation, and
were
’TSH) (thyroid growth inhibiting immunoglobulin assay)
or
*% inhibition of FRTL-5 cells growth
by patients’ IgG
NI
=
no
mhlbitlon
without IgG (TSH stimulation control). After 42 h incubation, medium was aspirated and replaced with 250 III of RPMI 1640 medium with methyl 3H-thymidine (18-5 x 104 Bq/ml) and counted. Thyroglobulin II (TGII) was expressed as percentage inhibition and was compared with that achieved with medium and TSH. Sera obtained from 11 non-goitrous healthy individuals (hospital staff) were controls, and TSH inhibition of growth ranged from none to 13%. By contrast the TSH-induced cell growth was inhibited to 16-87% of control values by 2 mg of IgGs extracted from patients with endemic cretinism (table). None of these patients had a positive test for antibodies to thyroid microsomes, thyroglobulin, or TSH. As shown in the table the only patient (C 17) whose serum did not have an inhibitory effect on cell growth had goitrous cretinism. The immunogenic inhibition of thyroid cells in culture would explain the fact that most of these individuals have either thyroid atrophy or very small glands, as well as chronic iodine deficiency. Our data are in accord with Boyages and colleagues’ hypothesis that immunological factors leading to thyroid destruction or inhibition of thyroid regeneration are important in the pathogenesis of myxoedematous cretinism. Thyroid Laboratory, Division of Endocrinology, Hospital das Clinicas, Faculty of Medicine, University of São Paulo, São Paulo, Brazil
Serum
GERALDO MEDEIROS-NETO KUMIKO TSUBOI NICOLAU LIMA
25-hydroxyvitamin D and colon cancer
SIR,-Dr Garland and colleagues’ study (Nov 18, p 1176) showing that high concentrations of serum 25-hydroxyvitamin D (25-OHD) are associated with reduced colon cancer risk is of considerable importance. As Garland et al point out, colon cancer mortality is highest in areas of the world with little sunshine. Agricultural methods in these temperate areas produce an abundance of meat and fat (associated with high colon-cancer risk) for the western diet whereas cereal and vegetarian-based diets (associated with low colon-cancer risk) prevail in lower latitudes, where there is much sunshine. The correlation of high sunshine exposure with dietary practices associated with low colon-cancer rates now suggests that the protection conferred by such diets may be at least partly attributable to the confounding variable of high sunshine exposure. Even in northern latitudes vegetarianism is frequently associated with "healthy" life-styles that include the consumption of vitamins and high outdoor exposure. The colon-cancer experience in the British Asians is therefore instructive. The frequency of this cancer in this population is low and much the same as that in the Indian subcontinent.2 An Asian population of about 15 000 has been established in Glasgow (latitude 55°52’ north) and the west of Scotland for over thirty years. Between 1961 and 1981 the west of Scotland cancer registry recorded only 2 cases of colon cancer in Asian patients aged 45-64 years against 14-2 cases expected (p < 0’05) on the basis of indigenous population rates.3 The British Asian population also constitutes the largest reservoir of endemic vitamin D deficiency in
