909
EDITORIALS
All aboard for octreotide The accidental discovery of an inhibitor of growth hormone release in sheep hypothalarnusi during an investigation of growth hormone releasing factors in that region led to the isolation of somatostatin, a tetradecapeptide that inhibits secretion of many other hormones and neurotransmitters. Somatostatin is widely distributed throughout the body,often in high concentration in systems and cells that are not necessarily concerned with growth hormone secretion-eg, throughout the nervous system, not only in the region of the hypothalamus, and in the gastrointestinal tract, where it inhibits the secretion of gastrin/pepsin and hydrochloric acid, bile, and vasointestinal peptide.2Somatostatin also inhibits both endocrine and exocrine pancreatic function. One would therefore expect the hormone to have therapeutic application in conditions associated with excess secretion from the hypothalamus/pituitary or gut. However, clinical use of somatostatin is limited because its actions tend to be non-specific and the short half-life (2-3 min) necessitates intravenous administration. Another disadvantage is rebound hormonal hypersecretion after the infusion ceases. These difficulties have largely been overcome by the somatostatin analogue octreotide(’Sandostatin’, SMS 201-995). Octreotide has similar pharmacological effects to the parent compound but a much longer half-life (113 min after subcutaneous administration), so subcutaneous therapy is possible. Octreotide is also far more selective with respect to inhibition of growth hormone and there is no rebound hypersecretion. Secretion of pancreatic polypeptide, gastrin, secretin, and motilin is inhibited,45 but there is only slight suppression of other pituitary hormones such as thyrotropin and no effect on corticotropin
production and posterior pituitary activity.6 In acromegaly, octreotide lowers secretion of growth hormone and also that of insulin-like growth factor 1 IGF-1), together with a reduction in tumour size and clinical manifestations of the disease.7 The main
morbidity
and
mortality
in
acromegaly
cause of is cardiovascular
disease-hypertension and/or cardiomyopathy. Octreotide reversed cardiac failure after only a few weeks’ treatment and the cardiothoracic ratio returned to normal in three patients with severe cardiac failure associated with acromegaly.8 Withdrawal of the drug led to a deterioration of cardiac function, with a rise in growth hormone concentrations. Octreotide inhibits activity of other tumours with somatostatin receptors-eg, thyrotropin tumours9 and infiltrative corticotropin-secreting pituitary tumours and non-secreting pituitary adenomas.11 Symptoms of carcinoid syndrome and vipoma can be controlled by the analogue, which is also helpful in the treatment of glucagonoma and possibly malignant insulinoma.12 Localisation of somatostatin-binding receptors in vivo in human tumours13 raises the possibility of their subsequent target irradiation with isotopes attached to a somatostatin analogue; this approach might be especially beneficial in patients with metastases. Somatostatin receptor content of the tumour tissue shows a positive correlation with hormonal secretion and responsiveness to octreotide.14 Controlled clinical trials are therefore needed to assess the antimitotic activity of the analogue in different tumours. In rodents octreotide inhibits the growth of transplantable tumours such as chondrosarcomas in rats and human breast cancer cell lines in mice, but the clinical implication of these findings is unknown. How do somatostatin and octreotide suppress cancerous cell growth? Direct inhibition of the tumour via specific somatostatin receptors is the favoured mechanism for pituitary tumours that cause acromegaly or for gastrointestinal tumours that respond to octreotide.15 Inhibitory effects on growth hormone (which may act as a growth factor in some tumours), insulin, gut hormones, or IGF-1 are other possibilities. Octreotide also enhances natural killer cell function in carcinoid tumours and islet-cell carcinomas." Since somatostatin delays carbohydrate absorption and inhibits secretion of the counter-regulatory hormones growth hormone and glucagon much more than that of insulin, one would expect a favourable effect on carbohydrate tolerance in diabetes." Although octreotide did not prevent early-morning hyperglycaemia, late-night ketogenesis was reduced, as indicated by lower plasma levels of 3-hydroxvbutyrate compared with placebo and significantly reduced ketogenesis after insulin deprivation.18 Octreotide may therefore be useful in the prophylactic
910
treatment of diabetic ketoacidosis.
patients
who
are at
risk of
frequent
Because of its insulin-sparing effect, octreotide might also be a useful adjunct for treating both type I and insulindependent type II diabetes, to reduce hyperinsulinaemia and hence the progression of atherosclerosis. Reduction in the concentrations of growth hormone or of IGF-1 might help to prevent the development of microangiopathy or retard the development of established microangiopathic lesions. That octreotide reduces glomerular hyperfiltration in insulin-dependent diabetic patients with nephromegaly, 19 independently of their blood sugar control, supports the view that the analogue might delay or even prevent progression to late diabetic nephropathy. Reduction in both splanchnic bloodflow and portal venous pressure in cirrhosis was one of the earliest observed effects of the drugs Octreotide may be a useful adjunct to injection sclerosing therapy in the initial control of acute variceal bleeding2l and also in long-term management. By contrast, bleeding from peptic ulcers does not seem to be
affected.22 Octreotide accelerates the closure of pancreatic and enterocutaneous fistulae, 2324 presumably via a reduction in pancreatic exocrine secretion 25 The observation that octreotide may reduce stool output in infants with severe refractory secretory diarrhoea26 and also the profuse watery diarrhoea of patients with AID S27 may relate to its ability to stimulate electrolyte and water absorption28 and inhibit epithelial transport and intestinal motility29 as well as the release of gut hormones.4,5 Whilst many of the effects of somatostatin and
might have been anticipated from these agents’ pharmacological properties, some were unexpected. Thus the analogue relieves the headache associated with pituitary adenoma: pain was relieved within minutes of injection and the effect lasted for 6-8 hours, independently of tumour shrinkage. Pain relief has also been reported in patients with generalised cancer.31 The mechanism for the analgesia is not known, but somatostatin and octreotide may inhibit neurotransmission, possibly via an effect on
octreotide
substance P release. Another unexpected effect of both somatostatin and octreotide is their action in psoriasis. Thus, 100 g of octreotide daily alleviated psoriasis-without lowering growth hormone concentrations or those of IGF-1.32 The mechanism of action in psoriasis is unknown. In this issue (p 900) Dr Prelevic and her colleagues report the effect of octreotide on ovarian activity in women with polycystic ovaries. The polycystic ovary syndrome is the commonest cause of menstrual dysfunction and infertility in hospital practice and is difficult to treat. Whilst antiandrogen therapy combined with oestradiol may restore menstrual cyclicity and relieve hirsuties and acne, there are side-effects, especially in patients who are obese, and these drugs cannot be used in women who wish to conceive. Dexamethasone has been disappointing in the treatment of hirsuties and is also inappropriate for infertile women. Administration of gonadotropin releasing hormone agonists to lower the raised
hormone (LH) concentrations is not beneficial. Thus it is encouraging that daily administration of octreotide for only a week can lower hyperinsulinaemia and diminish the raised LH and circulating androgen. concentrations in women with polycystic ovaries. Whether octreotide can also influence ovulation in women with polycystic ovaries or with other types of anovulatory infertility is not known. Clinical use and acceptability of octreotide have been limited by the fact that the drug has to be given by (subcutaneous) injection twice a day, or at the very least once. Availability of a more acceptable mode of administration, such as an intranasal spray, would extend the potential therapeutic applications.
luteinising
1. Brazeau P, Vale W, Burgus R, et al. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 1973; 179: 77-79. 2. Reichlin S. Somatostatin. Parts 1 and 2. N Engl J Med 1983; 309: 1495-501; 1556-63. 3. Bauer W, Briner U, Doepfner W, et al. SMS 201-995: a very potent and selective octapeptide analogue of somatostatin with prolonged action. Life Sci 1982; 31: 1133-40. 4. Creutzfeldt W, Lembcke B, Folsch UR, et al. Effect of somatostatin analogue (SMS 201-995, Sandostatin) on pancreatic secretion in humans. Am J Med 1987; 82 (suppl 5B): 49-54. 5. Kraenzlin ME, Wood SM, Neufeld M, et al. Effect of long acting somatostatin analogue, SMS 201-995, on gut hormone secretion in normal subjects. Experientia 1985; 41: 738-40. 6. Lightman SL, Fox P, Dunne MJ. The effect of SMS 201-995 a long-acting somatostatin analogue on anterior pituitary function in healthy male volunteers. Scand J Gastroenterol 1986; 21 (suppl 119). 84-95. 7. Harris AG, Prestele H, Herold K, et al. Long-term efficacy of Sandostatin (SMS 201-995, octreotide) in 178 acromegalic patients. Results from the International Multicentre Acromegaly Study group In: Lamberts SWJ, ed. Sandostatin in the treatment of acromegaly. consensus round table, Amsterdam, 1987. Berlin: Springer, 1988; 117-25. 8. Chanson P, Timsit J, Masquet C, et al. Heart failure responding to octreotide in patient with acromegaly. Lancet 1989; i: 1263-64. 9. Gesundheit N, Petrick PA, Nissim M, et al. Thyrotropin-secreting pituitary adenomas: clinical and biochemical heterogeneity. Case report and follow-up of nine patients. Ann Intern Med 1989; 111: 827-34. 10. Lamberts SWJ, Utterlinden P, Klijn JMG. The effect of the long-acting somatostatin analogue SMS 201-995 on ACTH secretion in Nelson’s syndrome and Cushing’s syndrome. Acta Endocrinol 1989; 120: 760-66. 11. Warnet A, Timsit J, Chanson P, et al. The effect of somatostatin analog on chiasmal dysfunction from pituitary macroadenomas. J Neurosurg 1989; 71: 687-90. 12. Gorden P. Somatostatin and somatostatin analog (SMS 201-995) in treatment of hormone-secreting tumors of the pituitary and gastrointestinal tract and non-neoplastic diseases of the gut. Ann Intern Med 1989; 110: 33-50. 13. Krenning EP, Bakker WH, Breeman WAP, et al. Localisation of endocrine-related tumours with radioiodinated analogue of somatostatin. Lancet 1989; i: 242-44. 14. Lamberts SWJ, Hofland LJ, van Koetsveld PM, et al. Parallel in vivo and in vitro detection of functional somatostatin receptors in human endocrine pancreatic tumors: consequences with regard to diagnosis, localization, and therapy. J Clin Endocrinol Metab 1990; 71: 566-74 15. Lamberts SWJ, Krenning EP, Klijn JG, et al. The clinical use of somatostatin analogs in the treatment of cancer. Clin Endocrinol Metab
1990; 4: 29-49. RE, Kvols LK, Strehlo B,
16. Ritts
et al. Immunologic studies of patients with malignant neuroendocrine carcinomas and responses to somatostatin analog (SMS 201-995, Sandostatin). Proc Am Assoc Cancer Res 1989; 30: (abstr 1119). 17. Harris AG, Gutniak M, Efendic S. Somatostatin analogue therapy of diabetes mellitus. In: Bailey CJ, Flatt PR, eds. New antidiabetic drugs. Nishimura: Smith Gordon, 1990: 279-88. 18. Aarsen RSR, Bruining GJ, Grose WFA, et al. Long-acting somatostatin analogue (Sandostatin) reduces late night insulmopenic ketogenesisin diabetic teenagers. Acta Endocrinol 1987; 116 (suppl 286): 45-53
911
19. Serri O, Beauregard H, Brazeau P, et al. Sandostatin reduces increased kidney function and size in type I diabetes. Diabetologia 1990; 33 (suppl): A76. 20. Morgan JS, Groszmann RJ. Somatostatin in portal hypertension. Dig Dis Sci 1989; 34: 40-47S. 21. McKee R. A study of octreotide in oesophageal varices. Digestion 1990; 45 (suppl 1): 60-65. 22. Christiansen J, Ottenjann R, Von Arx F, et al. Placebo-controlled trial with the somatostatin analogue SMS 201-995 in peptic ulcer bleeding. Gastroenterology 1989; 97: 568-74. 23. Prinz RA, Pickleman J, Hoffman JP. Treatment of pancreatic cutaneous fistulas with a somatostatin analog. Am J Surg 1988; 155: 36-42. 24. Nubiola P, Badia JM, Martinez-Rodenas F, et al. Treatment of 27 postoperative enterocutaneous fistulas with the long half-life somatostatin analog SMS 201-995. Ann Surg 1989; 210: 56-58. 25. Williams ST, Woltering EA, O’Donsio TM, et al. Effect of octreotide acetate on pancreatic exocrine function. Am J Surg 1989; 157: 459-62. 26. Jaros W, Biller J, Greer S, et al. Successful treatment of idiopathic secretory diarrhea of infancy with the somatostatin analog SMS 201-995. Gastroenterology 1988; 94: 189-93. 27. Cello JP, Grendell J, Basuk P, et al. Controlled clinical trial of octreotide for refractory AIDS-associated diarrhea. Gastroenterology 1990; 98 (suppl): A163. 28. Vinik AI, Isai ST, Moattari AR, et al. Somatostatin analog (SMS 201-995) in the management of gastroenteropancreatic tumors and diarrhea syndrome. Am J Med 1986; 81 (suppl 6B): 23-40. 29. Edwards CA, Cann PA, Read NW, et al. The effects of somatostatin analogue SMS 201-995 on fluid and electrolyte transport in a patient with secretory diarrhoea. Scand J Gastroenterol 1986; 21 (suppl 119): 259-61. 30. Williams G, Ball JA, Lawson RA, et al. Analgesic effect of somatostatin analogue (octreotide) in headache associated with pituitary tumours. Br Med J 1987; 295: 247-48. 31. Penn RD, Paice JA, Kroin JS, et al. Intrathecal octreotide for cancer pain. Lancet 1990; i: 738. 32. Camisa C, Mehle AL, Benedetto E, et al. A somatostatin analog (octreotide acetate) vs placebo in the treatment of psoriasis. Clin Res 1989; 37: 968A.
Mental health services for migrants in Europe The mental health of immigrants in the UK has lately been the subject of intense scrutiny.l-4 However, the issues have wider importance, as shown by the migration conference held earlier this year under the joint auspices of the International Organisation for Migration and the World Health Organisation. The importance of migrant groups is likely to increase still further after the adoption of the single European market in 1992.5 One of the most consistent findings in UK studies of immigrants is an increased rate of admission for
schizophrenia and related illnesses, but the underlying reasons may not be the same in all migrant groups. For example, the exceptionally high rates of schizophrenia that have been reported among immigrants in some studies6 cannot be explained entirely by factors such as the age structure of the migrant population in question. However, standardisation for age does appear to reduce the disparity in the rates between English-born subjects and other immigrant subgroups.’ Longitudinal studies on patients who were initially diagnosed as psychotic indicate that some migrant groups use inpatient psychiatric services less than the indigenous population.8 Some studies suggest that immigrants may have reduced rates of non-psychotic disorders, but others have found no difference or have
even
shown
an
increased
Rack9 suggests, on the basis of anecdotal evidence, that there may be a considerable unmet need for psychological intervention among immigrants, but attempts to test this hypothesis have not provided a clear answer. For example, community surveys carried out in the UK have not usually found high rates of psychiatric morbidity among migrants. However, the findings are often difficult to interpret because of methodological difficulties or because the comparison groups may not have been appropriate.’ Thus anxiety that many immigrants may not be getting the type of service that they require has persisted,l° and much attention has focused on the relation between such individuals and those who provide care." Special transcultural psychiatry units,12 day centres, 13 or other voluntary facilities that offer a specific service to ethnic minority subgroups14 have been established in some areas to help circumvent cultural barriers between indigenous psychiatrists and their immigrant patients. To what extent does the British experience mirror that of mainland Europe? A 1988 WHO reportl-5 suggests that in 1974 about 5-5 million immigrants from southern European countries were living in the northern and western parts of the continent. Many of these people are migrant workers.16 For example, a survey of Turkish workers in the Netherlandsl’ showed that neurotic illnesses may be common in such subjects, and were often associated with concern for their families at home. The need to recognise heterogeneity among foreign-born groups is illustrated by a German
study,18 which showed little evidence for a single guest-worker syndrome that could be applied across different ethnic groups. Similarly, in a study in Denmark, Jensen et a119 found notable differences in the mode of presentation between refugees and other immigrants. Nevertheless, in both groups treatment was often terminated prematurely, either by the patient or by the therapist, and the Danish workers believe that special transcultural teams would be helpful. Levandero has described the formation of a self-help group for immigrant women in Sweden, and there have been attempts to provide native psychiatric therapists in neighbouring Finland.Z1 Many immigrants turn to unconventional agencies for help-eg, African women living in Paris may direct specific psychological and behavioural problems in children towards traditional healers and holy men.22 In a study of African immigrants attending two voluntary centres in Rome,23 the apparent prevalence of psychiatric symptoms was low, but assessment of subjects was noted to be difficult because the scales used were culturally inappropriate. Van der Stuyft and colleagues24 in Belgium suggest that the effects of acculturation are complex. Immigrants there tended to underutilise primary health care services for milder psychological
EDITORIALS
All aboard for octreotide The accidental discovery of an inhibitor of growth hormone release in sheep hypothalarnusi during an investigation of growth hormone releasing factors in that region led to the isolation of somatostatin, a tetradecapeptide that inhibits secretion of many other hormones and neurotransmitters. Somatostatin is widely distributed throughout the body,often in high concentration in systems and cells that are not necessarily concerned with growth hormone secretion-eg, throughout the nervous system, not only in the region of the hypothalamus, and in the gastrointestinal tract, where it inhibits the secretion of gastrin/pepsin and hydrochloric acid, bile, and vasointestinal peptide.2Somatostatin also inhibits both endocrine and exocrine pancreatic function. One would therefore expect the hormone to have therapeutic application in conditions associated with excess secretion from the hypothalamus/pituitary or gut. However, clinical use of somatostatin is limited because its actions tend to be non-specific and the short half-life (2-3 min) necessitates intravenous administration. Another disadvantage is rebound hormonal hypersecretion after the infusion ceases. These difficulties have largely been overcome by the somatostatin analogue octreotide(’Sandostatin’, SMS 201-995). Octreotide has similar pharmacological effects to the parent compound but a much longer half-life (113 min after subcutaneous administration), so subcutaneous therapy is possible. Octreotide is also far more selective with respect to inhibition of growth hormone and there is no rebound hypersecretion. Secretion of pancreatic polypeptide, gastrin, secretin, and motilin is inhibited,45 but there is only slight suppression of other pituitary hormones such as thyrotropin and no effect on corticotropin
production and posterior pituitary activity.6 In acromegaly, octreotide lowers secretion of growth hormone and also that of insulin-like growth factor 1 IGF-1), together with a reduction in tumour size and clinical manifestations of the disease.7 The main
morbidity
and
mortality
in
acromegaly
cause of is cardiovascular
disease-hypertension and/or cardiomyopathy. Octreotide reversed cardiac failure after only a few weeks’ treatment and the cardiothoracic ratio returned to normal in three patients with severe cardiac failure associated with acromegaly.8 Withdrawal of the drug led to a deterioration of cardiac function, with a rise in growth hormone concentrations. Octreotide inhibits activity of other tumours with somatostatin receptors-eg, thyrotropin tumours9 and infiltrative corticotropin-secreting pituitary tumours and non-secreting pituitary adenomas.11 Symptoms of carcinoid syndrome and vipoma can be controlled by the analogue, which is also helpful in the treatment of glucagonoma and possibly malignant insulinoma.12 Localisation of somatostatin-binding receptors in vivo in human tumours13 raises the possibility of their subsequent target irradiation with isotopes attached to a somatostatin analogue; this approach might be especially beneficial in patients with metastases. Somatostatin receptor content of the tumour tissue shows a positive correlation with hormonal secretion and responsiveness to octreotide.14 Controlled clinical trials are therefore needed to assess the antimitotic activity of the analogue in different tumours. In rodents octreotide inhibits the growth of transplantable tumours such as chondrosarcomas in rats and human breast cancer cell lines in mice, but the clinical implication of these findings is unknown. How do somatostatin and octreotide suppress cancerous cell growth? Direct inhibition of the tumour via specific somatostatin receptors is the favoured mechanism for pituitary tumours that cause acromegaly or for gastrointestinal tumours that respond to octreotide.15 Inhibitory effects on growth hormone (which may act as a growth factor in some tumours), insulin, gut hormones, or IGF-1 are other possibilities. Octreotide also enhances natural killer cell function in carcinoid tumours and islet-cell carcinomas." Since somatostatin delays carbohydrate absorption and inhibits secretion of the counter-regulatory hormones growth hormone and glucagon much more than that of insulin, one would expect a favourable effect on carbohydrate tolerance in diabetes." Although octreotide did not prevent early-morning hyperglycaemia, late-night ketogenesis was reduced, as indicated by lower plasma levels of 3-hydroxvbutyrate compared with placebo and significantly reduced ketogenesis after insulin deprivation.18 Octreotide may therefore be useful in the prophylactic
910
treatment of diabetic ketoacidosis.
patients
who
are at
risk of
frequent
Because of its insulin-sparing effect, octreotide might also be a useful adjunct for treating both type I and insulindependent type II diabetes, to reduce hyperinsulinaemia and hence the progression of atherosclerosis. Reduction in the concentrations of growth hormone or of IGF-1 might help to prevent the development of microangiopathy or retard the development of established microangiopathic lesions. That octreotide reduces glomerular hyperfiltration in insulin-dependent diabetic patients with nephromegaly, 19 independently of their blood sugar control, supports the view that the analogue might delay or even prevent progression to late diabetic nephropathy. Reduction in both splanchnic bloodflow and portal venous pressure in cirrhosis was one of the earliest observed effects of the drugs Octreotide may be a useful adjunct to injection sclerosing therapy in the initial control of acute variceal bleeding2l and also in long-term management. By contrast, bleeding from peptic ulcers does not seem to be
affected.22 Octreotide accelerates the closure of pancreatic and enterocutaneous fistulae, 2324 presumably via a reduction in pancreatic exocrine secretion 25 The observation that octreotide may reduce stool output in infants with severe refractory secretory diarrhoea26 and also the profuse watery diarrhoea of patients with AID S27 may relate to its ability to stimulate electrolyte and water absorption28 and inhibit epithelial transport and intestinal motility29 as well as the release of gut hormones.4,5 Whilst many of the effects of somatostatin and
might have been anticipated from these agents’ pharmacological properties, some were unexpected. Thus the analogue relieves the headache associated with pituitary adenoma: pain was relieved within minutes of injection and the effect lasted for 6-8 hours, independently of tumour shrinkage. Pain relief has also been reported in patients with generalised cancer.31 The mechanism for the analgesia is not known, but somatostatin and octreotide may inhibit neurotransmission, possibly via an effect on
octreotide
substance P release. Another unexpected effect of both somatostatin and octreotide is their action in psoriasis. Thus, 100 g of octreotide daily alleviated psoriasis-without lowering growth hormone concentrations or those of IGF-1.32 The mechanism of action in psoriasis is unknown. In this issue (p 900) Dr Prelevic and her colleagues report the effect of octreotide on ovarian activity in women with polycystic ovaries. The polycystic ovary syndrome is the commonest cause of menstrual dysfunction and infertility in hospital practice and is difficult to treat. Whilst antiandrogen therapy combined with oestradiol may restore menstrual cyclicity and relieve hirsuties and acne, there are side-effects, especially in patients who are obese, and these drugs cannot be used in women who wish to conceive. Dexamethasone has been disappointing in the treatment of hirsuties and is also inappropriate for infertile women. Administration of gonadotropin releasing hormone agonists to lower the raised
hormone (LH) concentrations is not beneficial. Thus it is encouraging that daily administration of octreotide for only a week can lower hyperinsulinaemia and diminish the raised LH and circulating androgen. concentrations in women with polycystic ovaries. Whether octreotide can also influence ovulation in women with polycystic ovaries or with other types of anovulatory infertility is not known. Clinical use and acceptability of octreotide have been limited by the fact that the drug has to be given by (subcutaneous) injection twice a day, or at the very least once. Availability of a more acceptable mode of administration, such as an intranasal spray, would extend the potential therapeutic applications.
luteinising
1. Brazeau P, Vale W, Burgus R, et al. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 1973; 179: 77-79. 2. Reichlin S. Somatostatin. Parts 1 and 2. N Engl J Med 1983; 309: 1495-501; 1556-63. 3. Bauer W, Briner U, Doepfner W, et al. SMS 201-995: a very potent and selective octapeptide analogue of somatostatin with prolonged action. Life Sci 1982; 31: 1133-40. 4. Creutzfeldt W, Lembcke B, Folsch UR, et al. Effect of somatostatin analogue (SMS 201-995, Sandostatin) on pancreatic secretion in humans. Am J Med 1987; 82 (suppl 5B): 49-54. 5. Kraenzlin ME, Wood SM, Neufeld M, et al. Effect of long acting somatostatin analogue, SMS 201-995, on gut hormone secretion in normal subjects. Experientia 1985; 41: 738-40. 6. Lightman SL, Fox P, Dunne MJ. The effect of SMS 201-995 a long-acting somatostatin analogue on anterior pituitary function in healthy male volunteers. Scand J Gastroenterol 1986; 21 (suppl 119). 84-95. 7. Harris AG, Prestele H, Herold K, et al. Long-term efficacy of Sandostatin (SMS 201-995, octreotide) in 178 acromegalic patients. Results from the International Multicentre Acromegaly Study group In: Lamberts SWJ, ed. Sandostatin in the treatment of acromegaly. consensus round table, Amsterdam, 1987. Berlin: Springer, 1988; 117-25. 8. Chanson P, Timsit J, Masquet C, et al. Heart failure responding to octreotide in patient with acromegaly. Lancet 1989; i: 1263-64. 9. Gesundheit N, Petrick PA, Nissim M, et al. Thyrotropin-secreting pituitary adenomas: clinical and biochemical heterogeneity. Case report and follow-up of nine patients. Ann Intern Med 1989; 111: 827-34. 10. Lamberts SWJ, Utterlinden P, Klijn JMG. The effect of the long-acting somatostatin analogue SMS 201-995 on ACTH secretion in Nelson’s syndrome and Cushing’s syndrome. Acta Endocrinol 1989; 120: 760-66. 11. Warnet A, Timsit J, Chanson P, et al. The effect of somatostatin analog on chiasmal dysfunction from pituitary macroadenomas. J Neurosurg 1989; 71: 687-90. 12. Gorden P. Somatostatin and somatostatin analog (SMS 201-995) in treatment of hormone-secreting tumors of the pituitary and gastrointestinal tract and non-neoplastic diseases of the gut. Ann Intern Med 1989; 110: 33-50. 13. Krenning EP, Bakker WH, Breeman WAP, et al. Localisation of endocrine-related tumours with radioiodinated analogue of somatostatin. Lancet 1989; i: 242-44. 14. Lamberts SWJ, Hofland LJ, van Koetsveld PM, et al. Parallel in vivo and in vitro detection of functional somatostatin receptors in human endocrine pancreatic tumors: consequences with regard to diagnosis, localization, and therapy. J Clin Endocrinol Metab 1990; 71: 566-74 15. Lamberts SWJ, Krenning EP, Klijn JG, et al. The clinical use of somatostatin analogs in the treatment of cancer. Clin Endocrinol Metab
1990; 4: 29-49. RE, Kvols LK, Strehlo B,
16. Ritts
et al. Immunologic studies of patients with malignant neuroendocrine carcinomas and responses to somatostatin analog (SMS 201-995, Sandostatin). Proc Am Assoc Cancer Res 1989; 30: (abstr 1119). 17. Harris AG, Gutniak M, Efendic S. Somatostatin analogue therapy of diabetes mellitus. In: Bailey CJ, Flatt PR, eds. New antidiabetic drugs. Nishimura: Smith Gordon, 1990: 279-88. 18. Aarsen RSR, Bruining GJ, Grose WFA, et al. Long-acting somatostatin analogue (Sandostatin) reduces late night insulmopenic ketogenesisin diabetic teenagers. Acta Endocrinol 1987; 116 (suppl 286): 45-53
911
19. Serri O, Beauregard H, Brazeau P, et al. Sandostatin reduces increased kidney function and size in type I diabetes. Diabetologia 1990; 33 (suppl): A76. 20. Morgan JS, Groszmann RJ. Somatostatin in portal hypertension. Dig Dis Sci 1989; 34: 40-47S. 21. McKee R. A study of octreotide in oesophageal varices. Digestion 1990; 45 (suppl 1): 60-65. 22. Christiansen J, Ottenjann R, Von Arx F, et al. Placebo-controlled trial with the somatostatin analogue SMS 201-995 in peptic ulcer bleeding. Gastroenterology 1989; 97: 568-74. 23. Prinz RA, Pickleman J, Hoffman JP. Treatment of pancreatic cutaneous fistulas with a somatostatin analog. Am J Surg 1988; 155: 36-42. 24. Nubiola P, Badia JM, Martinez-Rodenas F, et al. Treatment of 27 postoperative enterocutaneous fistulas with the long half-life somatostatin analog SMS 201-995. Ann Surg 1989; 210: 56-58. 25. Williams ST, Woltering EA, O’Donsio TM, et al. Effect of octreotide acetate on pancreatic exocrine function. Am J Surg 1989; 157: 459-62. 26. Jaros W, Biller J, Greer S, et al. Successful treatment of idiopathic secretory diarrhea of infancy with the somatostatin analog SMS 201-995. Gastroenterology 1988; 94: 189-93. 27. Cello JP, Grendell J, Basuk P, et al. Controlled clinical trial of octreotide for refractory AIDS-associated diarrhea. Gastroenterology 1990; 98 (suppl): A163. 28. Vinik AI, Isai ST, Moattari AR, et al. Somatostatin analog (SMS 201-995) in the management of gastroenteropancreatic tumors and diarrhea syndrome. Am J Med 1986; 81 (suppl 6B): 23-40. 29. Edwards CA, Cann PA, Read NW, et al. The effects of somatostatin analogue SMS 201-995 on fluid and electrolyte transport in a patient with secretory diarrhoea. Scand J Gastroenterol 1986; 21 (suppl 119): 259-61. 30. Williams G, Ball JA, Lawson RA, et al. Analgesic effect of somatostatin analogue (octreotide) in headache associated with pituitary tumours. Br Med J 1987; 295: 247-48. 31. Penn RD, Paice JA, Kroin JS, et al. Intrathecal octreotide for cancer pain. Lancet 1990; i: 738. 32. Camisa C, Mehle AL, Benedetto E, et al. A somatostatin analog (octreotide acetate) vs placebo in the treatment of psoriasis. Clin Res 1989; 37: 968A.
Mental health services for migrants in Europe The mental health of immigrants in the UK has lately been the subject of intense scrutiny.l-4 However, the issues have wider importance, as shown by the migration conference held earlier this year under the joint auspices of the International Organisation for Migration and the World Health Organisation. The importance of migrant groups is likely to increase still further after the adoption of the single European market in 1992.5 One of the most consistent findings in UK studies of immigrants is an increased rate of admission for
schizophrenia and related illnesses, but the underlying reasons may not be the same in all migrant groups. For example, the exceptionally high rates of schizophrenia that have been reported among immigrants in some studies6 cannot be explained entirely by factors such as the age structure of the migrant population in question. However, standardisation for age does appear to reduce the disparity in the rates between English-born subjects and other immigrant subgroups.’ Longitudinal studies on patients who were initially diagnosed as psychotic indicate that some migrant groups use inpatient psychiatric services less than the indigenous population.8 Some studies suggest that immigrants may have reduced rates of non-psychotic disorders, but others have found no difference or have
even
shown
an
increased
Rack9 suggests, on the basis of anecdotal evidence, that there may be a considerable unmet need for psychological intervention among immigrants, but attempts to test this hypothesis have not provided a clear answer. For example, community surveys carried out in the UK have not usually found high rates of psychiatric morbidity among migrants. However, the findings are often difficult to interpret because of methodological difficulties or because the comparison groups may not have been appropriate.’ Thus anxiety that many immigrants may not be getting the type of service that they require has persisted,l° and much attention has focused on the relation between such individuals and those who provide care." Special transcultural psychiatry units,12 day centres, 13 or other voluntary facilities that offer a specific service to ethnic minority subgroups14 have been established in some areas to help circumvent cultural barriers between indigenous psychiatrists and their immigrant patients. To what extent does the British experience mirror that of mainland Europe? A 1988 WHO reportl-5 suggests that in 1974 about 5-5 million immigrants from southern European countries were living in the northern and western parts of the continent. Many of these people are migrant workers.16 For example, a survey of Turkish workers in the Netherlandsl’ showed that neurotic illnesses may be common in such subjects, and were often associated with concern for their families at home. The need to recognise heterogeneity among foreign-born groups is illustrated by a German
study,18 which showed little evidence for a single guest-worker syndrome that could be applied across different ethnic groups. Similarly, in a study in Denmark, Jensen et a119 found notable differences in the mode of presentation between refugees and other immigrants. Nevertheless, in both groups treatment was often terminated prematurely, either by the patient or by the therapist, and the Danish workers believe that special transcultural teams would be helpful. Levandero has described the formation of a self-help group for immigrant women in Sweden, and there have been attempts to provide native psychiatric therapists in neighbouring Finland.Z1 Many immigrants turn to unconventional agencies for help-eg, African women living in Paris may direct specific psychological and behavioural problems in children towards traditional healers and holy men.22 In a study of African immigrants attending two voluntary centres in Rome,23 the apparent prevalence of psychiatric symptoms was low, but assessment of subjects was noted to be difficult because the scales used were culturally inappropriate. Van der Stuyft and colleagues24 in Belgium suggest that the effects of acculturation are complex. Immigrants there tended to underutilise primary health care services for milder psychological
