411
has therefore developed from a desire for worthwhile palliation of symptoms with few detrimental effects on quality of life. An advantage of endobronchial therapy is that it can be successful when external beam radiotherapy and surgery are not possible. Systematic study of the value of endobronchial laser in a large series of patients with tracheobronchial tumours showed objective and subjective improvement in just over half when the indications for referral were partial obstruction, complete collapse of lung or lobe, or haemoptysis.2 The facility for repeated treatments, under local or general anaesthesia, when improvement in symptoms had been produced was mentioned as another advantage of this approach. Lately, a study of 28 consecutive patients has helped to identify more precisely those who might benefit from this form of palliation.3 Regional ventilation and perfusion measurements with standard krypton-81m (ventilation) and technetium-99m-labelled macroaggregate (perfusion) scans, together with spirometry, breathlessness scores, and simple wellbeing and performance assessments were done before and shortly after laser therapy. Regional ventilation and perfusion increased after therapy in nearly all patients with main bronchial lesions; ventilation improved more than perfusion, possibly because of direct compression of blood vessels by tumour or mediastinal nodes. Improvements in breathlessness (visual analogue score), wellbeing (visual analogue score and Kamofsky performance index), and six-minute walking distance were also seen in patients with main bronchial tumours, irrespective of whether they had been treated with radiotherapy. Patients who had received previous radiotherapy did less well, perhaps because they had more advanced tumours or were included later in this open study. That 7 patients with intermediate or lobar bronchial obstruction showed no overall improvements in symptoms suggests that such patients are unlikely to benefit. In those who showed a good early response to treatment on these assessments, it would have been interesting to know for how long the improvement in regional ventilation was maintained and in how many further treatment was undertaken. Other attempts to define patients for whom this treatment is especially beneficial suggest that a subset with advanced squamous cell carcinoma and airflow obstruction may benefit more than those with other histological types.4 There may be greater a therapeutic role for local therapy in certain malignant tracheobronchial tumours; reports of low-dose-rate endobronchial radiotherapy in combination with laser therapy have shown that this approach is technically possible; these studies have used either iridium192 or caesium-137 in a flexible polythene catheter or delivery tube, placed adjacent to the tumour under direct vision with a fibreoptic bronchoscope. Future development of endobronchial laser and radiotherapy with tumour sensitising agents may lead to better palliation, increased local response, and even occasional complete remission. Endobronchial stents may also help to preserve large airway patency after treatment and promise to be especially useful when there is extrinsic compression.9 Nevertheless, the high mortality of lung cancer is due to the late presentation, local invasion, and presence of disseminated disease at other sites-factors that do not augur well for endobronchial therapy as a curative procedure. Survival data showing less than 15% of patients alive 1 year after initial treatment suggest that endobronchial laser therapy will continue to be used mainly as a palliative
procedure in selected cases.2 2 deaths occurred in 288 treatment sessions, both as a result of asphyxia from minor haemorrhage in patients with critical narrowing of the trachea or single remaining bronchus; the morbidity and mortality of laser therapy would probably be much higher in the hands of less experienced operators. The overwhelming majority of lung cancers are directly caused by smoking.1O This association was first noted 30 years ago, so it is a remarkable testimony to the continuing influence of the tobacco industry that there is still a need for new treatments. Since young people, especially women, are often targeted by cigarette manufacturers, better palliative treatments for this preventable fatal illness will be needed well into the next century. 1. World Conference on Lung Health. Lung cancer: therapeutic modalities. Am Rev Respir Dis 1990; 141: A400-06. 2. Hetzel MR, Nixon C, Edmonstone WM, et al. Laser therapy in 100 tracheobronchial tumours. Thorax 1985; 40: 341-45. 3. George PJM, Clarke G, Tolfree S, Garrett CPO, Hetzel MR. Changes in
ventilation and perfusion of the lung after endoscopic laser treatment. Thorax 1990; 45: 248-53. 4. Ross DJ, Mohsenifar Z, Koerner SK. Survival characteristics after neodymium-YAG laser photoresection in advanced stage lung cancer. Am Rev Respir Dis 1990; 141: A401. 5. Sudtedja G, Baris G, Van Zandwijk N. Endobronchial brachytherapy in lung cancer. Am Rev Respir Dis 1990; 141: A401. 6. Macha HN, Koch K, Stadler M, Schumacher W, Krumhaar D. New technique for treating occlusive and stenosing tumours of the trachea and main bronchi: endobronchial irradiation by high dose iridium-192 combined with laser canalisation. Thorax 1987; 42: 511-15. 7. O’Driscoll BCR, Burt PA, Notley HM, Stout R, Barber PV. Palliative treatment of lung cancer by high dose rate intraluminal radiotherapy. Am Rev Respir Dis 1990; 141: A404. 8. George PJM, Mantell BS, Rudd RM. Low dose rate endobronchial radiotherapy using caesium-137. Thorax 1990; 45: 310P. 9. George PJM, Irving JD, Mantell BS, Rudd RM. Covered expandable metal stent for recurrent tracheal obstruction. Lancet 1990; 335: 582-84. 10. Doll R, Peto R. Cigarette smoking and bronchial carcinomas: dose and time relationships among regular smokers and lifelong nonsmokers. J Epidemiol Commun Health 1978; 32: 303-13.
ENDOSCOPIC TRANSANAL RESECTION There
are
many local treatments for rectal carcinoma, electrocoagulation, laser, cryosurgery, and irradiation.1-4 A new addition, lately described
including endocavity by Kettlewell and his associates in Oxford,5 is the endoanal use of the genitourinary resectoscope-TAR (transanal resection) rather than TUR (transurethral resection). Kettlewell et al argue an a priori case for transferring techniques that are well established in bladder tumours to both benign and malignant tumours of the rectum. TAR, they assert, is "the method of choice for palliating patients with primary, or recurrent rectal carcinoma and for villous adenoma". These claims require critical evaluation. Villous adenoma and the occasional small mobile carcinoma are satisfactorily excised under direct vision in one piece if the submucosal plane is lifted up by dilute adrenalin. Few proctologists will embrace with much enthusiasm the alternative of multiple sessions with the resectoscope. "Relief of symptoms" is claimed in most of the 23 patients, but the main reason for the surgery is cancer prevention and no follow-up data are provided. Moreover, there are good reasons for providing the histopathologist with the entire lesion in one piece so that the suspicious indurated areas may be sectioned and assessed-sampling errors on random multiple strips must be a real possibility. Discussion of the role of local treatments in advanced cancer or poor risk patients necessarily encompasses the
412
whole range of clinical responses to the suffering and unhappiness caused by the disease. TAR is said to improve bleeding and diarrhoea in about 75% of patients but pain, which is much more important, is ameliorated in only 50%. How do the results of the more orthodox procedurepalliative (but attempted total) excision of the primary tumour plus its relevant mesentery (the mesorectum) by anterior or abdominoperineal excision—compare? Nobody knows, but at least 75% of such patients will probably be saved the misery of death by malignant penetration of the pelvic side walls. However, conventional surgeons who recoil from the concept of TAR cutting deep through the rectal wall into the formidably vascular mesorectum will perhaps be reassured by the mortality figures in the Oxford patients-a modest operative mortality of 11 % for each TAR in patients with an average age of 76 years. Unlike the bladder, the rectum is surrounded by its own mesorectum, which almost invariably contains tumour in advanced cases. Thus total excision and/or irradiation of this block of tissue seems likely to remain the cornerstone of both curative and palliative treatment for the foreseeable future. 1. Crile G, Turnbull RB. The role of electrocoagulation in the treatment of carcinoma of the rectum. Surg Gynecol Obstet 1972; 135: 391-96. 2. Eisenberg HW. Sequential electrocoagulation and resection for carcinoma of the rectum. Surg Gynecol Obstet 1984; 159: 471-74. 3. Bown SG, Barr H, Matthewson K, et al. Endoscopic treatment of inoperable colorectal cancers with Nd: YAG laser. Br J Surg 1986; 73: 949-52. 4. Osborne DR, Higgins AF, Hobbs KEF. Cryosurgery in the management of rectal tumours. Br J Surg 1978; 65: 859-61. 5. Berry AR, Souter RG, Campbell WB, Mortensen NJM, Kettlewell MGW. Endoscopic transanal resection of rectal tumours-a preliminary report of its use. Br J Surg 1990; 77: 134-37.
PRECOCIOUS FAMILIAL GOUT
longer a predominantly male alcoholic preserve: recognition during the past decade that "ancient women" on diuretic treatment are especially prone to gout14 has broadened rheumatologists’ perceptions of the condition. Gout in premenopausal women and in adolescent males remains extraordinarily rare,3-{; but these groups too have now come under scrutiny by Calabrese et al at Guy’s Hospital who conducted a detailed study of 21 "young" men and women referred to their unit because of the precocious development of gout and hyperuricaemia.7 The presenting picture of these patients was not uniform. Although mean age at the time of study was 28 years and gout had developed in the youngest at the age of 12, not all could be deemed young5-the oldest was 49. 70% had a family history of gout and two-thirds had reduced renal function for various reasons. All the women (and nearly 40% of the men) had subnormal renal uric acid clearance relative to creatinine (FEur). The youngest patients had low FE, values. That young Maori (both normouricaemic and hyperuricaemic) also have very low FEur values suggested to Gibson et alB that a genetic renal tubular defect in urate handling might underlie the precocious gout in their cases. Nevertheless, the mean FEur in their patients is not much lower than that identified by the same group for middleaged male gouty patients.9 Juvenile gout occurring against a background of familial, often subclinical, renal impairment has been described previously by this and other groups; 10-12 Macdermot et ap3 called this syndrome familial hyperuricaemic nephropathy. Gout is no
Calabrese et al’ used a method of identifying a renal urate defect to broaden this diagnostic grouping. However, clinically their patients (referred from centres throughout the UK over 5 years) are remarkably heterogeneous. Some are difficult to distinguish from "normal" male gouty subjects (apart from the low FE,), whereas in others the presence of physical abnormalities such as short stature, dysmorphic facies, and short fingers, in addition to renal impairment, suggests that a congenital skeletal-renal syndrome underlies their precocious gout. The Guy’s workers believe that development of gout in their patients before the onset of objective renal impairment, the generally low FEur despite renal impairment (the reverse should apply14), and the rarity of gout in chronic renal failure12 all point to a specific renal tubular defect. Nevertheless, at least some of their patients might simply have had progressive renal failure with various degrees of urate under-excretion,lo,12,14 especially since the degrees of hyperuricaemia showed no predictable relation to the reduction in renal function. Calbrese et al reached the surprising conclusion that young men and women with gout (or hyperuricaemia disproportionate to renal dysfunction), together with their families, should always undergo evaluation of urate handling with a view to starting treatment that would ameliorate renal damage. Where does one draw the line and between disproportionate appropriate hyperuricaemia,15 and what benefit is offered by the painstaking investigations described, compared with straightforward treatment with allopurinol? Are all patients with a low FEur likely to need allopurinol?" Young female patients (and their relatives) with gout or hyperuricaemia may represent a specific subtype, and further case-control studies in urate handling are needed in such cases; many of the male patients in this study are almost indistinguishable from those at the younger end of the regular male gouty age
handling
group. Changing pattern of hospital gout. Ann Rheum Dis 1983; 42: 219 (abstr). 2. Haleem MA. Gout in women. Br J Clin Pract 1984; Nov-Dec: 388-91. 3. Meyers OL, Monteagudo FSE. Gout in females: an analysis of 92 patients. Clin Exp Rheumatol 1985; 3: 105-09. 4. Lally EV, Ho G, Kaplan SR. The clinical spectrum of gouty arthritis in women. Arch Intern Med 1986; 146: 2221-25. 5. Grahame R, Scott JT. Clinical survey of 354 patients with gout. Ann Rheum Dis 1970; 29: 461-68. 6. Currie WJC. Prevalence and incidence of the diagnosis of gout in Great Britain. Ann Rheum Dis 1979; 38: 101-06. 7. Calabrese G, Simmonds HA, Cameron JS, Davies PM. Precocious familial gout with reduced fractional urate clearance and normal purine enzymes. Q J Med 1990; 75: 441-50. 8. Gibson T, Waterworth R, Hatfield P, Robinson G, Bremner K. Hyperuricaemia in young New Zealand Maori men. Adv Exp Med Biol 1984; 165A: 123-28. 9. Gibson T, Highton J, Simmonds HA, Potter CF. Hypertension, renal function and gout. Postgrad Med J 1979; 55 (suppl 3): 21-25. 10. Hollingworth P, Scott JT. Familial gout, hyperuricaemia and renal impairment. Ann Rheum Dis 1983; 42 (suppl 1): 87-88. 11. Simmonds HA, Warren DJ, Cameron JS, Potter CF, Farebrother DA. Familial gout and renal failure in young women. Clin Nephrol 1980; 14: 176-82. 12. Massari PU, Hsu CH, Barnes RV, Fox IH, Gikas PW, Weller JM. Familial hyperuricemia and renal disease. Arch Intern Med 1980; 140: 680-84. 13. Macdermot K, Allsop J, Watts RWE. The date of purine synthesis de novo in blood mononuclear cells in vitro from patients with familial hyperuricaemic nephropathy. Clin Sci 1984; 67: 249-58. 14. Danovitch GM, Weinberger J, Berlyne GM. Uric add in advanced renal failure. Clin Sci 1972; 43: 331-41. 15. Cameron JS, Simmonds HA. Uric acid, gout and the kidney. J Clin Pathol 1981; 34: 1245-54. 1. Macfarlane D, Dieppe P.
has therefore developed from a desire for worthwhile palliation of symptoms with few detrimental effects on quality of life. An advantage of endobronchial therapy is that it can be successful when external beam radiotherapy and surgery are not possible. Systematic study of the value of endobronchial laser in a large series of patients with tracheobronchial tumours showed objective and subjective improvement in just over half when the indications for referral were partial obstruction, complete collapse of lung or lobe, or haemoptysis.2 The facility for repeated treatments, under local or general anaesthesia, when improvement in symptoms had been produced was mentioned as another advantage of this approach. Lately, a study of 28 consecutive patients has helped to identify more precisely those who might benefit from this form of palliation.3 Regional ventilation and perfusion measurements with standard krypton-81m (ventilation) and technetium-99m-labelled macroaggregate (perfusion) scans, together with spirometry, breathlessness scores, and simple wellbeing and performance assessments were done before and shortly after laser therapy. Regional ventilation and perfusion increased after therapy in nearly all patients with main bronchial lesions; ventilation improved more than perfusion, possibly because of direct compression of blood vessels by tumour or mediastinal nodes. Improvements in breathlessness (visual analogue score), wellbeing (visual analogue score and Kamofsky performance index), and six-minute walking distance were also seen in patients with main bronchial tumours, irrespective of whether they had been treated with radiotherapy. Patients who had received previous radiotherapy did less well, perhaps because they had more advanced tumours or were included later in this open study. That 7 patients with intermediate or lobar bronchial obstruction showed no overall improvements in symptoms suggests that such patients are unlikely to benefit. In those who showed a good early response to treatment on these assessments, it would have been interesting to know for how long the improvement in regional ventilation was maintained and in how many further treatment was undertaken. Other attempts to define patients for whom this treatment is especially beneficial suggest that a subset with advanced squamous cell carcinoma and airflow obstruction may benefit more than those with other histological types.4 There may be greater a therapeutic role for local therapy in certain malignant tracheobronchial tumours; reports of low-dose-rate endobronchial radiotherapy in combination with laser therapy have shown that this approach is technically possible; these studies have used either iridium192 or caesium-137 in a flexible polythene catheter or delivery tube, placed adjacent to the tumour under direct vision with a fibreoptic bronchoscope. Future development of endobronchial laser and radiotherapy with tumour sensitising agents may lead to better palliation, increased local response, and even occasional complete remission. Endobronchial stents may also help to preserve large airway patency after treatment and promise to be especially useful when there is extrinsic compression.9 Nevertheless, the high mortality of lung cancer is due to the late presentation, local invasion, and presence of disseminated disease at other sites-factors that do not augur well for endobronchial therapy as a curative procedure. Survival data showing less than 15% of patients alive 1 year after initial treatment suggest that endobronchial laser therapy will continue to be used mainly as a palliative
procedure in selected cases.2 2 deaths occurred in 288 treatment sessions, both as a result of asphyxia from minor haemorrhage in patients with critical narrowing of the trachea or single remaining bronchus; the morbidity and mortality of laser therapy would probably be much higher in the hands of less experienced operators. The overwhelming majority of lung cancers are directly caused by smoking.1O This association was first noted 30 years ago, so it is a remarkable testimony to the continuing influence of the tobacco industry that there is still a need for new treatments. Since young people, especially women, are often targeted by cigarette manufacturers, better palliative treatments for this preventable fatal illness will be needed well into the next century. 1. World Conference on Lung Health. Lung cancer: therapeutic modalities. Am Rev Respir Dis 1990; 141: A400-06. 2. Hetzel MR, Nixon C, Edmonstone WM, et al. Laser therapy in 100 tracheobronchial tumours. Thorax 1985; 40: 341-45. 3. George PJM, Clarke G, Tolfree S, Garrett CPO, Hetzel MR. Changes in
ventilation and perfusion of the lung after endoscopic laser treatment. Thorax 1990; 45: 248-53. 4. Ross DJ, Mohsenifar Z, Koerner SK. Survival characteristics after neodymium-YAG laser photoresection in advanced stage lung cancer. Am Rev Respir Dis 1990; 141: A401. 5. Sudtedja G, Baris G, Van Zandwijk N. Endobronchial brachytherapy in lung cancer. Am Rev Respir Dis 1990; 141: A401. 6. Macha HN, Koch K, Stadler M, Schumacher W, Krumhaar D. New technique for treating occlusive and stenosing tumours of the trachea and main bronchi: endobronchial irradiation by high dose iridium-192 combined with laser canalisation. Thorax 1987; 42: 511-15. 7. O’Driscoll BCR, Burt PA, Notley HM, Stout R, Barber PV. Palliative treatment of lung cancer by high dose rate intraluminal radiotherapy. Am Rev Respir Dis 1990; 141: A404. 8. George PJM, Mantell BS, Rudd RM. Low dose rate endobronchial radiotherapy using caesium-137. Thorax 1990; 45: 310P. 9. George PJM, Irving JD, Mantell BS, Rudd RM. Covered expandable metal stent for recurrent tracheal obstruction. Lancet 1990; 335: 582-84. 10. Doll R, Peto R. Cigarette smoking and bronchial carcinomas: dose and time relationships among regular smokers and lifelong nonsmokers. J Epidemiol Commun Health 1978; 32: 303-13.
ENDOSCOPIC TRANSANAL RESECTION There
are
many local treatments for rectal carcinoma, electrocoagulation, laser, cryosurgery, and irradiation.1-4 A new addition, lately described
including endocavity by Kettlewell and his associates in Oxford,5 is the endoanal use of the genitourinary resectoscope-TAR (transanal resection) rather than TUR (transurethral resection). Kettlewell et al argue an a priori case for transferring techniques that are well established in bladder tumours to both benign and malignant tumours of the rectum. TAR, they assert, is "the method of choice for palliating patients with primary, or recurrent rectal carcinoma and for villous adenoma". These claims require critical evaluation. Villous adenoma and the occasional small mobile carcinoma are satisfactorily excised under direct vision in one piece if the submucosal plane is lifted up by dilute adrenalin. Few proctologists will embrace with much enthusiasm the alternative of multiple sessions with the resectoscope. "Relief of symptoms" is claimed in most of the 23 patients, but the main reason for the surgery is cancer prevention and no follow-up data are provided. Moreover, there are good reasons for providing the histopathologist with the entire lesion in one piece so that the suspicious indurated areas may be sectioned and assessed-sampling errors on random multiple strips must be a real possibility. Discussion of the role of local treatments in advanced cancer or poor risk patients necessarily encompasses the
412
whole range of clinical responses to the suffering and unhappiness caused by the disease. TAR is said to improve bleeding and diarrhoea in about 75% of patients but pain, which is much more important, is ameliorated in only 50%. How do the results of the more orthodox procedurepalliative (but attempted total) excision of the primary tumour plus its relevant mesentery (the mesorectum) by anterior or abdominoperineal excision—compare? Nobody knows, but at least 75% of such patients will probably be saved the misery of death by malignant penetration of the pelvic side walls. However, conventional surgeons who recoil from the concept of TAR cutting deep through the rectal wall into the formidably vascular mesorectum will perhaps be reassured by the mortality figures in the Oxford patients-a modest operative mortality of 11 % for each TAR in patients with an average age of 76 years. Unlike the bladder, the rectum is surrounded by its own mesorectum, which almost invariably contains tumour in advanced cases. Thus total excision and/or irradiation of this block of tissue seems likely to remain the cornerstone of both curative and palliative treatment for the foreseeable future. 1. Crile G, Turnbull RB. The role of electrocoagulation in the treatment of carcinoma of the rectum. Surg Gynecol Obstet 1972; 135: 391-96. 2. Eisenberg HW. Sequential electrocoagulation and resection for carcinoma of the rectum. Surg Gynecol Obstet 1984; 159: 471-74. 3. Bown SG, Barr H, Matthewson K, et al. Endoscopic treatment of inoperable colorectal cancers with Nd: YAG laser. Br J Surg 1986; 73: 949-52. 4. Osborne DR, Higgins AF, Hobbs KEF. Cryosurgery in the management of rectal tumours. Br J Surg 1978; 65: 859-61. 5. Berry AR, Souter RG, Campbell WB, Mortensen NJM, Kettlewell MGW. Endoscopic transanal resection of rectal tumours-a preliminary report of its use. Br J Surg 1990; 77: 134-37.
PRECOCIOUS FAMILIAL GOUT
longer a predominantly male alcoholic preserve: recognition during the past decade that "ancient women" on diuretic treatment are especially prone to gout14 has broadened rheumatologists’ perceptions of the condition. Gout in premenopausal women and in adolescent males remains extraordinarily rare,3-{; but these groups too have now come under scrutiny by Calabrese et al at Guy’s Hospital who conducted a detailed study of 21 "young" men and women referred to their unit because of the precocious development of gout and hyperuricaemia.7 The presenting picture of these patients was not uniform. Although mean age at the time of study was 28 years and gout had developed in the youngest at the age of 12, not all could be deemed young5-the oldest was 49. 70% had a family history of gout and two-thirds had reduced renal function for various reasons. All the women (and nearly 40% of the men) had subnormal renal uric acid clearance relative to creatinine (FEur). The youngest patients had low FE, values. That young Maori (both normouricaemic and hyperuricaemic) also have very low FEur values suggested to Gibson et alB that a genetic renal tubular defect in urate handling might underlie the precocious gout in their cases. Nevertheless, the mean FEur in their patients is not much lower than that identified by the same group for middleaged male gouty patients.9 Juvenile gout occurring against a background of familial, often subclinical, renal impairment has been described previously by this and other groups; 10-12 Macdermot et ap3 called this syndrome familial hyperuricaemic nephropathy. Gout is no
Calabrese et al’ used a method of identifying a renal urate defect to broaden this diagnostic grouping. However, clinically their patients (referred from centres throughout the UK over 5 years) are remarkably heterogeneous. Some are difficult to distinguish from "normal" male gouty subjects (apart from the low FE,), whereas in others the presence of physical abnormalities such as short stature, dysmorphic facies, and short fingers, in addition to renal impairment, suggests that a congenital skeletal-renal syndrome underlies their precocious gout. The Guy’s workers believe that development of gout in their patients before the onset of objective renal impairment, the generally low FEur despite renal impairment (the reverse should apply14), and the rarity of gout in chronic renal failure12 all point to a specific renal tubular defect. Nevertheless, at least some of their patients might simply have had progressive renal failure with various degrees of urate under-excretion,lo,12,14 especially since the degrees of hyperuricaemia showed no predictable relation to the reduction in renal function. Calbrese et al reached the surprising conclusion that young men and women with gout (or hyperuricaemia disproportionate to renal dysfunction), together with their families, should always undergo evaluation of urate handling with a view to starting treatment that would ameliorate renal damage. Where does one draw the line and between disproportionate appropriate hyperuricaemia,15 and what benefit is offered by the painstaking investigations described, compared with straightforward treatment with allopurinol? Are all patients with a low FEur likely to need allopurinol?" Young female patients (and their relatives) with gout or hyperuricaemia may represent a specific subtype, and further case-control studies in urate handling are needed in such cases; many of the male patients in this study are almost indistinguishable from those at the younger end of the regular male gouty age
handling
group. Changing pattern of hospital gout. Ann Rheum Dis 1983; 42: 219 (abstr). 2. Haleem MA. Gout in women. Br J Clin Pract 1984; Nov-Dec: 388-91. 3. Meyers OL, Monteagudo FSE. Gout in females: an analysis of 92 patients. Clin Exp Rheumatol 1985; 3: 105-09. 4. Lally EV, Ho G, Kaplan SR. The clinical spectrum of gouty arthritis in women. Arch Intern Med 1986; 146: 2221-25. 5. Grahame R, Scott JT. Clinical survey of 354 patients with gout. Ann Rheum Dis 1970; 29: 461-68. 6. Currie WJC. Prevalence and incidence of the diagnosis of gout in Great Britain. Ann Rheum Dis 1979; 38: 101-06. 7. Calabrese G, Simmonds HA, Cameron JS, Davies PM. Precocious familial gout with reduced fractional urate clearance and normal purine enzymes. Q J Med 1990; 75: 441-50. 8. Gibson T, Waterworth R, Hatfield P, Robinson G, Bremner K. Hyperuricaemia in young New Zealand Maori men. Adv Exp Med Biol 1984; 165A: 123-28. 9. Gibson T, Highton J, Simmonds HA, Potter CF. Hypertension, renal function and gout. Postgrad Med J 1979; 55 (suppl 3): 21-25. 10. Hollingworth P, Scott JT. Familial gout, hyperuricaemia and renal impairment. Ann Rheum Dis 1983; 42 (suppl 1): 87-88. 11. Simmonds HA, Warren DJ, Cameron JS, Potter CF, Farebrother DA. Familial gout and renal failure in young women. Clin Nephrol 1980; 14: 176-82. 12. Massari PU, Hsu CH, Barnes RV, Fox IH, Gikas PW, Weller JM. Familial hyperuricemia and renal disease. Arch Intern Med 1980; 140: 680-84. 13. Macdermot K, Allsop J, Watts RWE. The date of purine synthesis de novo in blood mononuclear cells in vitro from patients with familial hyperuricaemic nephropathy. Clin Sci 1984; 67: 249-58. 14. Danovitch GM, Weinberger J, Berlyne GM. Uric add in advanced renal failure. Clin Sci 1972; 43: 331-41. 15. Cameron JS, Simmonds HA. Uric acid, gout and the kidney. J Clin Pathol 1981; 34: 1245-54. 1. Macfarlane D, Dieppe P.
