- Email: [email protected]
Hyperuricaemia
184
vagal and sympathetic responses. Our work has shown that exercise training reduces the sympathetic component of the reflex in normotensive subjects without changing the sensitivity of the reflex. The method of baroreflex assessment Somers et al use suggests that exercise training increases the sensitivity of the vagal component of the reflex in borderline hypertension, but from this work it is not possible to assess the impact of training on the total reflex and on the sympathetic component in particular.
Baker Medical Research Institute, Alfred Hospital, Prahran 3181, Victoria, Australia
BRONWYN A. KINGWELL ANTHONY M. DART GARRY L. JENNINGS PAUL I. KORNER
Jennings GL, Meredith IT, Kingwell BA, Esler MD, Dart AM, Korner PI. The effect of exercise training on cardiac dimensions, sympathetic activity and the arterial baroreflex. Int Soc Hypertens 1990; S35. 2. Pickering TG, Gribbin B, Sleight P. Comparison of reflex heart rate responses to rising and falling arterial pressure in man. Cardiovasc Res 1972; 6: 277-83. 3. Smyth HS, Sleight P, Pickering GW. Reflex regulation of arterial pressure during sleep in man: a quantitative method of assessing baroreflex sensitivity. Circ Res 1.
1969; 24: 109-21. 4. Weinstock M, Komer PI, Head GA, Dorward P. Differentiation of cardiac baroreflex properties by cuff and drug methods in two rabbit strains. Am J Physiol 1988; 255: R654-64.
urine specimen and in a concurrent sample of serum.’ The product of urinary uric acid (mg/dl) and plasma creatinine (mg/dl) divided by the urinary creatinine (mg/dl) provides an assessment of uric acid excretion in mg/dl glomerular filtrate or in ml/min after the glomerular filtration rate (GFR) has been normalised to 100 ml/min. Because the urinary flow rate appears both in the calculation of the excretion rate and in the assessment of GFR by creatinine clearance, its numerical value cancels out and a timed urine collection is unnecessary. The mean in normal young men without dietary restriction is 0-40 mg/dl. I reserve more intensive evaluations for the small subset of hyperuricaemic patients whose screening values exceed 0 60 mg/dl. I agree with Kelley and Palella2 that "the most important single test in the hyperuricemic patient is analysis of the urine for uric acid." In routine practice, however, this evaluation is often neglected. The most likely explanation for this discrepancy is that many clinicians recognise both the poor precision of single, 24 h specimens and the very low yield of the test in patients selected only for hyperuricaemia. Judicious use of a screening test, based on sound renal physiology, permits clinicans to focus on those patients who are most likely to overexcrete uric acid. In this subset, Emmerson’s protocol should be most useful. University of Washington,
PETER A. SIMKIN
Seattle, Washington 98195, USA
Hyperuricaemia SIR,-Professor Emmerson (June 15,
p 1461) provides an protocol for the identification of factors contributing to persistent hyperuricaemia. However, no normal ranges for plasma urate are given and the normal range for urate clearance is for a specific group of patients, the adult, mainly middle-aged, male (who, admittedly, do constitute a majority of patients with gout). Anyone investigating persistent hyperuricaemia should take into
excellent
the age and sex of the patient and the normal range for the population, since diet varies widely from country to country. The 24 h uric acid excretion on a normal diet of 70 mmol, given as an example by Emmerson, would be unusual in the UK where most people eat a low purine diet and 24 h excretion rarely exceeds 36 mmol. A more reliable measurement of uric acid handling by the kidney, which obviates any inaccuracy in urine collection,’ is the fractional uric acid excretion-ie, clearance of uric acid as a percentage of creatinine clearance. The normal mean in UK adult males with normal renal function is 82; for women it is higher at 12and in prepubertal children there is no sex difference and it is higher still at 18-5, which explains the lower plasma urate in both these groups.’ It is vital to use the appropriate yardstick. Only in this way will another underdiagnosed cause of persistent hyperuricaemia (not mentioned by Emmerson)—a familial disorder with dominant inheritance and high penetrance which untreated is associated with rapidly progressive renal disease leading to death in the 30s and 40s13-be recognised.
1. Simkin PA, Hoover PL, Paxson CS, Wilson WF. Uric acid excretion: quantitative assessment from spot, midmorning serum and urine samples. Ann Intern Med 1979; 91: 44-47. 2. Kelley WN, Palella TD. Gout and other disorders of purine metabolism In: Braunwald E, Isselbacher KJ, Petersdorf RG, Wilson JD, Martin JB, Fauci AS, eds. Principles of internal medicine, 11th ed. New York: McGraw Hill, 1987: 1623-32.
Acid-fast bacilli in
colonoscopic brushings
account
Purine Research Laboratories,
UMDS,
Guy’s Hospital, London SE1 9RT, UK
H. ANNE SIMMONDS
G, Simmonds HA, Cameron JS. Precocious familial gout with reduced fractional urate clearance and normal purine enzymes. Q J Med 1990; 277: 441-50. 2. Moro F, Ogg CS, Cameron JS, et al. Familial juvenile gouty nephropathy with renal urate hypoexcretion preceding renal disease. Clin Nephrol 1991; 35: 263-69. 3. Cameron JS, Ogg CC, Moro F, Chantler C, Simmonds HA. Precocious familial gout. Lancet 1990; 336: 745. 1. Calabrese
SIR,-Professor Emmerson’s protocol will be helpful when over excretion of uric acid is reasonably suspected. This applies, however, to a minority of hyperuricaemic patients. To justify the inconvenience of four 24 h urine collections and seven days of severe dietary restriction, there should be preliminary evidence of excessive uricosuria. We find it useful to screen hyperuricaemic patients by measuring creatinine and uric acid concentrations in an untimed, mid-morning
SiR,—Tuberculosis of the colon remains the most common cause of granulomatous colitis in India.’ Paustian and Bockus2 have laid down that one of the following criteria must be met before diagnosing abdominal tuberculosis: (1) animal inoculation or culture of suspected tissue resulting in growth of the tuberculosis organism, (2) histological demonstration of Mycobacterium tuberculosis, or (3) of tubercles with caseation necrosis, and (4) a good typical gross description of the operative fmdings with biopsy of a mesenteric lymph-node showing histological evidence of tuberculosis. Laparotomy used to be needed to meet these criteria; fibreoptic colonoscopy has circumvented that. Colonoscopic mucosal biopsy in the diagnosis of colonic tuberculosis has been questioned on the premise that the condition is submucosal and that the yield of such biopsies is likely to be low.3 Some workers take several samples from the same spot by creating a well in an attempt to reach the submucosa. Even so, acid-fast bacilli are not seen on colonoscopic biopsy in 30-50% of the reported cases, the criteria of Paustian and Bockus are difficult to meet,3,s,6 Brushings obtained at endoscopy have been extensively used to diagnose gastrointestinal malignancies7-9 but little is known about acid-fast bacilli in colonoscopic brushings. Nine consecutive patients, suspected of having abdominal tuberculosis on history, DIAGNOSTIC YIELD OF CONCENTRATION SMEAR, COLONOSCOPIC BRUSHINGS, CULTURE, AND
HISTOPATHOLOGY 0
vagal and sympathetic responses. Our work has shown that exercise training reduces the sympathetic component of the reflex in normotensive subjects without changing the sensitivity of the reflex. The method of baroreflex assessment Somers et al use suggests that exercise training increases the sensitivity of the vagal component of the reflex in borderline hypertension, but from this work it is not possible to assess the impact of training on the total reflex and on the sympathetic component in particular.
Baker Medical Research Institute, Alfred Hospital, Prahran 3181, Victoria, Australia
BRONWYN A. KINGWELL ANTHONY M. DART GARRY L. JENNINGS PAUL I. KORNER
Jennings GL, Meredith IT, Kingwell BA, Esler MD, Dart AM, Korner PI. The effect of exercise training on cardiac dimensions, sympathetic activity and the arterial baroreflex. Int Soc Hypertens 1990; S35. 2. Pickering TG, Gribbin B, Sleight P. Comparison of reflex heart rate responses to rising and falling arterial pressure in man. Cardiovasc Res 1972; 6: 277-83. 3. Smyth HS, Sleight P, Pickering GW. Reflex regulation of arterial pressure during sleep in man: a quantitative method of assessing baroreflex sensitivity. Circ Res 1.
1969; 24: 109-21. 4. Weinstock M, Komer PI, Head GA, Dorward P. Differentiation of cardiac baroreflex properties by cuff and drug methods in two rabbit strains. Am J Physiol 1988; 255: R654-64.
urine specimen and in a concurrent sample of serum.’ The product of urinary uric acid (mg/dl) and plasma creatinine (mg/dl) divided by the urinary creatinine (mg/dl) provides an assessment of uric acid excretion in mg/dl glomerular filtrate or in ml/min after the glomerular filtration rate (GFR) has been normalised to 100 ml/min. Because the urinary flow rate appears both in the calculation of the excretion rate and in the assessment of GFR by creatinine clearance, its numerical value cancels out and a timed urine collection is unnecessary. The mean in normal young men without dietary restriction is 0-40 mg/dl. I reserve more intensive evaluations for the small subset of hyperuricaemic patients whose screening values exceed 0 60 mg/dl. I agree with Kelley and Palella2 that "the most important single test in the hyperuricemic patient is analysis of the urine for uric acid." In routine practice, however, this evaluation is often neglected. The most likely explanation for this discrepancy is that many clinicians recognise both the poor precision of single, 24 h specimens and the very low yield of the test in patients selected only for hyperuricaemia. Judicious use of a screening test, based on sound renal physiology, permits clinicans to focus on those patients who are most likely to overexcrete uric acid. In this subset, Emmerson’s protocol should be most useful. University of Washington,
PETER A. SIMKIN
Seattle, Washington 98195, USA
Hyperuricaemia SIR,-Professor Emmerson (June 15,
p 1461) provides an protocol for the identification of factors contributing to persistent hyperuricaemia. However, no normal ranges for plasma urate are given and the normal range for urate clearance is for a specific group of patients, the adult, mainly middle-aged, male (who, admittedly, do constitute a majority of patients with gout). Anyone investigating persistent hyperuricaemia should take into
excellent
the age and sex of the patient and the normal range for the population, since diet varies widely from country to country. The 24 h uric acid excretion on a normal diet of 70 mmol, given as an example by Emmerson, would be unusual in the UK where most people eat a low purine diet and 24 h excretion rarely exceeds 36 mmol. A more reliable measurement of uric acid handling by the kidney, which obviates any inaccuracy in urine collection,’ is the fractional uric acid excretion-ie, clearance of uric acid as a percentage of creatinine clearance. The normal mean in UK adult males with normal renal function is 82; for women it is higher at 12and in prepubertal children there is no sex difference and it is higher still at 18-5, which explains the lower plasma urate in both these groups.’ It is vital to use the appropriate yardstick. Only in this way will another underdiagnosed cause of persistent hyperuricaemia (not mentioned by Emmerson)—a familial disorder with dominant inheritance and high penetrance which untreated is associated with rapidly progressive renal disease leading to death in the 30s and 40s13-be recognised.
1. Simkin PA, Hoover PL, Paxson CS, Wilson WF. Uric acid excretion: quantitative assessment from spot, midmorning serum and urine samples. Ann Intern Med 1979; 91: 44-47. 2. Kelley WN, Palella TD. Gout and other disorders of purine metabolism In: Braunwald E, Isselbacher KJ, Petersdorf RG, Wilson JD, Martin JB, Fauci AS, eds. Principles of internal medicine, 11th ed. New York: McGraw Hill, 1987: 1623-32.
Acid-fast bacilli in
colonoscopic brushings
account
Purine Research Laboratories,
UMDS,
Guy’s Hospital, London SE1 9RT, UK
H. ANNE SIMMONDS
G, Simmonds HA, Cameron JS. Precocious familial gout with reduced fractional urate clearance and normal purine enzymes. Q J Med 1990; 277: 441-50. 2. Moro F, Ogg CS, Cameron JS, et al. Familial juvenile gouty nephropathy with renal urate hypoexcretion preceding renal disease. Clin Nephrol 1991; 35: 263-69. 3. Cameron JS, Ogg CC, Moro F, Chantler C, Simmonds HA. Precocious familial gout. Lancet 1990; 336: 745. 1. Calabrese
SIR,-Professor Emmerson’s protocol will be helpful when over excretion of uric acid is reasonably suspected. This applies, however, to a minority of hyperuricaemic patients. To justify the inconvenience of four 24 h urine collections and seven days of severe dietary restriction, there should be preliminary evidence of excessive uricosuria. We find it useful to screen hyperuricaemic patients by measuring creatinine and uric acid concentrations in an untimed, mid-morning
SiR,—Tuberculosis of the colon remains the most common cause of granulomatous colitis in India.’ Paustian and Bockus2 have laid down that one of the following criteria must be met before diagnosing abdominal tuberculosis: (1) animal inoculation or culture of suspected tissue resulting in growth of the tuberculosis organism, (2) histological demonstration of Mycobacterium tuberculosis, or (3) of tubercles with caseation necrosis, and (4) a good typical gross description of the operative fmdings with biopsy of a mesenteric lymph-node showing histological evidence of tuberculosis. Laparotomy used to be needed to meet these criteria; fibreoptic colonoscopy has circumvented that. Colonoscopic mucosal biopsy in the diagnosis of colonic tuberculosis has been questioned on the premise that the condition is submucosal and that the yield of such biopsies is likely to be low.3 Some workers take several samples from the same spot by creating a well in an attempt to reach the submucosa. Even so, acid-fast bacilli are not seen on colonoscopic biopsy in 30-50% of the reported cases, the criteria of Paustian and Bockus are difficult to meet,3,s,6 Brushings obtained at endoscopy have been extensively used to diagnose gastrointestinal malignancies7-9 but little is known about acid-fast bacilli in colonoscopic brushings. Nine consecutive patients, suspected of having abdominal tuberculosis on history, DIAGNOSTIC YIELD OF CONCENTRATION SMEAR, COLONOSCOPIC BRUSHINGS, CULTURE, AND
HISTOPATHOLOGY 0