OBJECTIVE—To investigate, by thallium-201 scanning, circulation in the muscles of the lower limb (LL) in diabetic patients without clinical peripheral vascular disease but with a high cardiovascular risk profile.

RESEARCH DESIGN AND METHODS—A total of 80 diabetic patients (76 patients with type 2 diabetes, mean age 57.3 years, duration of diabetes 13.0 ± 7.5 years) with more than one additional cardiovascular risk factor but no claudication were investigated. After stress testing, 1.5 MBq/kg thallium-201 was administered to perform myocardial single-photon emission computed tomography followed by LL scanning. Muscle blood flow was considered abnormal if the asymmetry in thallium-201 uptake between the two buttocks and/or thighs and/or calves was >10%.

RESULTS—Muscle perfusion defects were found in 42% of the patients, mainly in the calves. These defects correlated with retinopathy (P = 0.042) and the HbA1c level (P = 0.044). In patients with defects in the buttock and/or thigh, the prevalence of nephropathy and retinopathy was higher than in those with isolated defects in the calf (P = 0.032 and 0.023, respectively).

CONCLUSIONS—This study suggests that LL scanning coupled with myocardial scintigraphy is a convenient method of investigating peripheral muscle circulation. Proximal perfusion defects in patients without clinical arterial disease are associated with increased prevalence of retinopathy and nephropathy and, therefore, may be due to microvascular disease of LL muscle. Distal defects may indicate silent macrovascular disease of the LL.

After 38 years of follow-up, the Framingham Heart Study showed that the risk of developing intermittent claudication was increased by associated coronary heart disease and diabetes (1). The prevalence of coronary artery disease and peripheral vascular disease (PVD) is high in the diabetic population (2,3). More than 50% of diabetic patients die from cardiovascular diseases (4), and the morbidity due to PVD is very high (5). Furthermore, claudication is, in turn, a strong predictor of subsequent cardiovascular events (6,7,8).

In diabetic patients with other risk factors, myocardial scintigraphy is suggestive of silent myocardial ischemia (SMI) in 20–30% of cases (9). These patients commonly have angiographically normal coronary arteries and endothelial dysfunction, and myocardial microvascular changes are involved (10). Whole-body exercise thallium-201 (201Tl) scintigraphy, performed after stress testing, permits detection of early functional abnormalities of lower-limb (LL) vascularization (11,12,13,14,15,16,17,18,19). Furthermore, this test investigates not only macrovascular but also microvascular blood flow (12,19).

We performed myocardial 201Tl scintigraphy after stress testing to detect SMI in a selected population of diabetic patients without claudication and without cardiac symptoms and signs but with a high cardiovascular risk profile. We took this opportunity to perform LL scanning. In particular, we examined the prevalence of LL perfusion abnormalities and the factors associated with these abnormalities, including the results of the myocardial scanning.

Patients

A total of 80 patients (44 men, 36 women) were prospectively recruited in the Department of Diabetology of Jean Verdier Hospital (Bondy, France). Mean age was 57.3 years (range 36–77). Four patients had type 1 diabetes and 76 patients had type 2 diabetes that was treated by diet and oral hypoglycemic drugs or insulin. The duration of disease was ≥15 years in the patients with type 1 diabetes and ≥5 years in the patients with type 2 diabetes. The mean duration of diabetes was 13 years (range 5–36). The criteria for inclusion were absence of myocardial infarction or angina pectoris, normal results of 12-lead resting electrocardiography (ECG), and absence of claudication. In seven patients, one foot pulse was not palpable. In these seven patients, an LL arterial ultrasound examination was performed to ensure that no PVD was present. Results were normal in four patients and showed slight irregularities of the femoral or tibial arteries in the three others. No carotid or femoral murmur was heard in any of the patients. None of the patients had a history of stroke. All patients had at least one additional cardiovascular risk factor: dyslipidemia (serum total cholesterol >6.5 mmol/l and/or triglycerides >2.3 mmol/l and/or lipid-lowering treatment), hypertension (blood pressure >140/80 mmHg or antihypertensive treatment), past or current use of tobacco (>10 pack-years of cigarette exposure), or urinary albumin excretion rate >30 mg/day.

None of the patients had congenital heart disease or cardiomyopathy, asthma or severe chronic bronchopathy, renal failure with plasma creatinine >250 μmol/l, thyroid disease, chronic alcohol consumption, or trauma/surgery involving the LL.

Presence of diabetic retinopathy was assessed by an experienced ophthalmologist through dilated pupils by direct ophthalmoscopy and fluorescein angiography. Diabetic retinopathy was diagnosed if at least one microaneurysm, hemorrhage, or exudate in one eye was observed. The condition was classified as nonproliferative in 21 patients (14 mild, 1 moderate, 6 very severe) and proliferative in 3 patients (20). The presence of nephropathy, defined by an albumin excretion rate >30 mg/day on at least two assessments, was diagnosed in 20 patients, including 4 patients with clinical albuminuria (>300 mg/day) (21). Evidence of neuropathy was obtained on the basis of at least one objective sign (including absence of both ankle tendon reflexes and impairment of LL touch and pin-prick sensation), whether or not the patient had symptoms (22). The baseline data of the patients are summarized in Table 1.

Myocardial scintigraphy

Stress 201Tl myocardial scintigraphy was performed on all patients. Briefly, ECG was performed during graded exercise testing on a bicycle ergometer. The workload from an initial level of 30 W was increased by 30 W every 3 min. Cardiac rhythm was monitored continuously, 12-lead ECG was performed, and arterial blood pressure was measured at baseline and at the end of each work load. The results of the test were considered positive if angina pectoris occurred or if there was an ST-segment horizontal or downsloping depression ≥0.1 mV at 0.08 s beyond the J point, ventricular ectopic activity, atrioventricular blockade, or intraventricular bundle blockade. The results of exercise ECG were interpreted as negative if there were no ischemic changes during exercise and the patient achieved >85% of the maximum predicted heart rate. At the near-maximal peak of exercise, 1.5 MBq/kg 201Tl was administered, and exercise was continued for 1 min more. Single-photon emission computed tomography (SPECT) imaging was performed within 5–10 min after the injection of 201Tl, with the patient in the supine position, using a single-head, wide-angle-lens gamma camera (Sophycamera DSX Rectangular; SMV, Buc, France) and a low-energy, high-resolution collimator. Delayed images were obtained 4 ± 0.5 h later. The perfusion pattern in each vascular territory was assessed as normal or showing stable or reversible abnormalities (23). SMI was defined by positive results of ECG stress testing and/or exercise myocardial SPECT.

LL scintigraphy

Patients were instructed to remain in the supine position for LL 201Tl scanning in the same run after exercise myocardial SPECT imaging, <35 min after peak exercise. A single 512 × 512 pixel posterior pass was used with a scanning speed of 15 cm/min (11). Data were again stored on a magnetic disk linked to a SOPHY NXT/P workstation (SMV, Buc, France). Three irregular areas of interest were drawn using a trackball around the entire buttock, thigh, and calf on one side. Symmetrical areas of interest were automatically generated (Fig. 1). No correction was made for background activity. Total counts in each of the three levels were then determined by computer, and right-to-left ratios were calculated at each level. A ratio <0.9 or >1.1 at one or several levels defined an abnormal result of LL scintigraphy for the level considered, as reported previously (11). The perfusion defects were obvious in some patients, but counting was always performed.

Coronary angiography

For patients with SMI, cardiac catheterization was proposed. Left heart catheterization and coronary arteriography were performed by the percutaneous femoral approach. Coronary angiograms were analyzed by two experienced investigators. Patients were considered to have coronary artery disease if coronary stenosis was ≥50% in the left coronary artery or ≥70% in the left anterior descending artery, the circumflex artery, a well-developed marginal vessel, or the right coronary artery.

Biological measurements

The following measurements were recorded: HbA1c (integration of the electrophoretic peak; Hyrys Hydrasys, Sebia, France; normal value <6%), serum total cholesterol and triglycerides, HDL cholesterol (enzymatic colorimetry; Hitachi 912; Roche-Boehringer, Meylan, France), plasma creatinine (kinetic colorimetry; Kone, Helsinki, Finland), and the 24-h urinary albumin excretion rate (laser immunonephelometry; BN100; Dade-Behring, Paris la Défense, France) were measured.

Statistical analysis

The statistical analyses were performed using SPSS software (SPSS, Chicago, IL). The continuous data were expressed as means ± SD, and the correlations with the scintigraphy variable were tested by the Mann-Whitney nonparametric test. The various qualitative predictive information was crosstabulated with the scintigraphy variable, and the correlations were tested by the Pearson’s χ2 test or the Fisher’s exact test. All P values were two-sided; a value <0.05 was considered statistically significant.

SMI

According to the results of exercise myocardial scintigraphy, 17 patients (21.2%) had SMI. None of these patients experienced angina pectoris during the test. Coronary angiography was performed in 14 of these patients (3 refused) and significant coronary stenoses were shown in 9 patients. SMI was significantly more frequent in men than in women (34.0 vs. 5.5%, P = 0.002) and in patients with neuropathy (32.6 vs. 17.6%, P = 0.012).

LL 201Tl scintigraphy

Two examples are shown in Fig. 1. Mean total counts of each level, and regional right-to-left ratios are shown in Table 2. A one-level abnormality was found in 29 patients, a two-level abnormality was found in 2 patients, and a three-level abnormality was found in 2 patients. The abnormalities were most commonly found on the calves (23 patients). The abnormalities were unilateral (14 on the right LL and 18 on the left LL), except in one patient, who had an abnormality of the right thigh as well as the left buttock. Therefore, LL 201Tl scanning was abnormal in 33 patients.

Factors associated with abnormal results of LL scanning

The univariate correlates of the positive results of LL 201Tl scanning were a high level of HbA1c (P = 0.044) and the presence of retinopathy (P = 0.042) (Table 3). Of the 33 patients with an abnormal result of LL scintigraphy, 10 patients (30.3%) had abnormal results of myocardial scanning. Of these 10 patients, coronary angiography was performed in 8 patients; significant coronary stenoses were shown in 6 patients and normal coronary arteries were shown in 2 patients. Of the 47 patients with normal results of LL scanning, 7 patients (14.9%) had abnormal results of myocardial scanning. One patient refused the coronary angiography, three patients had significant coronary stenoses, and three patients had normal coronary arteries. An abnormal result of myocardial 201Tl scintigraphy did not correlate significantly with an abnormal result of LL scintigraphy (P = 0.097).

Influence of the localization of the abnormal results of LL 201Tl scanning

The patients were separated into three groups. Group 1 consisted of the 47 patients with normal results of LL scanning. Group 2 consisted of the 13 patients with proximal (buttock and/or thigh levels) asymmetry of the LL perfusion but no abnormality at the calf level (these patients were considered not to have a macrovascular disease). Group 3 consisted of the 20 patients with isolated abnormal perfusion of the calf (Table 4). The prevalence of nephropathy differed significantly between the three groups (P = 0.016) and was significantly higher in group 2 (53.8%) than in group 1 (23.4%) (P = 0.032). There was a similar trend for retinopathy (P = 0.065), the prevalence of which was higher in group 2 (53.8%) than in group 1 (21.3%) (P = 0.023).

LL scanning methods and clinical validation

Arteriography is the gold standard for diagnosing occlusive arterial disease of the legs. It provides morphological data but no information about flow, which depends on the amount of exercise, the collateral circulation, and the presence of small-vessel disease. Furthermore, this test is invasive. 201Tl is a potassium analog that has many of the physical characteristics of potassium. Its distribution within the skeletal muscle reflects the fractional distribution of cardiac output and is related to regional blood flow (24). Regional 201Tl uptake in the LL is studied after exercise (11,12,13,14,15,16,19), as in myocardial perfusion studies. The reproducibility is high (15). Two methods are available: the first consists of scanning the whole body and comparing LL thallium activity with whole-body activity (11,12,14,15,16,19). Using this method, Segall et al. (11) compared patients with angiographically proved PVD and age-matched men without PVD. They showed that this method had a sensitivity of 100% (11). However, specificity was only 10%, and young men without PVD had to be used as control subjects to reach a specificity of 71% (11). To overcome that point, the second method has been used. It consists of measuring the regional 201Tl uptake in the LL and calculating the right-to-left side intraindividual ratio (11,12,13,16,19). The physiological differences related to sex, age, weight, and physical training are then avoided (11). Tellier (12) studied a control population of 54 healthy male subjects with a mean age of 54 years and found an abnormal ratio after stress (defined by two SD over the mean value) for buttocks, thighs, and calves of 1.120, 1.078, and 1.084, respectively (12). The ratios were 1.04 and 1.2 for thighs and calves, respectively, when Seder et al. studied 11 healthy young men (16). A ratio <0.9 or >1.1 was considered by Segall et al. (11) to be abnormal. Indeed, such a ratio at one or several levels (buttocks, thighs, or calves) afforded a sensitivity of 81% for PVD detection as shown by angiography or a Doppler ankle-brachial index <1.0 (11). Using a control population of young men or age-matched men, the specificity was 83 and 80%, respectively (11).

LL scanning results

In the present study, we demonstrated abnormal results of LL 201Tl scanning in 42% of diabetic patients with a high cardiovascular risk profile. These abnormalities suggest peripheral vascular disorders at a silent stage, because they were found in asymptomatic patients who were able to reach the maximal theoretic heart rate during the stress testing. The prevalence of abnormal results of LL scintigraphy was twice the prevalence of SMI. This is in good agreement with the results of Tellier (12), who performed the same investigations in a population with proven coronary artery disease and in a group of smokers (19). As reported before (12,13,16,19), the lesions were essentially distal.

Evaluating both microvascular and macrovascular disease

Abnormal results of LL 201Tl scanning might have been expected to be associated with coronary stenoses in the patients with SMI. Such association was not found (P = 0.097), but further investigation is needed in a larger series. LL perfusion abnormalities may result not only from macrovascular disease but also from microvascular disorders. The fact that the occurrence of proximal perfusion defects without distal defects is associated with a higher prevalence of nephropathy and retinopathy is in agreement with microvascular disorders. Because we have previously found evidence for endothelial dysfunction and a reduction in coronary reserve due to microvascular changes in diabetic patients with SMI but angiographically normal coronary arteries (10), we may hypothesize that such factors might be involved in the patients with an abnormal result of LL scanning but without significant peripheral artery lesions. Therefore, femoral endothelial dysfunction has also been demonstrated in type 2 diabetic patients (25). Endothelial dysfunction might also contribute to the decrease in muscle 201Tl uptake by interfering with distal vasomotricity. Although microvascular disease is likely to be bilateral, our findings suggest that, as in the eye, the disease may be asymmetrically distributed.

In conclusion, the present study using LL 201Tl scintigraphy coupled with exercise in diabetic patients with other cardiovascular risk factors but no claudication shows evidence of defective peripheral blood flow in 42% of cases. Further study is needed to clarify whether this disorder is mainly related to macrovascular or microcirculatory dysfunction. Abnormal results of LL scanning correlated with poorer glycemic control and microangiopathic complications, which suggests that they might account for microvascular disease. The cost of LL imaging during myocardial scintigraphy is low because it requires only some additional time. Early scintigraphic detection of functional vascular abnormalities and their location and extent should lead to early and preventive management. Prospective studies are mandatory to evaluate the usefulness of early detection of PVD and its putative predictive value for more severe angiopathic lesions and complications.

Figure 1 —

Examples of LL 201Tl scintigraphy. A: Patient with a normal result of LL 201Tl scanning (posterior view). The right-to-left ratios for buttocks, thighs, and calves were 0.99, 0.98, and 0.97, respectively. B: Patient with an abnormal result of LL 201Tl scanning. The right-to-left ratios for buttocks, thighs, and calves were 0.96, 0.92, and 0.63, respectively. The test showed a defect of perfusion in the right calf (arrow).

Figure 1 —

Examples of LL 201Tl scintigraphy. A: Patient with a normal result of LL 201Tl scanning (posterior view). The right-to-left ratios for buttocks, thighs, and calves were 0.99, 0.98, and 0.97, respectively. B: Patient with an abnormal result of LL 201Tl scanning. The right-to-left ratios for buttocks, thighs, and calves were 0.96, 0.92, and 0.63, respectively. The test showed a defect of perfusion in the right calf (arrow).

Close modal
Table 1 —

Clinical and biological parameters in the 80 diabetic patients

Clinical parameters 
 Sex ratio (male/female) 44/36 
 Age (years) 57.3 ± 9.5 
 BMI (kg/m228.5 ± 5.7 
Diabetes 
 Type (1/2)  4/76 
 Insulin treatment 12 (15) 
 Duration (years) 13.0 ± 7.6 
 HbA1c (%)  8.8 ± 2.2 
 Retinopathy 24 (30) 
 Nephropathy 20 (25) 
 Neuropathy 43 (53.8) 
Other risk factors 
 Dyslipidemia 33 (41) 
 Hypertension 42 (52.5) 
 Tobacco use 28 (35) 
Clinical parameters 
 Sex ratio (male/female) 44/36 
 Age (years) 57.3 ± 9.5 
 BMI (kg/m228.5 ± 5.7 
Diabetes 
 Type (1/2)  4/76 
 Insulin treatment 12 (15) 
 Duration (years) 13.0 ± 7.6 
 HbA1c (%)  8.8 ± 2.2 
 Retinopathy 24 (30) 
 Nephropathy 20 (25) 
 Neuropathy 43 (53.8) 
Other risk factors 
 Dyslipidemia 33 (41) 
 Hypertension 42 (52.5) 
 Tobacco use 28 (35) 

Data are means ± SD or n (%).

Table 2 —

Regional results of the LL 201TI scintigraphy

Buttock levelThigh levelCalf level
Mean right total count/min 58,473 ± 20,399 56,078 ± 19,919 40,842 ± 14,209 
Mean left total count/min 58,587 ± 20,279 56,065 ± 21,217 39,815 ± 12,595 
Mean right-to-left total count ratio 1.001 1.011 1.019 
Patients with ratio <0.9 (right defect) 4 (5) 2 (2.5) 9 (11.25) 
Patients with ratio >1.1 (left defect) 5 (6.25) 5 (6.25) 14 (17.5) 
Total number of patients with an abnormal ratio 9 (11.25) 7 (8.75) 23 (28.75) 
Buttock levelThigh levelCalf level
Mean right total count/min 58,473 ± 20,399 56,078 ± 19,919 40,842 ± 14,209 
Mean left total count/min 58,587 ± 20,279 56,065 ± 21,217 39,815 ± 12,595 
Mean right-to-left total count ratio 1.001 1.011 1.019 
Patients with ratio <0.9 (right defect) 4 (5) 2 (2.5) 9 (11.25) 
Patients with ratio >1.1 (left defect) 5 (6.25) 5 (6.25) 14 (17.5) 
Total number of patients with an abnormal ratio 9 (11.25) 7 (8.75) 23 (28.75) 

Data are means ± SD or n (%).

Table 3 —

Clinical and biological correlates of the abnormal results of LL scanning

Normal scintigraphyAbnormal scintigraphyP value
n 47 33 
Sex (M/F) 23/24 21/12 0.193 
Age (years) 58.4 ± 9.2 56.6 ± 10.1 0.389 
BMI (kg/m228.7 ± 6.2 28.2 ± 5.1 0.728 
Duration of diabetes (years) 12.1 ± 8.0 14.3 ± 7.0 0.204 
HbA1c (%) 8.4 ± 2.2 9.4 ± 2 0.044 
Retinopathy 10 (21.3) 14 (42.4) 0.042 
Nephropathy 11 (23.4) 9 (27.3) 0.694 
Creatinine clearance (ml/min) 92.2 ± 27.4 87.6 ± 28.6 0.471 
Neuropathy 22 (46.8) 21 (63.6) 0.137 
Tobacco use 13 (27.7) 15 (45.5) 0.100 
Hypertension 24 (51.1) 18 (54.5) 0.759 
Dyslipidemia 21 (44.7) 12 (36.4) 0.457 
Silent myocardial ischemia 7 (14.9) 10 (30.3) 0.097 
Abnormal coronary arteriography 3 (6.5) 6 (19.4) 0.145 
Normal scintigraphyAbnormal scintigraphyP value
n 47 33 
Sex (M/F) 23/24 21/12 0.193 
Age (years) 58.4 ± 9.2 56.6 ± 10.1 0.389 
BMI (kg/m228.7 ± 6.2 28.2 ± 5.1 0.728 
Duration of diabetes (years) 12.1 ± 8.0 14.3 ± 7.0 0.204 
HbA1c (%) 8.4 ± 2.2 9.4 ± 2 0.044 
Retinopathy 10 (21.3) 14 (42.4) 0.042 
Nephropathy 11 (23.4) 9 (27.3) 0.694 
Creatinine clearance (ml/min) 92.2 ± 27.4 87.6 ± 28.6 0.471 
Neuropathy 22 (46.8) 21 (63.6) 0.137 
Tobacco use 13 (27.7) 15 (45.5) 0.100 
Hypertension 24 (51.1) 18 (54.5) 0.759 
Dyslipidemia 21 (44.7) 12 (36.4) 0.457 
Silent myocardial ischemia 7 (14.9) 10 (30.3) 0.097 
Abnormal coronary arteriography 3 (6.5) 6 (19.4) 0.145 

Data are means ± SD or n (%).

Table 4 —

Clinical and biological correlates of the results of LL scanning considering the localization of the perfusion abnormalities

Group 1Group 2Group 3P value
n 47 13 20 
Sex (M/F) 23/24 8/5 13/7 0.421 
Age (years) 58.4 ± 9.2 53.9 ± 10.0 61.4 ± 9.1 0.668 
BMI (kg/m228.7 ± 6.2 26.5 ± 4.5 29.4 ± 5.2 0.341 
Duration of diabetes (years) 12.1 ± 8.0 16.5 ± 8.2 12.8 ± 5.9 0.172 
HbA1c (%) 8.4 ± 2.2 8.9 ± 1.8 9.7 ± 2.1 0.074 
Retinopathy 10 (21.3) 7 (53.8)  7 (35.0) 0.065 
Nephropathy 11 (23.4) 7 (53.8)  2 (10.0) 0.016 
Creatinine clearance (ml/min) 92.2 ± 27.4 89.0 ± 27.7 86.7 ± 29.9 0.752 
Neuropathy 22 (46.8) 8 (61.5) 13 (65.0) 0.325 
Tobacco use 13 (27.7) 5 (38.5) 10 (50.0) 0.206 
Hypertension 24 (51.1) 7 (53.8) 11 (55.0) 0.952 
Dyslipidemia 21 (44.7) 3 (23.1)  9 (45.0) 0.347 
Silent myocardial ischemia  7 (14.9) 4 (30.8)  6 (30.0) 0.252 
Abnormal coronarography  3 (6.5)  3 (25.0)  3 (15.8) 0.196 
Group 1Group 2Group 3P value
n 47 13 20 
Sex (M/F) 23/24 8/5 13/7 0.421 
Age (years) 58.4 ± 9.2 53.9 ± 10.0 61.4 ± 9.1 0.668 
BMI (kg/m228.7 ± 6.2 26.5 ± 4.5 29.4 ± 5.2 0.341 
Duration of diabetes (years) 12.1 ± 8.0 16.5 ± 8.2 12.8 ± 5.9 0.172 
HbA1c (%) 8.4 ± 2.2 8.9 ± 1.8 9.7 ± 2.1 0.074 
Retinopathy 10 (21.3) 7 (53.8)  7 (35.0) 0.065 
Nephropathy 11 (23.4) 7 (53.8)  2 (10.0) 0.016 
Creatinine clearance (ml/min) 92.2 ± 27.4 89.0 ± 27.7 86.7 ± 29.9 0.752 
Neuropathy 22 (46.8) 8 (61.5) 13 (65.0) 0.325 
Tobacco use 13 (27.7) 5 (38.5) 10 (50.0) 0.206 
Hypertension 24 (51.1) 7 (53.8) 11 (55.0) 0.952 
Dyslipidemia 21 (44.7) 3 (23.1)  9 (45.0) 0.347 
Silent myocardial ischemia  7 (14.9) 4 (30.8)  6 (30.0) 0.252 
Abnormal coronarography  3 (6.5)  3 (25.0)  3 (15.8) 0.196 

Data are means ± SD or n (%). Group 1: patients with normal results of LL 201TI scanning; group 2: patients with proximal (buttocks and/or thighs) abnormalities; group 3: patients with only calf abnormalities.

We thank Sandrine Perret for secretarial assistance and Marion Sutton-Attali for assistance with the English manuscript.

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Address correspondence and reprint requests to Emmanuel Cosson, MD, Department of Endocrinology-Diabetology-Nutrition, Hospital Jean Verdier, Avenue du 14 juillet, Paris Bondy Cedex 93143, France. E-mail: emmanuel.cosson@jvr.ap-hop-paris.fr.

Received for publication 15 August 2000 and accepted in revised form 16 January 2001.

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.