- Email: [email protected]
Glucose homoeostasis in young adults without diagnosis of diabetes mellitus
CORRESPONDENCE
to be developed to fight S aureusinduced endocarditis, fibrinogenbinding proteins should be considered as priority targets.
1
2
Simonetta Rindi, Stefania Cicalini, Giampiero Pietrocola, Nicola Petrosillo, *Pietro Speziale *Department of Biochemistry, University of Pavia, Viale Taramelli 3/B, 27100 Pavia, Italy; and National Institute for Infection Diseases “L Spallanzani” Rome (e-mail: [email protected]) 1
2
3
Selan L, Passariello C, Rizzo L, et al. Diagnosis of vascular graft infections with antibodies against staphylococcal slime antigens. Lancet 2002; 359: 2166–68. Colque-Navarro P, Palma M, Söderquist B, Flock J-I, Möllby R. Antibody responses in patients with staphylococcal septicemia against two Staphylococcus aureus fibrinogenbinding proteins: clumping factor and an extracellular fibrinogen-binding protein. Clin Diagn Lab Immunol 2000; 7: 14–20. Foster TJ, Höök M. Surface protein adhesins of Staphylococcus aureus. Trends Microbiol 1998; 6: 484–88.
Goosebumps and the insula Sir—J Cutts and co-workers (Aug 31, p 690)1 present an instructive case of pilomotor seizures secondary to an intracranial mass lesion. However, they do not discuss one plausible site of origin of the seizures: the insula. The right insula seems to be involved in Cutt and colleagues’ magnetic resonance image of the coronal T2weighted slice through the level of the third ventricle. Although cortical control mechanisms for autonomic functions in human beings are ill-defined,2 the insular cortex seems to have a pivotal role through its extensive reciprocal connections with temporal, limbic, and basal structures, as J Augustine3 describes. Pilomotor seizures can arise in the absence of hypothalamic pathology, and clinical evidence suggests that such seizures may have an insular (rather than mesial temporal) origin.4 Moreover, the insula is implicated in the shiver that accompanies strong emotional responses to music and other stimuli associated with powerful autonomic arousal.5 Augustine’s work3 suggests that the insula normally monitors the internal state of the organism by integrating interoceptive stimuli from various sources. Therefore, the sense of “feeling like an alien” that Cutts and colleagues’ patient described may also be attributable to insular damage. Jason Warren Wellcome Department of Imaging Neuroscience, Institute of Neurology, London WC1N 3BG, UK (e-mail: [email protected])
1978
3
4
5
Cutts J, Lee G, Berarducci M, Thomas C, Dempsey PK, Kadish SP. Goosebumps. Lancet 2002; 360: 690. Stefan H, Pauli E, Kerling F, Schwarz A, Koebnick C. Autonomic auras: left hemispheric predominance of epileptic generators of cold shivers and goose bumps? Epilepsia 2002; 43: 41–45. Augustine JR. Circuitry and functional aspects of the insular lobe in primates including humans. Brain Res Rev 1996; 22: 229–44. Lesser RP, Lüders H, Resor S. Other reports of pilomotor seizures. Neurology 1985; 35: 286–87. Blood AJ, Zatorre RJ. Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. Proc Natl Acad Sci USA 2001; 98: 11818–23.
Glucose homoeostasis in young adults without diagnosis of diabetes mellitus Sir—In their report on glucose metabolism in patients with myocardial infarction but without diagnosis of diabetes mellitus, A Norhammar and colleagues (June 22, p 2140)1 note that more than half had impaired glucose tolerance or type 2 diabetes. The patients were examined in the early phase of the acute myocardial infarction. Our findings in a case-control study in Denmark support and expand the observation.2 The study included 22 patients who had acute myocardial infarction younger than 41 years and 24 hospital-based controls with no evidence of coronary heart disease or diabetes matched for age and sex. They did not differ significantly for bodymass index and waist-to-hip ratio. Since acute myocardial infarction at a young age is rare, we selected patients diagnosed at four hospitals in Western Jutland in 1983–97. Cases and controls were examined in 1999, at least 2 years after the cases had their coronary event. No participant had a diagnosis of diabetes at examination. At that time, Denmark recommended that patients with myocardial infarction undergo assessment for secondary prevention of coronary heart disease. We did one measurement of fasting capillary whole blood glucose and of glycosylated haemoglobin (HbA1c) in each patient. Glucose concentration higher than 6·1 mmol/L and HbA1c higher than 6·1% were deemed raised. Four cases had raised glucose concentrations and seven had raised HbA1c. Overall, eight (36%) cases and five (18%) controls had impaired glucose homoeostasis. We advised these
13 participants to contact their primary physician for further assessment of impaired glucose tolerance or type 2 diabetes. Seven cases and two controls fulfilled modified criteria for the metabolic syndrome.3 According to a US recommendation, individuals older than 45 years should undergo regular assessment for impaired glucose tolerance and type 2 diabetes. We argue that patients with coronary heart disease should undergo screening for diabetes from a younger age. Norhammar and colleagues’ trial and our study support that an initial screening round can be based on measurements of fasting glucose and HbA1c, thus selecting a high-risk group for further glucose-tolerance testing. Since primary physicians undertake year-long follow-up of patients with acute myocardial infarction,4 those patients not identified by coronary care units could be given a second chance for diabetes screening in primary care— even years after the coronary event. Patients may gain from early detection of impaired glucose tolerance or asymptomatic type 2 diabetes. Individuals with impaired glucose tolerance have a 30% risk of developing type 2 diabetes within 10 years. Randomised trials from the USA and Finland consistently document that these individuals obtain a 50% reduction in risk of developing diabetes from an intervention combining a diet with little saturated fat and regular daily physical exercise. Several drugs, such as metformin and pravastatin, may also delay or reduce the progression to diabetes.5 We do not know whether the patients might obtain a synergism from combinations of pharmacological and non-pharmacological treatments. Accordingly, there is a need of further randomised studies and they may include patients with acute myocardial infarction. FEVE is a stockholder in Novo Nordisk, Denmark.
*Finn Edler von Eyben, Ejvind Mouridsen, Jan Holm, Paulius Montvilas, Georg Dimcevski Departments of *Internal Medicine, Clinical Chemistry, Radiology, and Clinical Physiology, Herning Central Hospital, DK-7400 Herning, Denmark (e-mail: [email protected]) 1
2
3
Norhammar A, Tenerz Å, Nilsson G, et al. Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study. Lancet 2002; 359: 2140–44. von Eyben FE, Mouridsen E, Holm J, et al. Smoking, low density lipoprotein cholesterol, and fibrinogen and acute myocardial infarction before 41 years of age: a Danish case-control study. J Cardiovasc Risk 2002; 9: 171–78. Alberti KGMM, Zimmet PZ, for the WHO
THE LANCET • Vol 360 • December 14, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
CORRESPONDENCE
4
5
Consultation. Definitions, diagnosis and classification of diabetes mellitus and its complications, part 1: diagnosis and classification of diabetes mellitus— provisional report of a WHO consultation. Diabetes Med 1998; 15: 539–53. Wood D, De Backer G, Faergeman O, Graham I, Mancia G, Pyörälä K. Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention. Eur Heart J 1998; 19: 1434–503. Freeman DJ, Norrie J, Sattar N, et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 2001; 103: 357–62.
Sir—Diabetes mellitus is thought of as an epidemic disease of the 21st century because of the burden resulting from vascular complications, especially cardiovascular diseases. The results of A Norhammar and colleagues1 are very impressive—only 34% of patients had normal glucose tolerance at the time of myocardial infarction. 3 months later, 25% had type 2 diabetes and 40% impaired glucose tolerance. We have reported similar results for patients with stable angina.2 We looked for disturbances in glucose metabolism in 363 Polish men with no previous diagnosis of diabetes, who had been referred for coronary angiography. We did oral glucose tolerance tests and applied the WHO criteria to diagnose diabetes or impaired glucose tolerance. 52% of patients had disturbances of glucose metabolism: 16% had type 2 diabetes and 36% impaired glucose tolerance, the latter being similar to that described by Norhammar and colleagues, although the frequency of type 2 diabetes was lower. An explanation for the difference could be the lower mean age among our patients (mean 52·9 [SD 9·1] vs 63·5 years [9·4]), since age is a known risk factor for type 2 diabetes, or the lower fasting plasma glucose criteria (>6·0 mmol/L) used by Norhammar and colleagues. If we take into account impaired fasting glucose (glucose concentration 6·1–7·0 mmol/L), 37 individuals fulfilled these criteria, but 16 had been previously diagnosed as having type 2 diabetes and 15 as having impaired glucose tolerance. If we classify the 21 patients with newly identified impaired fasting glucose as having type 2 diabetes, the frequency of diabetes would be 22%. However, in our study, the mean HbA1c value was higher than that in Norhammar and colleagues’ study (5·9 [0·7] vs 5·0% 0·6]), despite the lower prevalence of diabetes, yet Norhammar and colleagues concluded that HbA1c concentration at admission
was predictive of a type 2 diabetes diagnosis. The most important issue highlighted in these two studies is the importance of post-load glycaemia in diagnosing disturbances of glucose metabolism. Norhammar and colleagues report that when the fasting blood glucose criteria were applied, only about 10% of individuals were diagnosed as having diabetes. Our results would be almost the same if we included the patients with impaired fasting glucose as having type 2 diabetes. Otherwise 98·3% of diabetic patients were diagnosed on the basis of post-load glycaemia. *Irina Kowalska, Ida Kinalska, Beata Telejko
with conservative measures, including glyceryl trinitrate ointment and botulinum injection. Our experience suggests that the development of ulceration in association with the use of nicorandil might be an indicator of the severity of ischaemic heart disease and could reflect poor perfusion of this area. *Mark Vella, Richard G Molloy Department of Surgical Gastroenterology, Gartnavel General Hospital, Great Western Road, Glasgow G12 0YN, UK (e-mail: [email protected]) 1
Watson A, Al Ozairi O, Fraser A, Loudon M, O’Kelly T. Nicorandil associated anal ulceration. Lancet 2002; 360: 546–47.
Department of Endocrinology, Diabetology and Internal Medicine, Medical Academy in Biatystok, 15-276 Biatystok, Poland (e-mail: [email protected])
Tobacco money: up in smoke?
1
Sir—Steven Woloshin and colleagues1 criticise the New York Early Lung Cancer Action Project (NY-ELCAP) (June 15, p 2108). As participants involved in a major consortium to coordinate research efforts into detection of early lung cancer in Europe and the USA, we feel that their remarks were misdirected. A consensus statement issued from a major lung cancer screening conference strongly recommended rapid assessment of spiral CT for lung cancer screening.2 The National Cancer Institute (NCI) and American Cancer Society (ACS) have intensively explored this issue through expert workshops. A consensus was that the observational studies, such as ELCAP, have been crucial in providing approaches to the clinical management of case work-up, intervention, and Although workshop follow-up.3 attendees supported the importance of doing randomised controlled trials to address the question of efficacy, they also acknowledged the ongoing role of observational investigations. In the detection of much smaller primary lesions, the increased sensitivity of spiral CT is changing every aspect of lung cancer management. With the potential for overdiagnosis in mind, researchers are focusing on efficient and less morbid clinical management approaches. To distinguish clinically important from benign nodules, the Cornell group has used three-dimensional image processing to reconstruct the shape of the nodules, allowing measurement of nodule growth through time.4 The pace of development with spiral CT scanners, moving from single detector arrays to four to 16 arrays, is occurring
2
Norhammar A, Tenerz A, Nilsson G, et al. Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study. Lancet 2002; 359: 2140–44. Kowalska I, Prokop J, Bachórzewska-Gajewska H, et al. Disturbances of glucose metabolism in men referred for coronary arteriography: postload glycemia as a predictor of coronary atherosclerosis. Diabetes Care 2001; 24: 897–901.
Nicorandil-associated anal ulceration Sir—Like Angus Watson and colleagues (Aug 17, p 546),1 we have noted an association between severe anal ulceration and the use of nicorandil. In two patients, the ulceration developed spontaneously, whereas a third patient developed anal ulceration after elective excision of symptomatic skin tags. In each patient, the ulceration progressed rapidly to encompass up to half the circumference of the anal canal. Clinically, the ulcers had indolent overhanging skin edges and scanty granulation tissue. Histological examination revealed no specific features. All three patients (two men aged 76 and 86 years, and one woman aged 66 years) had severe ischaemic heart disease. Although all patients were taking nicorandil at the time of presentation (30 mg twice daily in two patients, and 20 mg twice daily in the other), the association with anal ulceration had not been made and this drug was not therefore discontinued. All three progressively deteriorated with respect to cardiovascular status and died within 6 months of presentation. Their ulcers failed to heal
THE LANCET • Vol 360 • December 14, 2002 • www.thelancet.com
1979
For personal use. Only reproduce with permission from The Lancet Publishing Group.
to be developed to fight S aureusinduced endocarditis, fibrinogenbinding proteins should be considered as priority targets.
1
2
Simonetta Rindi, Stefania Cicalini, Giampiero Pietrocola, Nicola Petrosillo, *Pietro Speziale *Department of Biochemistry, University of Pavia, Viale Taramelli 3/B, 27100 Pavia, Italy; and National Institute for Infection Diseases “L Spallanzani” Rome (e-mail: [email protected]) 1
2
3
Selan L, Passariello C, Rizzo L, et al. Diagnosis of vascular graft infections with antibodies against staphylococcal slime antigens. Lancet 2002; 359: 2166–68. Colque-Navarro P, Palma M, Söderquist B, Flock J-I, Möllby R. Antibody responses in patients with staphylococcal septicemia against two Staphylococcus aureus fibrinogenbinding proteins: clumping factor and an extracellular fibrinogen-binding protein. Clin Diagn Lab Immunol 2000; 7: 14–20. Foster TJ, Höök M. Surface protein adhesins of Staphylococcus aureus. Trends Microbiol 1998; 6: 484–88.
Goosebumps and the insula Sir—J Cutts and co-workers (Aug 31, p 690)1 present an instructive case of pilomotor seizures secondary to an intracranial mass lesion. However, they do not discuss one plausible site of origin of the seizures: the insula. The right insula seems to be involved in Cutt and colleagues’ magnetic resonance image of the coronal T2weighted slice through the level of the third ventricle. Although cortical control mechanisms for autonomic functions in human beings are ill-defined,2 the insular cortex seems to have a pivotal role through its extensive reciprocal connections with temporal, limbic, and basal structures, as J Augustine3 describes. Pilomotor seizures can arise in the absence of hypothalamic pathology, and clinical evidence suggests that such seizures may have an insular (rather than mesial temporal) origin.4 Moreover, the insula is implicated in the shiver that accompanies strong emotional responses to music and other stimuli associated with powerful autonomic arousal.5 Augustine’s work3 suggests that the insula normally monitors the internal state of the organism by integrating interoceptive stimuli from various sources. Therefore, the sense of “feeling like an alien” that Cutts and colleagues’ patient described may also be attributable to insular damage. Jason Warren Wellcome Department of Imaging Neuroscience, Institute of Neurology, London WC1N 3BG, UK (e-mail: [email protected])
1978
3
4
5
Cutts J, Lee G, Berarducci M, Thomas C, Dempsey PK, Kadish SP. Goosebumps. Lancet 2002; 360: 690. Stefan H, Pauli E, Kerling F, Schwarz A, Koebnick C. Autonomic auras: left hemispheric predominance of epileptic generators of cold shivers and goose bumps? Epilepsia 2002; 43: 41–45. Augustine JR. Circuitry and functional aspects of the insular lobe in primates including humans. Brain Res Rev 1996; 22: 229–44. Lesser RP, Lüders H, Resor S. Other reports of pilomotor seizures. Neurology 1985; 35: 286–87. Blood AJ, Zatorre RJ. Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. Proc Natl Acad Sci USA 2001; 98: 11818–23.
Glucose homoeostasis in young adults without diagnosis of diabetes mellitus Sir—In their report on glucose metabolism in patients with myocardial infarction but without diagnosis of diabetes mellitus, A Norhammar and colleagues (June 22, p 2140)1 note that more than half had impaired glucose tolerance or type 2 diabetes. The patients were examined in the early phase of the acute myocardial infarction. Our findings in a case-control study in Denmark support and expand the observation.2 The study included 22 patients who had acute myocardial infarction younger than 41 years and 24 hospital-based controls with no evidence of coronary heart disease or diabetes matched for age and sex. They did not differ significantly for bodymass index and waist-to-hip ratio. Since acute myocardial infarction at a young age is rare, we selected patients diagnosed at four hospitals in Western Jutland in 1983–97. Cases and controls were examined in 1999, at least 2 years after the cases had their coronary event. No participant had a diagnosis of diabetes at examination. At that time, Denmark recommended that patients with myocardial infarction undergo assessment for secondary prevention of coronary heart disease. We did one measurement of fasting capillary whole blood glucose and of glycosylated haemoglobin (HbA1c) in each patient. Glucose concentration higher than 6·1 mmol/L and HbA1c higher than 6·1% were deemed raised. Four cases had raised glucose concentrations and seven had raised HbA1c. Overall, eight (36%) cases and five (18%) controls had impaired glucose homoeostasis. We advised these
13 participants to contact their primary physician for further assessment of impaired glucose tolerance or type 2 diabetes. Seven cases and two controls fulfilled modified criteria for the metabolic syndrome.3 According to a US recommendation, individuals older than 45 years should undergo regular assessment for impaired glucose tolerance and type 2 diabetes. We argue that patients with coronary heart disease should undergo screening for diabetes from a younger age. Norhammar and colleagues’ trial and our study support that an initial screening round can be based on measurements of fasting glucose and HbA1c, thus selecting a high-risk group for further glucose-tolerance testing. Since primary physicians undertake year-long follow-up of patients with acute myocardial infarction,4 those patients not identified by coronary care units could be given a second chance for diabetes screening in primary care— even years after the coronary event. Patients may gain from early detection of impaired glucose tolerance or asymptomatic type 2 diabetes. Individuals with impaired glucose tolerance have a 30% risk of developing type 2 diabetes within 10 years. Randomised trials from the USA and Finland consistently document that these individuals obtain a 50% reduction in risk of developing diabetes from an intervention combining a diet with little saturated fat and regular daily physical exercise. Several drugs, such as metformin and pravastatin, may also delay or reduce the progression to diabetes.5 We do not know whether the patients might obtain a synergism from combinations of pharmacological and non-pharmacological treatments. Accordingly, there is a need of further randomised studies and they may include patients with acute myocardial infarction. FEVE is a stockholder in Novo Nordisk, Denmark.
*Finn Edler von Eyben, Ejvind Mouridsen, Jan Holm, Paulius Montvilas, Georg Dimcevski Departments of *Internal Medicine, Clinical Chemistry, Radiology, and Clinical Physiology, Herning Central Hospital, DK-7400 Herning, Denmark (e-mail: [email protected]) 1
2
3
Norhammar A, Tenerz Å, Nilsson G, et al. Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study. Lancet 2002; 359: 2140–44. von Eyben FE, Mouridsen E, Holm J, et al. Smoking, low density lipoprotein cholesterol, and fibrinogen and acute myocardial infarction before 41 years of age: a Danish case-control study. J Cardiovasc Risk 2002; 9: 171–78. Alberti KGMM, Zimmet PZ, for the WHO
THE LANCET • Vol 360 • December 14, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
CORRESPONDENCE
4
5
Consultation. Definitions, diagnosis and classification of diabetes mellitus and its complications, part 1: diagnosis and classification of diabetes mellitus— provisional report of a WHO consultation. Diabetes Med 1998; 15: 539–53. Wood D, De Backer G, Faergeman O, Graham I, Mancia G, Pyörälä K. Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention. Eur Heart J 1998; 19: 1434–503. Freeman DJ, Norrie J, Sattar N, et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 2001; 103: 357–62.
Sir—Diabetes mellitus is thought of as an epidemic disease of the 21st century because of the burden resulting from vascular complications, especially cardiovascular diseases. The results of A Norhammar and colleagues1 are very impressive—only 34% of patients had normal glucose tolerance at the time of myocardial infarction. 3 months later, 25% had type 2 diabetes and 40% impaired glucose tolerance. We have reported similar results for patients with stable angina.2 We looked for disturbances in glucose metabolism in 363 Polish men with no previous diagnosis of diabetes, who had been referred for coronary angiography. We did oral glucose tolerance tests and applied the WHO criteria to diagnose diabetes or impaired glucose tolerance. 52% of patients had disturbances of glucose metabolism: 16% had type 2 diabetes and 36% impaired glucose tolerance, the latter being similar to that described by Norhammar and colleagues, although the frequency of type 2 diabetes was lower. An explanation for the difference could be the lower mean age among our patients (mean 52·9 [SD 9·1] vs 63·5 years [9·4]), since age is a known risk factor for type 2 diabetes, or the lower fasting plasma glucose criteria (>6·0 mmol/L) used by Norhammar and colleagues. If we take into account impaired fasting glucose (glucose concentration 6·1–7·0 mmol/L), 37 individuals fulfilled these criteria, but 16 had been previously diagnosed as having type 2 diabetes and 15 as having impaired glucose tolerance. If we classify the 21 patients with newly identified impaired fasting glucose as having type 2 diabetes, the frequency of diabetes would be 22%. However, in our study, the mean HbA1c value was higher than that in Norhammar and colleagues’ study (5·9 [0·7] vs 5·0% 0·6]), despite the lower prevalence of diabetes, yet Norhammar and colleagues concluded that HbA1c concentration at admission
was predictive of a type 2 diabetes diagnosis. The most important issue highlighted in these two studies is the importance of post-load glycaemia in diagnosing disturbances of glucose metabolism. Norhammar and colleagues report that when the fasting blood glucose criteria were applied, only about 10% of individuals were diagnosed as having diabetes. Our results would be almost the same if we included the patients with impaired fasting glucose as having type 2 diabetes. Otherwise 98·3% of diabetic patients were diagnosed on the basis of post-load glycaemia. *Irina Kowalska, Ida Kinalska, Beata Telejko
with conservative measures, including glyceryl trinitrate ointment and botulinum injection. Our experience suggests that the development of ulceration in association with the use of nicorandil might be an indicator of the severity of ischaemic heart disease and could reflect poor perfusion of this area. *Mark Vella, Richard G Molloy Department of Surgical Gastroenterology, Gartnavel General Hospital, Great Western Road, Glasgow G12 0YN, UK (e-mail: [email protected]) 1
Watson A, Al Ozairi O, Fraser A, Loudon M, O’Kelly T. Nicorandil associated anal ulceration. Lancet 2002; 360: 546–47.
Department of Endocrinology, Diabetology and Internal Medicine, Medical Academy in Biatystok, 15-276 Biatystok, Poland (e-mail: [email protected])
Tobacco money: up in smoke?
1
Sir—Steven Woloshin and colleagues1 criticise the New York Early Lung Cancer Action Project (NY-ELCAP) (June 15, p 2108). As participants involved in a major consortium to coordinate research efforts into detection of early lung cancer in Europe and the USA, we feel that their remarks were misdirected. A consensus statement issued from a major lung cancer screening conference strongly recommended rapid assessment of spiral CT for lung cancer screening.2 The National Cancer Institute (NCI) and American Cancer Society (ACS) have intensively explored this issue through expert workshops. A consensus was that the observational studies, such as ELCAP, have been crucial in providing approaches to the clinical management of case work-up, intervention, and Although workshop follow-up.3 attendees supported the importance of doing randomised controlled trials to address the question of efficacy, they also acknowledged the ongoing role of observational investigations. In the detection of much smaller primary lesions, the increased sensitivity of spiral CT is changing every aspect of lung cancer management. With the potential for overdiagnosis in mind, researchers are focusing on efficient and less morbid clinical management approaches. To distinguish clinically important from benign nodules, the Cornell group has used three-dimensional image processing to reconstruct the shape of the nodules, allowing measurement of nodule growth through time.4 The pace of development with spiral CT scanners, moving from single detector arrays to four to 16 arrays, is occurring
2
Norhammar A, Tenerz A, Nilsson G, et al. Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study. Lancet 2002; 359: 2140–44. Kowalska I, Prokop J, Bachórzewska-Gajewska H, et al. Disturbances of glucose metabolism in men referred for coronary arteriography: postload glycemia as a predictor of coronary atherosclerosis. Diabetes Care 2001; 24: 897–901.
Nicorandil-associated anal ulceration Sir—Like Angus Watson and colleagues (Aug 17, p 546),1 we have noted an association between severe anal ulceration and the use of nicorandil. In two patients, the ulceration developed spontaneously, whereas a third patient developed anal ulceration after elective excision of symptomatic skin tags. In each patient, the ulceration progressed rapidly to encompass up to half the circumference of the anal canal. Clinically, the ulcers had indolent overhanging skin edges and scanty granulation tissue. Histological examination revealed no specific features. All three patients (two men aged 76 and 86 years, and one woman aged 66 years) had severe ischaemic heart disease. Although all patients were taking nicorandil at the time of presentation (30 mg twice daily in two patients, and 20 mg twice daily in the other), the association with anal ulceration had not been made and this drug was not therefore discontinued. All three progressively deteriorated with respect to cardiovascular status and died within 6 months of presentation. Their ulcers failed to heal
THE LANCET • Vol 360 • December 14, 2002 • www.thelancet.com
1979
For personal use. Only reproduce with permission from The Lancet Publishing Group.