- Email: [email protected]
Reversible Huntington's Disease—lesion to the globus pallidus?
CORRESPONDENCE
sepsis, especially with respect to the high negative predictive value. *E Esra Önal, F Kitapçi, U Dilmen, B Adam Divisions of *Neonatology and Biochemistry and Clinical Chemistry, Fatih University Medical School, Ankara, Turkey 1
2
3
Küster H, Weiss M, Willeitner AE, et al. Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation. Lancet 1998; 352: 1271–77. Doellner H, Arntzen KJ, Haereid PE, Aag S, Austgulen R. Interleukin-6 concentrations in neonates evaluated for sepsis. J Pediatr 1998; 132: 295–99. Buck C, Bundschu J, Gallati H, et al. Interleukin-6: a sensitive parameter for the early diagnosis of neonatal bacterial infection. Pediatrics 1994; 93: 54–58.
described as delay. In aerodigestive cancer the disease can reach an advanced stage before symptoms are apparent. The silent period can extend to stage IV. The situation has been static for 40 years and will remain so until biological markers are identified that make selective screening a realistic proposition. Mark McGurk Department of Oral and Maxillofacial Surgery, Guy’s Hospital, London SE1 9RT, UK 1
2
3
Socioeconomic status and bowel cancer Sir—The evidence that M V Ionescu and colleagues (Oct 31, p 1439)1 provide that low socioeconomic groups are more likely to present with advanced cancer of the bowel suggests that the delay in diagnosis is due to under use of health care facilities by deprived individuals. The explanation is probably correct as a coarse-grain analysis, but a fine-grain picture is more complicated. Squamous cell carcinoma of the upper alimentary tract is predominately a disease of lower socioeconomic groups (with some notable exceptions), and in our analysis (1961–97) of 480 patients about half had greater than 3 months delay from symptom recognition to diagnosis, with a similar percentage presenting with advanced disease; but these two groups were not the same set of patients because there was no correlation between delay and stage of disease at diagnosis. These proportions have remained the same over a period of roughly 40 years despite the obvious resources made available to the health service since 1960:
1956–65 1966–75 1976–85 1992–97
Delayed diagnosis
Advanced disease
47% 56% 53% 48%
47% 48% 35% 54%
Data for 1986–91 not complete.
A lack of correlation between delay and stage has been noted in lung, upper gastrointestinal, and bowel cancer.2–5 Delay has two components; a silent, presymptomatic period from tumour inception to symptom recognition and a postsymptomatic period commonly
240
4
5
Ionescu MV, Carey F, Tait IS, Steele RJC. Socio-economic status and stage at presentation of colorectal cancer. Lancet 1998; 352: 1439. Robinson E, Mohilever J, Zindan J, Sapir D. Delay in diagnosis of cancer. Possible effect on stage of the disease and survival. Cancer 1984; 54: 1454–60. Porta M, Gallen M, Malats N, Planas J. Influence of diagnostic delay upon cancer survival: an analysis of five tumour stites. J Epidemiol Commun Hlth 1991; 45: 225–30. Martin I, Young S, Sue-Ling H, Johnson D. Delays in the diagnosis of oesophagogastric cancer: a consecutive case series. BMJ 1997; 314: 467–71. Vineis P, Fornero G, Magnino A, Giacometti R, Ciccone G. Diagnostic delay, clinical stage and social class: a hospital based study. J Epidemiol Commun Hlth 1993; 47: 229–31.
globus pallidus ameliorated the behavioural and neurodegenerative effects of lesions to the striatum by quinolinic acid lesion (an animal model for Huntington’s disease) of the striatum. Bonelli shows two magnetic resonance imaging scans of the patient—one from 1991 and one from 1996—that show increased atrophy of the caudate. However, since the cuts in the two scans differ slightly, it is difficult to assess whether there was also degeneration of the globus pallidus during that period. Perhaps this possibility can be assessed from an examination of both complete scans. If indeed this patient had degeneration of the globus pallidus along with that of caudate, it might give further impetus to examine lesioning as treatment for Huntington’s disease, an established notion for treatment of Parkinson’s disease—for example, pallidotomy. Eric Lewin Altschuler School of Medicine and Brain and Perception Laboratory, University of California at San Diego, La Jolla, CA 92093, USA (e-mail: [email protected]) 1
2
Reversible Huntington’s Disease—lesion to the globus pallidus? Sir—Raphael Bonelli and colleagues (Nov 7, p 1520)1 describe a remarkable case of possibly reversible Huntington’s disease. The patient presented at age 63 years in 1991 with chorea. Subsequent genetic testing, done twice, showed that the patient had 42 [CAG]n-repeats in the gene associated with Huntington’s disease (the cutoff for disease is >38 repeats). The patient was placed on cyanamide, dosulepin, and diazepam without improvement. He was readmitted in 1992 and his medications were changed to tiapride, citalopram, and diazepam, with slight improvement in symptoms. His condition eventually worsened and he was admitted for the third time in January, 1996. His medications were changed to haloperidol and mianserin and his symptoms improved. The patient is reported to have been free of chorea for 31 months and even returned to skiing. Bonelli and colleagues attribute the patient’s improvement not to a change in medication, but, rather, possibly to degeneration of another brain area after degeneration of the caudate. Where might the other lesion be? I suggest this lesion might be in the globus pallidus. Interestingly, Joel and colleagues2 showed that lesion to the
Bonelli R, Költringer P, Kenner L, Reisecher F. Reversible Huntington’s disease? Lancet 1998; 352: 1520–21. Joel D, Ayalon L, Tarrasch R, Veenman L, Feldon J, Weiner I. Electrolytic lesion of globus pallidus ameliorates the behavioural and neurodegenerative effects of quinolinic acid lesion of the striatum: a potential novel treatment in a rat model of Huntington’s disease. Brain Res 1998; 787: 143–48.
Authors’ reply Sir—We agree with Eric Altschuler that a stereotactic lesion in the globus pallidus could ameliorate the choreatic symptoms caused by striatal degeneration. Indeed, there is evidence to indicate that patients with hemiballism and dystonia (symptoms closely linked to chorea) may benefit from globus pallidus internus pallidotomy,1 although the underlying mechanism is as yet unclear. Moreover, Joel and colleagues,2 cited by Altschuler, reported that in the rat model of Huntington’s disease, stereotactic lesions in the globus pallidus externus may ameliorate the behavioural performance in the animal model and might even slow down the progressive striatal degeneration. Given these findings, we would put the globus pallidus in concrete terms, although we believe that the degeneration of other basal ganglia structures could also have caused the cessation of Huntington’s disease chorea in our patient. But this is not the place to go into further detail. However, the current model of basal ganglia function is unable to explain the beneficial effects of pallidotomy in hyperkinetic movement disorders.
THE LANCET • Vol 353 • January 16, 1999
CORRESPONDENCE
According to this model, globus pallidus internus is one of the major basal ganglia output nuclei.3 Globus pallidus internus exerts a tonic GABAergic inhibitory effect on the ventrolateral motor thalamus. Destruction of the inhibitory structure would, according to this model, induce an excess of excitatory influences on the frontocortical regions such as the motor cortex, which would result in a hyperkinetic syndrome rather than ameliorating it. In agreement with this model, globus pallidus internus is currently used as a target for treatment of hypokinetic movement disorders as seen in Parkinson’s disease.3 Since patients with hyperkinetic movement disorders including dystonia and hemiballism can also benefit from globus pallidus internus pallidotomy,1 recent reports emphasise the insufficiency of the current model of basal ganglia organisation.4 In fact, the most constant benefit observed after lesions of the posteroventral globus pallidus internus is a reduction of L-dopa-induced dyskinesias,5 an occurrence not explicable by the current model. Dysfunctional patterns of activity rather than the rate of neuronal firing in the globus pallidus have been implicated in the genesis of hypokinetic and hyperkinetic movement disorders. In turn, abolishing this aberrant pattern of activity by globus pallidus internus pallidotomy could account for the beneficial effects of this procedure in the setting of hypokinetic and hyperkinetic movement disorder.1 With respect to our patient, cranial MRI scans obtained in 1991 and 1996 did not show globus pallidus internus and globus pallidus externus lesions. To definitively solve this intriguing question, we need new MRI scans of our patient so that we can closely scrutinise possible basal ganglia alterations. These examinations are currently in progress and this important discussion can be continued only with those results. *Raphael M Bonelli, Andreas Gruber, Lukas Kenner, Peter Költringer, Franz Reisecker *Department of Neurology and Psychiatry, Hospital BHB Eggenberg, 8021 Graz, Austria; Department of Neurosurgery, University of Vienna, Vienna; and Department of Pathology, University of Graz, Graz 1
2
Suarez JI, Metman LV, Reich SG, et al. Pallidotomy for hemiballism: efficacy and characteristics of neuronal activity. Ann Neurol 1997; 42: 807–11. Joel D, Ayalon L, Tarrasch R, et al. electrolytic lesion of globus pallidus ameliorates the behavioural and neurodegenerative effects of quinolinic acid lesion of the striatum: a potential novel treatment in a rat model of Huntington’s disease. Brain Res 1998; 787: 143–48.
THE LANCET • Vol 353 • January 16, 1999
3
4
5
Alexander GE. Basal ganglia— thalamocortical circuits: their role in control of movements. J Clin Neurophysiol 1994; 11: 420–31. Parent A, Cicchetti F. The current model of basal ganglia organisation under scrutiny. Mov Disord 1998; 13: 199–202. Dogali M, Fazzini E, Koldony E, et al. Stereotactic ventral pallidotomy for Parkinson’s disease. Neurology 1995; 45: 753–61.
HIV vaccine: how long must we wait? Sir—In your Oct 24 editorial1 you focus on the shortcomings of the US National Institute of Health (NIH) and somewhat miss the mark. Although the NIH is certainly far from perfect, it is the world and the global public health effort that has got it wrong about the urgent need for an HIV vaccine, not NIH. NIH has consistently been and still is the most active world funder of activities to design and develop an HIV vaccine. The International AIDS Vaccine initiative (IAVI) blueprint makes the empirical argument eloquently that we must move ahead post-haste with all plausible approaches on many fronts worldwide. NIH, like IAVI, is also currently trying to develop new mechanisms for bridging the gap between basic research and product development. The answer to your question, how long must we wait, is not simply a question of how much the US NIH spends and who is in charge, Most of the early candidates have not advanced because they have not been promising—a normal and healthy part of scientific exploration. The world needs a concerted effort on behalf of governments, private foundations, and pharmaceutical companies to overcome the scientific and political challenges to developing an HIV vaccine. Bill Snow AIDS Vaccine Advocacy Coalition, Washington, DC 20009, USA 1
Editorial. An HIV vaccine: how long must we wait? Lancet 1998; 352: 1323.
Sir—Your editorial1 rightly points out that funding for HIV vaccines is poor, partly because the prospects of success for any of the non-replicating candidate vaccines is bleak. It also stems from the fears that any living vaccines would be, potentially at least, too dangerous to use on a large scale. Nonetheless, nef deletion mutants of simian immunodeficiency virus have shown great promise as effective vaccines in monkeys: preventing disease in immunised animals, challenged with
homologous or heterologous virus, either cell associated or cell free, by the mucosal or the blood stream route of infection. Moreover, HIV carrying a nef deletion has also been found to be poorly if at all pathogenic for man. The time would seem to be right for a Lancet conference on HIV vaccines. Even if a sufficiently attenuated vaccine cannot be derived, it should be possible to eludicate the mechanism of immunity conferred by the attenuated vaccine in the monkey model as a means to improve the prospects for the development of a non-replicating vaccine. John Beale The Priest’s House, Sissinghurst Castle, Cranbrook, Kent TN17 2AR, UK 1
Editorial. An HIV vaccine: how long must we wait? Lancet 1998; 352: 1323.
Antibiotic resistance in Helicobacter pylori Sir—The report by A A van Zwet and co-workers (Nov 14, p1595)1 of a stable resistance to amoxicillin in Helicobacter pylori challenges the previous, optimistic view that this was a rare event2 and also constitutes a source of great concern. Antibiotic resistance in H pylori is a growing problem2,3 that requires community surveillance of the germ sensitivity to antibacterial agents and, possibly, susceptibility testing before the start of eradication therapy.1,2 A cautionary note must be made against the rising trend that favours indiscriminate eradication of H pylori, not only in patients with peptic ulcers or in severe conditions such as low-grade mucosa-associated lymphoid tissue lymphoma,4 but also in other gastroduodenal disorders and extragastric diseases. Particularly important is the issue of functional dyspepsia, a benign disorder that affects at least 25% of the population, of which up to 60% of cases also have H pylori infection.4 Even the final report of The Maastricht Consensus Conference, defined as advisable eradication of H pylori infection in dyspeptic patients with no endoscopic evidence of peptic ulceration or other gastroduodenal mucosal abnormalities.4 On the basis of the available clinical trials, the efficacy of eradication therapy in functional dyspepsia is questionable.5 Nevertheless, also because of the ambiguity of these guidelines, the practice of eradication of H pylori in dyspeptic patients is increasing, and leads to widespread use of antibiotics, even when unnecessary. Antibiotic
241
sepsis, especially with respect to the high negative predictive value. *E Esra Önal, F Kitapçi, U Dilmen, B Adam Divisions of *Neonatology and Biochemistry and Clinical Chemistry, Fatih University Medical School, Ankara, Turkey 1
2
3
Küster H, Weiss M, Willeitner AE, et al. Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation. Lancet 1998; 352: 1271–77. Doellner H, Arntzen KJ, Haereid PE, Aag S, Austgulen R. Interleukin-6 concentrations in neonates evaluated for sepsis. J Pediatr 1998; 132: 295–99. Buck C, Bundschu J, Gallati H, et al. Interleukin-6: a sensitive parameter for the early diagnosis of neonatal bacterial infection. Pediatrics 1994; 93: 54–58.
described as delay. In aerodigestive cancer the disease can reach an advanced stage before symptoms are apparent. The silent period can extend to stage IV. The situation has been static for 40 years and will remain so until biological markers are identified that make selective screening a realistic proposition. Mark McGurk Department of Oral and Maxillofacial Surgery, Guy’s Hospital, London SE1 9RT, UK 1
2
3
Socioeconomic status and bowel cancer Sir—The evidence that M V Ionescu and colleagues (Oct 31, p 1439)1 provide that low socioeconomic groups are more likely to present with advanced cancer of the bowel suggests that the delay in diagnosis is due to under use of health care facilities by deprived individuals. The explanation is probably correct as a coarse-grain analysis, but a fine-grain picture is more complicated. Squamous cell carcinoma of the upper alimentary tract is predominately a disease of lower socioeconomic groups (with some notable exceptions), and in our analysis (1961–97) of 480 patients about half had greater than 3 months delay from symptom recognition to diagnosis, with a similar percentage presenting with advanced disease; but these two groups were not the same set of patients because there was no correlation between delay and stage of disease at diagnosis. These proportions have remained the same over a period of roughly 40 years despite the obvious resources made available to the health service since 1960:
1956–65 1966–75 1976–85 1992–97
Delayed diagnosis
Advanced disease
47% 56% 53% 48%
47% 48% 35% 54%
Data for 1986–91 not complete.
A lack of correlation between delay and stage has been noted in lung, upper gastrointestinal, and bowel cancer.2–5 Delay has two components; a silent, presymptomatic period from tumour inception to symptom recognition and a postsymptomatic period commonly
240
4
5
Ionescu MV, Carey F, Tait IS, Steele RJC. Socio-economic status and stage at presentation of colorectal cancer. Lancet 1998; 352: 1439. Robinson E, Mohilever J, Zindan J, Sapir D. Delay in diagnosis of cancer. Possible effect on stage of the disease and survival. Cancer 1984; 54: 1454–60. Porta M, Gallen M, Malats N, Planas J. Influence of diagnostic delay upon cancer survival: an analysis of five tumour stites. J Epidemiol Commun Hlth 1991; 45: 225–30. Martin I, Young S, Sue-Ling H, Johnson D. Delays in the diagnosis of oesophagogastric cancer: a consecutive case series. BMJ 1997; 314: 467–71. Vineis P, Fornero G, Magnino A, Giacometti R, Ciccone G. Diagnostic delay, clinical stage and social class: a hospital based study. J Epidemiol Commun Hlth 1993; 47: 229–31.
globus pallidus ameliorated the behavioural and neurodegenerative effects of lesions to the striatum by quinolinic acid lesion (an animal model for Huntington’s disease) of the striatum. Bonelli shows two magnetic resonance imaging scans of the patient—one from 1991 and one from 1996—that show increased atrophy of the caudate. However, since the cuts in the two scans differ slightly, it is difficult to assess whether there was also degeneration of the globus pallidus during that period. Perhaps this possibility can be assessed from an examination of both complete scans. If indeed this patient had degeneration of the globus pallidus along with that of caudate, it might give further impetus to examine lesioning as treatment for Huntington’s disease, an established notion for treatment of Parkinson’s disease—for example, pallidotomy. Eric Lewin Altschuler School of Medicine and Brain and Perception Laboratory, University of California at San Diego, La Jolla, CA 92093, USA (e-mail: [email protected]) 1
2
Reversible Huntington’s Disease—lesion to the globus pallidus? Sir—Raphael Bonelli and colleagues (Nov 7, p 1520)1 describe a remarkable case of possibly reversible Huntington’s disease. The patient presented at age 63 years in 1991 with chorea. Subsequent genetic testing, done twice, showed that the patient had 42 [CAG]n-repeats in the gene associated with Huntington’s disease (the cutoff for disease is >38 repeats). The patient was placed on cyanamide, dosulepin, and diazepam without improvement. He was readmitted in 1992 and his medications were changed to tiapride, citalopram, and diazepam, with slight improvement in symptoms. His condition eventually worsened and he was admitted for the third time in January, 1996. His medications were changed to haloperidol and mianserin and his symptoms improved. The patient is reported to have been free of chorea for 31 months and even returned to skiing. Bonelli and colleagues attribute the patient’s improvement not to a change in medication, but, rather, possibly to degeneration of another brain area after degeneration of the caudate. Where might the other lesion be? I suggest this lesion might be in the globus pallidus. Interestingly, Joel and colleagues2 showed that lesion to the
Bonelli R, Költringer P, Kenner L, Reisecher F. Reversible Huntington’s disease? Lancet 1998; 352: 1520–21. Joel D, Ayalon L, Tarrasch R, Veenman L, Feldon J, Weiner I. Electrolytic lesion of globus pallidus ameliorates the behavioural and neurodegenerative effects of quinolinic acid lesion of the striatum: a potential novel treatment in a rat model of Huntington’s disease. Brain Res 1998; 787: 143–48.
Authors’ reply Sir—We agree with Eric Altschuler that a stereotactic lesion in the globus pallidus could ameliorate the choreatic symptoms caused by striatal degeneration. Indeed, there is evidence to indicate that patients with hemiballism and dystonia (symptoms closely linked to chorea) may benefit from globus pallidus internus pallidotomy,1 although the underlying mechanism is as yet unclear. Moreover, Joel and colleagues,2 cited by Altschuler, reported that in the rat model of Huntington’s disease, stereotactic lesions in the globus pallidus externus may ameliorate the behavioural performance in the animal model and might even slow down the progressive striatal degeneration. Given these findings, we would put the globus pallidus in concrete terms, although we believe that the degeneration of other basal ganglia structures could also have caused the cessation of Huntington’s disease chorea in our patient. But this is not the place to go into further detail. However, the current model of basal ganglia function is unable to explain the beneficial effects of pallidotomy in hyperkinetic movement disorders.
THE LANCET • Vol 353 • January 16, 1999
CORRESPONDENCE
According to this model, globus pallidus internus is one of the major basal ganglia output nuclei.3 Globus pallidus internus exerts a tonic GABAergic inhibitory effect on the ventrolateral motor thalamus. Destruction of the inhibitory structure would, according to this model, induce an excess of excitatory influences on the frontocortical regions such as the motor cortex, which would result in a hyperkinetic syndrome rather than ameliorating it. In agreement with this model, globus pallidus internus is currently used as a target for treatment of hypokinetic movement disorders as seen in Parkinson’s disease.3 Since patients with hyperkinetic movement disorders including dystonia and hemiballism can also benefit from globus pallidus internus pallidotomy,1 recent reports emphasise the insufficiency of the current model of basal ganglia organisation.4 In fact, the most constant benefit observed after lesions of the posteroventral globus pallidus internus is a reduction of L-dopa-induced dyskinesias,5 an occurrence not explicable by the current model. Dysfunctional patterns of activity rather than the rate of neuronal firing in the globus pallidus have been implicated in the genesis of hypokinetic and hyperkinetic movement disorders. In turn, abolishing this aberrant pattern of activity by globus pallidus internus pallidotomy could account for the beneficial effects of this procedure in the setting of hypokinetic and hyperkinetic movement disorder.1 With respect to our patient, cranial MRI scans obtained in 1991 and 1996 did not show globus pallidus internus and globus pallidus externus lesions. To definitively solve this intriguing question, we need new MRI scans of our patient so that we can closely scrutinise possible basal ganglia alterations. These examinations are currently in progress and this important discussion can be continued only with those results. *Raphael M Bonelli, Andreas Gruber, Lukas Kenner, Peter Költringer, Franz Reisecker *Department of Neurology and Psychiatry, Hospital BHB Eggenberg, 8021 Graz, Austria; Department of Neurosurgery, University of Vienna, Vienna; and Department of Pathology, University of Graz, Graz 1
2
Suarez JI, Metman LV, Reich SG, et al. Pallidotomy for hemiballism: efficacy and characteristics of neuronal activity. Ann Neurol 1997; 42: 807–11. Joel D, Ayalon L, Tarrasch R, et al. electrolytic lesion of globus pallidus ameliorates the behavioural and neurodegenerative effects of quinolinic acid lesion of the striatum: a potential novel treatment in a rat model of Huntington’s disease. Brain Res 1998; 787: 143–48.
THE LANCET • Vol 353 • January 16, 1999
3
4
5
Alexander GE. Basal ganglia— thalamocortical circuits: their role in control of movements. J Clin Neurophysiol 1994; 11: 420–31. Parent A, Cicchetti F. The current model of basal ganglia organisation under scrutiny. Mov Disord 1998; 13: 199–202. Dogali M, Fazzini E, Koldony E, et al. Stereotactic ventral pallidotomy for Parkinson’s disease. Neurology 1995; 45: 753–61.
HIV vaccine: how long must we wait? Sir—In your Oct 24 editorial1 you focus on the shortcomings of the US National Institute of Health (NIH) and somewhat miss the mark. Although the NIH is certainly far from perfect, it is the world and the global public health effort that has got it wrong about the urgent need for an HIV vaccine, not NIH. NIH has consistently been and still is the most active world funder of activities to design and develop an HIV vaccine. The International AIDS Vaccine initiative (IAVI) blueprint makes the empirical argument eloquently that we must move ahead post-haste with all plausible approaches on many fronts worldwide. NIH, like IAVI, is also currently trying to develop new mechanisms for bridging the gap between basic research and product development. The answer to your question, how long must we wait, is not simply a question of how much the US NIH spends and who is in charge, Most of the early candidates have not advanced because they have not been promising—a normal and healthy part of scientific exploration. The world needs a concerted effort on behalf of governments, private foundations, and pharmaceutical companies to overcome the scientific and political challenges to developing an HIV vaccine. Bill Snow AIDS Vaccine Advocacy Coalition, Washington, DC 20009, USA 1
Editorial. An HIV vaccine: how long must we wait? Lancet 1998; 352: 1323.
Sir—Your editorial1 rightly points out that funding for HIV vaccines is poor, partly because the prospects of success for any of the non-replicating candidate vaccines is bleak. It also stems from the fears that any living vaccines would be, potentially at least, too dangerous to use on a large scale. Nonetheless, nef deletion mutants of simian immunodeficiency virus have shown great promise as effective vaccines in monkeys: preventing disease in immunised animals, challenged with
homologous or heterologous virus, either cell associated or cell free, by the mucosal or the blood stream route of infection. Moreover, HIV carrying a nef deletion has also been found to be poorly if at all pathogenic for man. The time would seem to be right for a Lancet conference on HIV vaccines. Even if a sufficiently attenuated vaccine cannot be derived, it should be possible to eludicate the mechanism of immunity conferred by the attenuated vaccine in the monkey model as a means to improve the prospects for the development of a non-replicating vaccine. John Beale The Priest’s House, Sissinghurst Castle, Cranbrook, Kent TN17 2AR, UK 1
Editorial. An HIV vaccine: how long must we wait? Lancet 1998; 352: 1323.
Antibiotic resistance in Helicobacter pylori Sir—The report by A A van Zwet and co-workers (Nov 14, p1595)1 of a stable resistance to amoxicillin in Helicobacter pylori challenges the previous, optimistic view that this was a rare event2 and also constitutes a source of great concern. Antibiotic resistance in H pylori is a growing problem2,3 that requires community surveillance of the germ sensitivity to antibacterial agents and, possibly, susceptibility testing before the start of eradication therapy.1,2 A cautionary note must be made against the rising trend that favours indiscriminate eradication of H pylori, not only in patients with peptic ulcers or in severe conditions such as low-grade mucosa-associated lymphoid tissue lymphoma,4 but also in other gastroduodenal disorders and extragastric diseases. Particularly important is the issue of functional dyspepsia, a benign disorder that affects at least 25% of the population, of which up to 60% of cases also have H pylori infection.4 Even the final report of The Maastricht Consensus Conference, defined as advisable eradication of H pylori infection in dyspeptic patients with no endoscopic evidence of peptic ulceration or other gastroduodenal mucosal abnormalities.4 On the basis of the available clinical trials, the efficacy of eradication therapy in functional dyspepsia is questionable.5 Nevertheless, also because of the ambiguity of these guidelines, the practice of eradication of H pylori in dyspeptic patients is increasing, and leads to widespread use of antibiotics, even when unnecessary. Antibiotic
241