CORRESPONDENCE 4 Singh S, Wig N, Chaudhary D, Sood NK, Sharma BK. Changing pattern of acute poisoning in adults: experience of a large North-West Indian hospital. J Assoc Phys India 1997; 45: 194–97. 3 4 Herpes encephalitis Sir—The magnetic resonance (MR) Clinical picture, published in the Oct 26 issue (p 1286),1 showed predominantly right temporal lobe involvement with herpes encephalitis in a patient with altered mental status and fever. However, the scan shown was not a T2-weighted image with gadolinium, as stated by the authors, but a fluid-attenuated inversionrecovery (FLAIR) image with gadolinium (also referred to as contrast-enhanced FLAIR image). On FLAIR images, as seen in this case, the signal from cerebrospinal fluid is suppressed and becomes dark, by contrast with a very bright appearance on T2-weighted images. FLAIR MR sequences have become essential in assessment of brain lesions, because of their high sensitivity, which generally surpasses T2-weighted images, especially in areas adjacent to cerebrospinal fluid-containing spaces.2 The high signal seen in the apex of the fourth ventricle in the presented case is a flow-related artifact, typically seen on FLAIR images. Furthermore, T2-weighted sequences are generally not used with gadolinium, since they do not provide contrast enhancement; perfusion MRI uses specially designed dynamic postcontrast T2-weighted sequences, on which, by contrast, a loss of signal is seen with accumulation of gadolinium.3 For a time, contrast-enhanced FLAIR images were increasingly popular, and early reports suggested they could even replace contrastenhanced T1-weighted images. However, results of a recent study4 showed that FLAIR images with gadolinium have lower sensitivity and specificity than standard contrastenhanced T1-weighted images. Evidence is accumulating that diffusion-weighted images, known for their reliability in acute stroke assessment, seem to be more sensitive than FLAIR images for detection of herpes encephalitis.5 Zoran Rumboldt Department of Radiology, University Hospital “Sisters of Mercy”, Vinogradska 29, Zagreb, HR 10000, Croatia (e-mail: [email protected]) 1 2 Martin K, Franco-Paredes C. Herpes encephalitis. Lancet 2002; 360: 1286 Okuda T, Korogi Y, Shigematsu Y, et al. Brain lesions: when should fluid-attenuated 260 5 inversion-recovery sequences be used in brain evaluation? Radiology 1999; 212: 793–98. Lev M, Rosen B. Clinical applications of intracranial perfusion MR imaging. Neuroimaging Clin N Am 1999; 9: 309–31. Singh SK, Leeds NE, Ginsberg LE. MR imaging of leptomeningeal metastases: comparison of three sequences. AmJ Neuroradiol 2002; 23: 817–21. Teixeira J, Zimmerman RA, Haselgrove JC, Bilaniuk LT, Hunter JV. Diffusion imaging in pediatric central nervous system infections. Neuroradiology 2001; 43: 1031–39. event”, or that “an individual’s sociological milieu is responsible for his or her cancer”. Ultimately, Shuter’s criticisms of Thabet and colleagues do not convince, because he chooses to undermine sound scientific evidence to further his own agenda. Martin Sidis Adan Hospital, Ministry of Health, Kuwait (e-mail: [email protected]) 1 2 Emotional problems of Palestinian children living in a war zone Sir—Jonathan Shuter (Oct 5, p 1098)1 commits a serious error in his use of junk science (faulty scientific analysis to further a special agenda). He criticises Abdel Aziz Mousa Thabet and colleagues2 for inferring causality from a cross-sectional analysis in their study of Palestinian children living in war zones. He also disputes the investigators’ findings that children’s emotional responses to exposure to political violence are acute and severe. Shuter argues that this finding is not justified because it is similar to “the conclusion that low-calorie drinks cause obesity, since many obese people drink these beverages”. Shuter’s objections prompt me to ask, are we making the same sort of mistake in cross-sectional studies of smoking and lung cancer, when we say that smoking causes lung cancer, because many patients with lung cancer are smokers? Next, Shuter suggests that Palestinian children’s emotional problems are caused by “the educational, political, religious, and social environment in which are raised”. To use the same analogy, if I said that “the educational, political, religious, and social environment in which human beings are raised causes emotional problems and this leads to lung cancer, but not the smoking” would The Lancet publish my letter? Shuter goes on to reject Thabet and colleagues’ comparison of children exposed to home bombardment and demolition with a control group. Shuter maintains that such demolition “is not a random event” since many of the homes that were destroyed “were bomb factories or munitions depots”. Again, Shuter’s contention is exactly as absurd as saying that “those exposed to smoking who developed lung cancer were already harbouring cancer, and this was not a random Shuter J. Emotional problems in Palestinian children living in a war zone. Lancet 2002; 360: 1098. Thabet AAM, Abed Y, Vostanis P. Emotional problems in Palestinian children living in a war zone: a crosssectional study. Lancet 2002; 359: 1801–04. Ocular tuberculosis Sir—Volker Grosse and colleagues (Sept 21, p 922)1 describe a 30-year-old Gambian man who presented with a constellation of symptoms and signs that suggested a differential diagnosis of systemic tuberculosis in addition to metastatic carcinoma and lymphoma. Obtaining ocular tissue for definitive diagnostic purpose is associated with a significant ocular morbidity. Therefore, a high degree of clinical suspicion is the key to early diagnosis. Instead of enucleating a vital sense organ like the eye, I feel that the authors should have done a biopsy of an easily accessible site such as the cervical lymph node to demonstrate the characteristic findings of caseating granuloma and Mycobacterium tuberculosis. The effectiveness of antituberculosis treatment has obviated the need for operative intervention in tuberculomas and tuberculous abscesses, except when decompression is required to prevent permanent neurological deficits. Furthermore, unlike other bacterial abscesses, tuberculous abscesses do not necessarily require drainage.2 When patients with tuberculosis elsewhere in the body develop clinical features of ocular involvement, the treatment of ocular tuberculosis is along the same lines as treatment of pulmonary tuberculosis.3 Therefore, instead of a hurried enucleation, the patient described by Grosse and colleagues could have been given a chance to preserve the right eye pending followup assessment after antituberculosis treatment. Another important point is that retobulbar optic neuritis and the resultant amblyopia are the most frequent and serious adverse effects of ethambutol treatment.4 Symptoms include blurred vision, central THE LANCET • Vol 361 • January 18, 2003 • www.thelancet.com For personal use. Only reproduce with permission from The Lancet Publishing Group. CORRESPONDENCE scotomas, and red-green colour blindness. The visual symptoms precede a measurable loss of visual acuity. This complication is dose-related and occurs in less than 1% of patients given a daily dose of 15 mg/kg, and increases with a daily dose of 25 mg/kg.3 Ocular toxicity induced by antituberculosis treatment should have been an important consideration when starting drugs. Grosse and colleagues, having enucleated one eye, could have chosen a more appropriate drug than ethambutol, given its known ocular toxicity. Thus, the aim should have been to preserve the remaining healthy eye from an iatrogenic insult leading to irreversible loss of vision. Lastly, Grosse and colleagues mention that they excluded other causes of generalised lymphadenopathy, including toxoplasmosis, brucellosis, yersiniosis, and syphilis by serological tests. Such elaborate and costly serological investigations might not be possible and economically viable in a developing country like India, which bears 28·4% of the entire world’s burden of tuberculosis, and where every second an individual older than 20 years is infected with M tuberculosis.5 A simple biopsy of an easily accessible cervical lymph node would have been more appropriate. Abraham Kuruvilla Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695 011, India (e-mail: [email protected]) 1 2 3 4 5 Grosse V, Bange FC, Tischendorf J, Schmidt RE, Manns MP. A mass in the eye. Lancet 2002; 360: 922. Haas DW, Des Prez RM. Mycobacterium tuberculosis. In: Mandell GL, Bennett JE, Dolan R, eds. Principles and practices of infectious diseases, 4th edn. New York: Churchill Livingston, 1995: 2213–43. Garg SP, Venkatesh P. Ocular tuberculosis. In: Sharma SK, Mohan A, eds. Tuberculosis. New Delhi: Jaypee Brothers, 2001: 294–303. Vanscoy RE, Willowske CJ. Antituberculous agents. Mayo Clinic Proc 1992; 67: 179–87. Sharma SK. Introduction. In: Sharma SK, Mohan A, eds. Tuberculosis. New Delhi: Jaypee Brothers, 2001: 1–4. Histopathological results showed an eyeball full of necrotic tissue extending to the iris and ciliary body. Kuruvilla also argues that ethambutol is associated with optic neuritis and therefore should be used with caution in a patient who has lost already one eye. We were aware of this possible ocular toxicity, but thought it to be a problem only with higher doses.1 However, we acknowledge that there have been reports of serious visual impairment on conventional doses, with permanent blindness in some cases, and painfully slow recovery in others.2 Our treatment was guided by the current recommendation that, unless the rate of resistance to isoniazid is less than 4%, the initial antituberculosis treatment regimen should consist of isoniazid, rifampicin, pyrazinamide, and ethambutol or streptomycin.3 Optic neuritis due to ethambutol usually resolves after the drug is stopped.4 In this case, the patient was monitored closely for the development of symptoms and signs related to ocular toxicity. He developed no optic neuritis. We agree that, in a country like India, with relatively low income levels and high incidence of tuberculosis (184 cases per 100 000 people),5 serological investigations to exclude other causes of generalised lymphadenopathy might not be economically sound. In Germany, however, the incidence of tuberculosis is low (11 per 100 000). Therefore, while the diagnosis of tuberculosis was pending, other possible causes for generalised lymphadenopathy were excluded, which included serological tests for syphilis, toxoplasmosis, and brucellosis. *V Grosse, F C Bange, J Tischendorf, R E Schmidt, M P Manns Divisions of *Clinical Immunology (VG, RES), and Gastroenterology and Hepatology (JT, MPM), Department of Medicine, and Department of Microbiology (FCB), Hannover Medical School, 30625 Hannover, Germany (e-mail: [email protected]) 1 Authors’ reply 2 Sir—Abraham Kuruvilla is right that avoidance of ocular biopsy or enucleation is preferable if possible. Early diagnosis and treatment is essential for saving the sight of patients with ocular manifestations of tuberculosis. Yet in this case, the patient presented when infection was already far advanced and the eye could not be saved. Enucleation was done because of acute panophthalmitis and complete destruction of the overlying retina, and not exclusively for diagnostic reasons. 3 4 5 American Thoracic Society. Treatment of tuberculosis and tuberculosis infection in adults and children. Am J Respir Crit Care Med 1994; 149: 1359–74. Russo PA, Chaglasian MA. Toxic optic neuropathy associated with ethambutol: implications for current therapy. J Am Optom Assoc 1994; 65: 332–38. Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med 2001; 345: 189–200. Friedberg DN, Lorenzo-Latkany M. Ocular complications of tuberculosis. In: Rom WN, Garay SM, eds. Tuberculosis. Boston: Little, Brown and Company, 1996: 557–66. World Health Organization. Global tuberculosis control: surveillance, planning, financing. WHO Report 2002. Geneva: WHO, 2002. http://www.who.int/gtb/ publications/globrep02/index.html (accessed Jan 8, 2003). THE LANCET • Vol 361 • January 18, 2003 • www.thelancet.com Avoidance of bioflavonoid supplements during pregnancy Sir—On July 28, 2002, the Italian Health Ministry published a statement in the Gazzetta Ufficiale, ordering that all dietary supplements containing bioflavonoids should be labelled: “Not to be taken during pregnancy”. This precautionary decision was taken because of the possibility of an increased risk of severe diseases during the first year of life due to prenatal exposure to bioflavonoids. The scientific basis for this association was provided by reports that suggested a relation between dietary flavonoids and infant leukaemia.1,2 However, the discussion sections of these reports highlighted a large number of questions (epidemiological, molecular, and medical) that should be addressed and that make the relation between bioflavonoids and infant leukaemia very weak. Moreover, there is evidence that dietary bioflavonoids afford protection from cancer owing to their antioxidant properties.3–5 Supplements containing bioflavonoids and marketed in Italy provide a median of 50–60 mg/day (range 2–500) bioflavonoids. The average daily quantity of bioflavonoids in a Mediterranean diet is more than 2000 mg. Thus, although the supplements are probably not necessary, their average bioflavonoid content corresponds to 3–5% of the dietary intake in Italian pregnant women. Although the evidence provided by the above cited reports suggests that precautions could be taken, there are no scientific grounds for such a decision, nor for unduly alarming the public. In fact, the decision to label the supplements is now having a striking effect, and women who were taking supplements or who took them in pregnancy are becoming anxious about the possible effects of these tablets on their children. Furthermore, supplements contain other ingredients, such as folic acid, proteins, and minerals, which could be beneficial for pregnant women. To add to the confusion, no adequate information has been issued to physicians and health operators to allow risk-benefit analysis and risk communication. No other countries, to our knowledge, have forbidden these compounds in pregnancy. We believe that decisions concerning public health should not be taken without a proper strategy for risk assessment and risk communication, 261 For personal use. Only reproduce with permission from The Lancet Publishing Group.
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