- Email: [email protected]
How tainted is medicine?
CORRESPONDENCE
from Solvay, Pfizer, GlaxoSmithKline, Wyeth-Ayerst, Lichtwer, and the American Psychiatric Association, has been a scientific adviser to Allergan, Solvay, Pfizer, GlaxoSmithKline, Forrest Pharmaceuticals Inc, Ely Lilley, Ancile, Roche, Novartis, and Organon. Unbiased?
1
Editorial. Just how tainted has medicine become? Lancet 2002; 359: 1167.
DW is a part time independent consultant to Lichtwer Pharma.
Sir—Your anonymous editorialist refers to issues1 that have been aired openly and comprehensively in our own journal, the British Journal of Psychiatry. I suggest that readers look up the original correspondence for the full facts.
David Wheatley
Greg Wilkinson
69 Broughton Avenue, Richmond, Surrey TW10 7UL, UK
British Journal of Psychiatry, Royal College of Psychiatrists, London SW1X 8PG, UK
1 2
3
4
Editorial. Just how tainted has medicine become? Lancet 2002; 359: 1167. Larkin M. St John’s wort not effective for major depression, report US researchers. Lancet 2002; 359: 1317. Hypericum Depression Study Group. Effect of Hypericum perforatum (St John’s Wort) in major depressive disorder. JAMA 2002; 287: 1807–14. Linde K, Mulrow CD. St Johns Wort for depression (Cochrane review). In: The Cochrane Library, issue 2. Oxford: Update Software, 1999.
Sir—We notice that you illustrate your Editorial1 with a reference to the editor of the British Journal of Psychiatry. The ghost writing of academic articles has also been of concern for you, the British Medical Journal, the Journal of the American Medical Association, and the New England Journal of Medicine . Although ghost writing and editors’ conflicts of interests may be of concern, the primary issue seems to lie in the potential discrepancy between the reports editors publish or that academic investigators put their names to, and the raw data. If there is no discrepancy, it could even be said that an editor’s connections may facilitate the publication of important studies, and ghost writers may ensure a more rapid publication of better written articles. However, if discrepancies do exist, your policy of asking editors to divest themselves of all such commercial links upon assuming their duties is no real protection against reports that show only part of the data. Given that there are good grounds to think there are serious discrepancies between publications in your journal, the Journal of the American Medical Association, and the British Medical Journal, as well as the British Journal of Psychiatry, and the datasets from which they derive, we call on you to advocate the only logical answer to the problem—a refusal to publish studies without the entire raw dataset being made available. *G E Berrios, D Healy Department of Psychiatry, University of Cambridge and Robinson College, Addenbrooke’s Hospital, Box 189, Cambridge CB2 2QQ, UK (e-mail: [email protected])
1776
as schizophrenia and encephalopathy without cirrhosis. J Krøll Department of Clinical Chemistry, Blekinge County Hospital, Karlskrona, Sweden; *Godthåbsvej 111,3, DK 2000 Frederiksberg, Denmark (e-mail: [email protected]) 1 2
1 2
Editorial. Just how tainted has medicine become? Lancet 2002; 359: 1167. Conflict of interest and the British Journal of Psychiatry. Br J Psychiatry 2002; 180: 82–83.
Shunts in unexplained psychotic reactions and encephalopathy Sir—Non-hepatocellular liver dysfunction, caused by the presence of a congenital or acquired portasystemic shunt could cause the following signs of liver dysfunction in schizophrenia: raised concentrations of biogenic amines and metabolites in blood and the CNS; low CNS concentrations of ␥ aminobutyric acid; impaired glucose tolerance; increased antibody response to bacterial and viral antigens; raised concentrations of P-cortisol; increased exhaled pentane; raised free radicals in the CNS; Increased permeability of the bloodcerebrospinal fluid barrier; and cerebral atrophy with ventricular enlargement.1 The findings of a slight increase in the concentration of unconjugated bilirubin,2 lowered glutamate neurotransmission,3 and raised serum S1004 are in agreement with the suggestion of a liver dysfunction in schizophrenia. The shunt rate of the abnormal portocaval shunts, reported in a large proportion of psychotic patients, was probably less than 60%,1 since higher shunt rates dispose to hepatic encephalopathy,5 with raised concentration of P-ammonia and signs of a gross inhibition of the CNS uncommon in schizophrenia.1 Reports on the demonstration of abnormal congenital or acquired portosystemic shunts have been becoming more frequent because of the increased use of advanced noninvasive ultrasonography and magnetic resonance angiographic procedures. Since surgical correction of the shunts can reverse the hepatic dysfunction as well as the associated mental disorder, these procedures deserve a wider application in the hunt for abnormal portasystemic collaterals in cases of unexplained mental disturbances such
3
4
5
Krøll J. Schizophrenia and liver dysfunction. Med Hypoth 2001; 56: 634–36. Miyaoka T, Seno H, Itoga M, Iijima M, Inagaki T, Horiguchi J. Schizophreniaassociated idiopathic unconjugated hyperbilirubinemia (Gilbert’s syndrome). Clin Psychiatry 2000; 61: 868–71. Bleich S, Bleich K, Wiltfang J, Maler JM, Kornhuber J. Glutamaterge Neurotransmission bei Schizophrenien. Fortschr Neurol Psychiatr 2001; 69 (suppl 2): S56–61. Rothermundt M, Missler U, Arolt V, et al. Increased S100 blood levels in unmedicated and treated schizophrenic patients are correlated with negative symptomatology. Mol Psychiatry 2001; 6: 445–49. Uchino T, Matsuda I, Endo F. The longterm prognosis of congenital portosystemic venous shunt. J Pediatr 1999; 135: 254–56.
Decrease of resistance to imatinib in leukaemia Sir—James Griffin’s Feb 9 Commentary1 about resistance to targeted therapy in leukaemia, in response to the report by Nikolas von Bubnoff and colleagues (Feb 9, p 487),2 puts forward an exceptionally important question about the effectiveness of imatinib (STI571, a BCR-ABL tyrosine kinase inhibitor) for chronic myeloid, Philadelphia-chromosomepositive, and acute lymphoblastic leukaemia. He improves our understanding of the necessity for new strategies for disease control and treatment, including combined application of different substances with different contact sites. Kano and colleagues3 have reported a synergistic in-vitro effect of imatinib with several agents against Philadelphia-chromosome-positive leukaemia, such as recombinant and natural alfa interferons, as well as additive effects with cytarabine, homoharringtonine, etoposide, doxorubicin, and vincristine. Their findings suggest that imatinib combined with other conventional treatment agents, except methotrexate, can be advantageous for Philadelphia-chromosome-positive leukaemias. Kano and colleagues recommend a combined administration of imatinib and alfa interferons or vincristine as highly effective against these leukaemias. However, given possible discrepancies between in-vitro studies and clinical trials, these findings provide only useful
THE LANCET • Vol 359 • May 18, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
from Solvay, Pfizer, GlaxoSmithKline, Wyeth-Ayerst, Lichtwer, and the American Psychiatric Association, has been a scientific adviser to Allergan, Solvay, Pfizer, GlaxoSmithKline, Forrest Pharmaceuticals Inc, Ely Lilley, Ancile, Roche, Novartis, and Organon. Unbiased?
1
Editorial. Just how tainted has medicine become? Lancet 2002; 359: 1167.
DW is a part time independent consultant to Lichtwer Pharma.
Sir—Your anonymous editorialist refers to issues1 that have been aired openly and comprehensively in our own journal, the British Journal of Psychiatry. I suggest that readers look up the original correspondence for the full facts.
David Wheatley
Greg Wilkinson
69 Broughton Avenue, Richmond, Surrey TW10 7UL, UK
British Journal of Psychiatry, Royal College of Psychiatrists, London SW1X 8PG, UK
1 2
3
4
Editorial. Just how tainted has medicine become? Lancet 2002; 359: 1167. Larkin M. St John’s wort not effective for major depression, report US researchers. Lancet 2002; 359: 1317. Hypericum Depression Study Group. Effect of Hypericum perforatum (St John’s Wort) in major depressive disorder. JAMA 2002; 287: 1807–14. Linde K, Mulrow CD. St Johns Wort for depression (Cochrane review). In: The Cochrane Library, issue 2. Oxford: Update Software, 1999.
Sir—We notice that you illustrate your Editorial1 with a reference to the editor of the British Journal of Psychiatry. The ghost writing of academic articles has also been of concern for you, the British Medical Journal, the Journal of the American Medical Association, and the New England Journal of Medicine . Although ghost writing and editors’ conflicts of interests may be of concern, the primary issue seems to lie in the potential discrepancy between the reports editors publish or that academic investigators put their names to, and the raw data. If there is no discrepancy, it could even be said that an editor’s connections may facilitate the publication of important studies, and ghost writers may ensure a more rapid publication of better written articles. However, if discrepancies do exist, your policy of asking editors to divest themselves of all such commercial links upon assuming their duties is no real protection against reports that show only part of the data. Given that there are good grounds to think there are serious discrepancies between publications in your journal, the Journal of the American Medical Association, and the British Medical Journal, as well as the British Journal of Psychiatry, and the datasets from which they derive, we call on you to advocate the only logical answer to the problem—a refusal to publish studies without the entire raw dataset being made available. *G E Berrios, D Healy Department of Psychiatry, University of Cambridge and Robinson College, Addenbrooke’s Hospital, Box 189, Cambridge CB2 2QQ, UK (e-mail: [email protected])
1776
as schizophrenia and encephalopathy without cirrhosis. J Krøll Department of Clinical Chemistry, Blekinge County Hospital, Karlskrona, Sweden; *Godthåbsvej 111,3, DK 2000 Frederiksberg, Denmark (e-mail: [email protected]) 1 2
1 2
Editorial. Just how tainted has medicine become? Lancet 2002; 359: 1167. Conflict of interest and the British Journal of Psychiatry. Br J Psychiatry 2002; 180: 82–83.
Shunts in unexplained psychotic reactions and encephalopathy Sir—Non-hepatocellular liver dysfunction, caused by the presence of a congenital or acquired portasystemic shunt could cause the following signs of liver dysfunction in schizophrenia: raised concentrations of biogenic amines and metabolites in blood and the CNS; low CNS concentrations of ␥ aminobutyric acid; impaired glucose tolerance; increased antibody response to bacterial and viral antigens; raised concentrations of P-cortisol; increased exhaled pentane; raised free radicals in the CNS; Increased permeability of the bloodcerebrospinal fluid barrier; and cerebral atrophy with ventricular enlargement.1 The findings of a slight increase in the concentration of unconjugated bilirubin,2 lowered glutamate neurotransmission,3 and raised serum S1004 are in agreement with the suggestion of a liver dysfunction in schizophrenia. The shunt rate of the abnormal portocaval shunts, reported in a large proportion of psychotic patients, was probably less than 60%,1 since higher shunt rates dispose to hepatic encephalopathy,5 with raised concentration of P-ammonia and signs of a gross inhibition of the CNS uncommon in schizophrenia.1 Reports on the demonstration of abnormal congenital or acquired portosystemic shunts have been becoming more frequent because of the increased use of advanced noninvasive ultrasonography and magnetic resonance angiographic procedures. Since surgical correction of the shunts can reverse the hepatic dysfunction as well as the associated mental disorder, these procedures deserve a wider application in the hunt for abnormal portasystemic collaterals in cases of unexplained mental disturbances such
3
4
5
Krøll J. Schizophrenia and liver dysfunction. Med Hypoth 2001; 56: 634–36. Miyaoka T, Seno H, Itoga M, Iijima M, Inagaki T, Horiguchi J. Schizophreniaassociated idiopathic unconjugated hyperbilirubinemia (Gilbert’s syndrome). Clin Psychiatry 2000; 61: 868–71. Bleich S, Bleich K, Wiltfang J, Maler JM, Kornhuber J. Glutamaterge Neurotransmission bei Schizophrenien. Fortschr Neurol Psychiatr 2001; 69 (suppl 2): S56–61. Rothermundt M, Missler U, Arolt V, et al. Increased S100 blood levels in unmedicated and treated schizophrenic patients are correlated with negative symptomatology. Mol Psychiatry 2001; 6: 445–49. Uchino T, Matsuda I, Endo F. The longterm prognosis of congenital portosystemic venous shunt. J Pediatr 1999; 135: 254–56.
Decrease of resistance to imatinib in leukaemia Sir—James Griffin’s Feb 9 Commentary1 about resistance to targeted therapy in leukaemia, in response to the report by Nikolas von Bubnoff and colleagues (Feb 9, p 487),2 puts forward an exceptionally important question about the effectiveness of imatinib (STI571, a BCR-ABL tyrosine kinase inhibitor) for chronic myeloid, Philadelphia-chromosomepositive, and acute lymphoblastic leukaemia. He improves our understanding of the necessity for new strategies for disease control and treatment, including combined application of different substances with different contact sites. Kano and colleagues3 have reported a synergistic in-vitro effect of imatinib with several agents against Philadelphia-chromosome-positive leukaemia, such as recombinant and natural alfa interferons, as well as additive effects with cytarabine, homoharringtonine, etoposide, doxorubicin, and vincristine. Their findings suggest that imatinib combined with other conventional treatment agents, except methotrexate, can be advantageous for Philadelphia-chromosome-positive leukaemias. Kano and colleagues recommend a combined administration of imatinib and alfa interferons or vincristine as highly effective against these leukaemias. However, given possible discrepancies between in-vitro studies and clinical trials, these findings provide only useful
THE LANCET • Vol 359 • May 18, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.