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Viral illness and chronic fatigue (syndrome)
and H
pylori regression.
eradication will
no
longer
result in
tumour
have shown that a residual/relapsed low-grade component of gastric MALT-NHL may still be responsive to anti-bacterial therapy after remission of the high-grade constituent with conventional therapy. As also underscored by the six non-responding patients with high-grade MALTNHL in the Bayerdorffer-study, antibacterial treatment should not be chosen as primary therapy for high-grade MALT-NHL, but additional H pylori eradication may play a part in optimum treatment of an accompanying low-grade component. We
*Henk Boot,
Daphne de Jong, Peter van Heerde, Babs Taal
Departments of *Gastroenterology and Pathology, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands
Taal BG, Burgers JMV, van Heerde P, Hart AAM, Somers R. The clinical spectrum and treatment of primary non-Hodgkin’s lymphoma of the stomach. Ann Oncol 1993; 4: 839-46. 2 Kluin PM, van Krieken JHJM, Kleiverda K, Kluin-Nelemans, HC. Discordant morphologic characteristics of B-cell lymphomas in bone marrow and lymph node biopsies. Am J Clin Pathol 1990; 94: 59-66. 1
can only be understood when physical and boundaries are crossed, rather than adhered psychological to. We were therefore surprised by her subsequent criticism of The Lancet for publishing a prospective epidemiological study that looks at physical, social, and psychological risk factors. We know that many sufferers recall a viral infection around the start of their illness. However, our data suggest that such retrospective recall of distant events might be influenced by a number of biases and confounders, and does not exclude a chance association between a common exposure (viral infection) and a not uncommon outcome
such
SiR-Our report of the relation between viral infection and chronic fatigue syndrome (CFS) (May 27, p 1333) has excited predictable controversy (see correspondence July 1, p 47). We recruited 2376 subjects as viral cases or non-viral controls. 6 months later 84% were successfully followed up, not 48% as stated by Wookey. These questionnaires were completed by the patients, and not by the research nurses, as Wookey also suggests. At that stage, 36 (1-5%) had CFS, not six as MacIntyre claims. There was no association between viral exposure and CFS, with a trend for more CFS cases to be in the non-exposed group. As Shepherd points out, this weak association with non-exposure may be because the controls (a random sample of primary care consulters) included some whose presentation was related to psychological morbidity. Viral exposure did not predict subsequent chronic fatigue and CFS, but measures of psychological morbidity before presentation with a viral infection were associated with subsequent chronic fatigue and CFS. We agree with Shepherd that the sample did not include those who did not attend general practice, and who might have had more severe infection, but do not accept that because the study was based in general practice and not the community we were biasing the selection of viral cases towards those with health anxieties or psychological morbidity. 80% of adults visit their general practitioner every year.’ The use of population-based controls would thus have sampled largely from the same population, with similar rates of chronic fatigue and psychological morbidity.2 when the cohort was restricted to those Furthermore, without any baseline psychological morbidity there was still no postviral effect. We also agree with Shepherd that our results do not exclude a role for uncommon viral triggers, as we stated in our discussion. Our results suggest that common viral illnesses in primary care do not constitute an important risk factor for CFS, but that psychological morbidity does. Baschetti criticises us for dropping the measurements of lymphadenopathy, fever, and pharyngitis. However, these measures have been shown to be unreliable3 and do not serve to distinguish CFS from depression. They were removed from the criteria for CFS by the National Institutes of Health3 and Centers for Disease Control and Prevention.4 Like Wookey we have consistently argued that illnesses
CFS
(CFS). *Trudie Chalder, Simon David Wright
Wessely, Paul Wallace, Steven Hirsch,
*Academic Department of Psychological Medicine, King’s College School of Medicine and Dentistry, and the Institute of Psychiatry, 103 Denmark Hill, London SE5 8A2, UK; Department of Primary Care, Royal Free Hospital School of Medicine, London NW3; and Departments of Psychiatry and Medical Microbiology, Charing Cross and Westminster Medical School, London W6
1
2
Viral illness and chronic fatigue (syndrome)
as
McCormick A,
Fleming D, Charlton J. Morbidity statistics from general practice: fourth national study 1991-1992. (Series MB5 no 3 ed.) London: HM Stationery Office, 1995. Pawlikowska T, Chalder T, Hirsch S, Wallace P, Wright D, Wessely S. A population based study of fatigue and psychological distress. BMJ 1994; 308: 743-46.
3
4
Schluederberg A, Straus S, Peterson P, et al. Chronic fatigue syndrome research: definition and medical outcome assessment. Ann Intern Med 1992; 117: 325-31. Fukuda K, Straus S, Hickie I, Sharpe M, Dobbins J, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med 1994; 121: 953-59.
Coagulation disorders
in bushmaster
envenomation SIR-Lachesis muta muta or bushmaster, the largest new world pit viper, is distributed across the forested countryside of northern South America. Bushmaster venom is a complex mixture exhibiting proteolytic, neurotoxic, haemorrhagic, and clotting activities.’ Both a fibrinogen-clotting enzyme and a potent kininogenin have been identified.2,3 We report our experience with a patient bitten by such a snake, who developed haemorrhagic manifestations characterised by hypofibrinogenaemia without thrombocytopenia. His coagulation tests were remarkable in showing a prolonged prothrombin time (PT) despite a normal activated partial thromboplastin time (aPTT). A 28-year-old white man was bitten on his right hand by a juvenile bushmaster. Intense local pain and progressive inflammatory oedema rapidly ensued. On his arrival at hospital 45 min later, he had intense sweating, vomiting,
diarrhoea, conjunctival suffusion, sialorrhoea, divergent strabismus, dysarthria, dysphagia, bradycardia, hypotension, and respiratory distress. Due to lack of specific antivenin, he was given 100 mL intravenously of a polyvalent antivenin with neutralising activity against local Bothrops and Crotalus species. After 8 h, he was transferred to the intensive care unit. Physical examination on admission revealed moderate hard inflammatory oedema and several ecchymoses on his right arm. Incoagulable blood spilled from two fang marks. Abnormal laboratory data included 21-9X10"/L leucocytes with 94% neutrophils, serum alanine aminotransferase 88 U/L, serum fibrinogen 0-76 g/L, and a PT of 21.7 s (control 13-2) with a normal aPTT of 25-7 s (control 27-7). During the following 36 h he had continuous moderate bleeding from a phlebotomy site. Repeated coagulation tests showed an infinite clotting time with aPTT 22-6 s (control 28-5), PT 20.7 s (control 13-3),
watery
449
pylori regression.
eradication will
no
longer
result in
tumour
have shown that a residual/relapsed low-grade component of gastric MALT-NHL may still be responsive to anti-bacterial therapy after remission of the high-grade constituent with conventional therapy. As also underscored by the six non-responding patients with high-grade MALTNHL in the Bayerdorffer-study, antibacterial treatment should not be chosen as primary therapy for high-grade MALT-NHL, but additional H pylori eradication may play a part in optimum treatment of an accompanying low-grade component. We
*Henk Boot,
Daphne de Jong, Peter van Heerde, Babs Taal
Departments of *Gastroenterology and Pathology, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands
Taal BG, Burgers JMV, van Heerde P, Hart AAM, Somers R. The clinical spectrum and treatment of primary non-Hodgkin’s lymphoma of the stomach. Ann Oncol 1993; 4: 839-46. 2 Kluin PM, van Krieken JHJM, Kleiverda K, Kluin-Nelemans, HC. Discordant morphologic characteristics of B-cell lymphomas in bone marrow and lymph node biopsies. Am J Clin Pathol 1990; 94: 59-66. 1
can only be understood when physical and boundaries are crossed, rather than adhered psychological to. We were therefore surprised by her subsequent criticism of The Lancet for publishing a prospective epidemiological study that looks at physical, social, and psychological risk factors. We know that many sufferers recall a viral infection around the start of their illness. However, our data suggest that such retrospective recall of distant events might be influenced by a number of biases and confounders, and does not exclude a chance association between a common exposure (viral infection) and a not uncommon outcome
such
SiR-Our report of the relation between viral infection and chronic fatigue syndrome (CFS) (May 27, p 1333) has excited predictable controversy (see correspondence July 1, p 47). We recruited 2376 subjects as viral cases or non-viral controls. 6 months later 84% were successfully followed up, not 48% as stated by Wookey. These questionnaires were completed by the patients, and not by the research nurses, as Wookey also suggests. At that stage, 36 (1-5%) had CFS, not six as MacIntyre claims. There was no association between viral exposure and CFS, with a trend for more CFS cases to be in the non-exposed group. As Shepherd points out, this weak association with non-exposure may be because the controls (a random sample of primary care consulters) included some whose presentation was related to psychological morbidity. Viral exposure did not predict subsequent chronic fatigue and CFS, but measures of psychological morbidity before presentation with a viral infection were associated with subsequent chronic fatigue and CFS. We agree with Shepherd that the sample did not include those who did not attend general practice, and who might have had more severe infection, but do not accept that because the study was based in general practice and not the community we were biasing the selection of viral cases towards those with health anxieties or psychological morbidity. 80% of adults visit their general practitioner every year.’ The use of population-based controls would thus have sampled largely from the same population, with similar rates of chronic fatigue and psychological morbidity.2 when the cohort was restricted to those Furthermore, without any baseline psychological morbidity there was still no postviral effect. We also agree with Shepherd that our results do not exclude a role for uncommon viral triggers, as we stated in our discussion. Our results suggest that common viral illnesses in primary care do not constitute an important risk factor for CFS, but that psychological morbidity does. Baschetti criticises us for dropping the measurements of lymphadenopathy, fever, and pharyngitis. However, these measures have been shown to be unreliable3 and do not serve to distinguish CFS from depression. They were removed from the criteria for CFS by the National Institutes of Health3 and Centers for Disease Control and Prevention.4 Like Wookey we have consistently argued that illnesses
CFS
(CFS). *Trudie Chalder, Simon David Wright
Wessely, Paul Wallace, Steven Hirsch,
*Academic Department of Psychological Medicine, King’s College School of Medicine and Dentistry, and the Institute of Psychiatry, 103 Denmark Hill, London SE5 8A2, UK; Department of Primary Care, Royal Free Hospital School of Medicine, London NW3; and Departments of Psychiatry and Medical Microbiology, Charing Cross and Westminster Medical School, London W6
1
2
Viral illness and chronic fatigue (syndrome)
as
McCormick A,
Fleming D, Charlton J. Morbidity statistics from general practice: fourth national study 1991-1992. (Series MB5 no 3 ed.) London: HM Stationery Office, 1995. Pawlikowska T, Chalder T, Hirsch S, Wallace P, Wright D, Wessely S. A population based study of fatigue and psychological distress. BMJ 1994; 308: 743-46.
3
4
Schluederberg A, Straus S, Peterson P, et al. Chronic fatigue syndrome research: definition and medical outcome assessment. Ann Intern Med 1992; 117: 325-31. Fukuda K, Straus S, Hickie I, Sharpe M, Dobbins J, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med 1994; 121: 953-59.
Coagulation disorders
in bushmaster
envenomation SIR-Lachesis muta muta or bushmaster, the largest new world pit viper, is distributed across the forested countryside of northern South America. Bushmaster venom is a complex mixture exhibiting proteolytic, neurotoxic, haemorrhagic, and clotting activities.’ Both a fibrinogen-clotting enzyme and a potent kininogenin have been identified.2,3 We report our experience with a patient bitten by such a snake, who developed haemorrhagic manifestations characterised by hypofibrinogenaemia without thrombocytopenia. His coagulation tests were remarkable in showing a prolonged prothrombin time (PT) despite a normal activated partial thromboplastin time (aPTT). A 28-year-old white man was bitten on his right hand by a juvenile bushmaster. Intense local pain and progressive inflammatory oedema rapidly ensued. On his arrival at hospital 45 min later, he had intense sweating, vomiting,
diarrhoea, conjunctival suffusion, sialorrhoea, divergent strabismus, dysarthria, dysphagia, bradycardia, hypotension, and respiratory distress. Due to lack of specific antivenin, he was given 100 mL intravenously of a polyvalent antivenin with neutralising activity against local Bothrops and Crotalus species. After 8 h, he was transferred to the intensive care unit. Physical examination on admission revealed moderate hard inflammatory oedema and several ecchymoses on his right arm. Incoagulable blood spilled from two fang marks. Abnormal laboratory data included 21-9X10"/L leucocytes with 94% neutrophils, serum alanine aminotransferase 88 U/L, serum fibrinogen 0-76 g/L, and a PT of 21.7 s (control 13-2) with a normal aPTT of 25-7 s (control 27-7). During the following 36 h he had continuous moderate bleeding from a phlebotomy site. Repeated coagulation tests showed an infinite clotting time with aPTT 22-6 s (control 28-5), PT 20.7 s (control 13-3),
watery
449