356
Few writers mention this interval. According to Wolff,1 "between the visual disturbance and the headache phase there is a symptom-free phase when the patient feels relatively well". Selby2 noted one patient in whom the interval lasted 10-120 minutes and another less than 60 minutes. Paton3had unilateral facial pallor a few minutes before a visual aura that was accompanied by a dreamy state: "As the prodromal stage passes off in my case I have a feeling of unusual well-being, with some sweating down the side of the face which was pale: then in five to ten minutes the headache commences". "Headache follows aura with a free interval of less than 60 minutes" is mentioned in the International Headache Society Classification4 under diagnostic criteria for migraine with aura, but in the study cited most patients were not symptom-free and in five of twenty-five the interval was more than 1 hour. What could these symptoms signify? Feeling distant from the environment or other individuals is, to me, a new feature of migraine. Nevertheless the symptoms in this series suggest involvement of frontal lobes (fear, altered
relationship to environment), hypothalamus (tiredness), temporal lobe (dysphasia and dyslexia), and the brain as a whole (impaired coordination, inability to think or concentrate). If I am correct in concluding that the whole brain is involved (including the frontal lobes), and that this occurs immediately after excitation of the occipital cortex has provoked the aura, then the orderly progression postulated in the Leao "spreading" hypothesis5 becomes untenable.
In their subtlety the reported symptoms resemble premonitory symptoms.6 Are they of the same type? A prospective study is needed to answer this question, and to yield precise information on timing and sensations. Observations by relatives at the time can also be illuminating.6 Finally, there remains the difficulty of fitting such symptoms into the yet unknown migraine pathophysiology, although even from this pilot study the symptoms seem more in keeping with a neural than a vascular aetiology. Prodromes and the gap between the aura and headache onset may provide windows of insight into migraine pathogenesis unclouded by pain of the headache phase or the neurological symptoms during the aura.
REFERENCES 1. Wolff HG. Headache and other head pains. New York: Oxford University Press, 1963: 230. 2. Selby G. Migraine and its variants. Sydney: Addis, 1983: 38, 42. 3. Paton L. Discussion after a paper on migraine by Fisher JH. Proc R Soc Med 1919; 12: 53-54. 4. International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988; 8 (suppl 7): 21. 5. Lauritzen M, Olesen J. Regional cerebral blood flow during migraine attacks by xenon-133 inhalation and emission tomography. Brain 1984, 107: 457-61. 6. Blau JN. Clinical characteristics of premonitory symptoms in migraine. In: Amery WK, Wauquiere A, eds. The prelude to the migraine attack. London: Baillière Tindall, 1986: 39-43. 7. Blau JN. Migraine: theories of pathogenesis. Lancet 1992; 339: 1202-06.
VIEWPOINT The innocent research worker
"Don’t let anyone tell you that tropical research is a pushover". These words, uttered by my boss (an old tropical hand) are to reverberate through my mind during the ensuing months. I am on my way to the Medical Research Council laboratories in The Gambia, West Africa, my suitcase loaded with microscope slides, microhaematocrit tubes, BM stix, T. S. Eliot, and a large bottle of whisky. A blisteringly hot afternoon, two weeks later. I am standing in the paediatric ward of the Royal Victoria Hospital, Banjul. Sweat drips from my face, my ankles are swollen, and my mouth is parched. I long to relieve myself, but there has been no water at the hospital for the past three weeks, and it seems churlish to use the lavatory. Only one more hour to go until tea-time and the chance to slip next door to the Atlantic hotel. The ceiling fan ruffles my papers and disturbs the red dust on the floor. I pray that there won’t be another power cut today. From outside, in the bright sunshine, comes the sound of laughter and the clatter of metal bowls, as mothers gossip and children are fed. A woman appears, wearing off one shoulder a full-length cotton robe with a striking geometric pattern of blue and yellow. A length of the same cloth is wound around her head. A small foot protrudes at each side of her waist. Another potential recruit. Fatou, one of our four Gambian nurses, gets to work immediately. Consent is obtained, a
history taken. Now for the worst bit. How easy it sounds in a scientific paper, "... a 22-gauge teflon catheter was inserted into an antecubital vein". The reality is somewhat different. My victim is a biting, kicking, and screaming 2-year-old. Her veins, initially so obvious, have vanished. Her sweaty, sticky hand (why have they always just finished a meal of glutinous rice and fish?) squirms out of Fatou’s vice-like grip, whilst the tape sticks to me, the sheets, itself, to everything but the intended target. Noise is inversely related to size, and SC24 is very small. From across the room, SC18 looks at me suspiciously over a large ice-cream, while SA23 whenever I pass her bed. But it is getting late for the 18-hour sample from SA20. Deeply comatose yesterday, he is now sitting outside with his mother, while his younger sister lies comfortably asleep in her bed. After an unseemly amount of cajoling, massaging, and suction, I obtain what is now the 182-hour sample. A flush of pride is replaced by a surge of panic when I realise that one of the necessary tubes is downstairs in the fridge. Fatou disappears obligingly. How much blood into what tube? Spin? Freeze? Spin and freeze? Labelling is crucial. screams
ADDRESS: Department of Paediatrics, John Radcliffe Hospital, Oxford OX3 9DU, UK (Dr J. Crawley, MRCP)
357
SA20 at 18 hours or SA 18 at 20 hours? Remember to use the indelible pen, or prepare for black fingers, anonymous samples, and the wrath of the boss when the freezer is
opened. I hate thin films. The boss produces immaculate arcs of evenly spaced red blood cells. "The secret lies in a smooth sliding action". My own attempts produce smashed microscope slides or an opaque layer of cells and fibrinous clot. But persistence pays off and with a flourish I dip my
first successful attempt in the Field’s stain. The dried blood floats on the surface of the stain and my heart sinks when I realise that I have forgotten to fix the film with ethanol. Parasite counts are no better. I squint down the microscope, index finger rhythmically tapping the cell-counter. Splodge or parasite? Like housemaid’s knee or tennis elbow, malariologist’s finger is surely a well-recognised condition. Debbie emerges exhausted from the ward. "Schizont" makes a pretty effective swear-word, we decide. Time for a break. We amble next door to the Atlantic hotel in search of Vimto, that sugary blackcurrant drink consumed primarily in Manchester and West Africa. British tourists lie, like beached whales, around the swimming pool, gloriously unaware of the sickness and death next door. With the passing weeks they become plump and brown, while we remain thin and white.
It is dark when we return to our villa on the Medical Research Council compound. My turn to transfer some of our precious blood samples to the freezers in the main laboratory block. Last job before the preprandial gin and tonic. I place them carefully in the front basket of my bicycle. The road is bumpy and the bicycle jolts. There is a sickening scrunch, and my front tyre is punctured. So why do it? Tropical research sounds like a nightmare, you think. The reasons are manifold. The satisfaction of carrying out research that, in spite of the frustrations, is rigorous, demanding, but extremely enjoyable; the importance of trying to improve the treatment of falciparum malaria, a disease that kills two million children annually; the immense interest of working in a different culture and climate; the beauty of the African sky at night. Just like a thick film, as Debbie so lyrically puts it.
I would like to thank Dr Nicholas White, Dr Deborah Waller, Dr Francois Nosten, and Dr David Chapman for their help and friendship; Ms Fatou Sengore, Mr Simon Mendy, Mrs Antoinette Saar, and Mrs Hadi Nijie for skilled nursing assistance; Dr Brian Greenwood and colleagues at the Medical
Research Council for their support; the Wellcome Trust and the Wellcome Mahidol University-Oxford Tropical Medicine Research Programme; also the British Paediatric Association for awarding me a Heinz Travelling
Fellowship.
BOOKSHELF Research Fraud in the Behavioral and Biomedical Sciences Edited
Wiley.
by David J. Miller, Michael Hersen. New York: John 1992. Pp 251.$43.50/28.50. ISBN 0-471520683.
The public face of science in the US has recently been sullied by the spectacle of resentful scientists, including AIDS researcher Robert Gallo and Nobel laureate David
Baltimore, being interrogated by Representative John
Dingell, whose congressional subcommittee is investigating fraud. Indignation is widespread that scientific malefactors are going scot-free, while whistle-blowers are losing their jobs for telling the truth. The thirteen contributors to this volume approach scientific misconduct from various perspectives. The opening chapters present a theoretical overview, drawing on the ideas of social scientists, psychologists, and ethicists. Several case studies follow. One contributor believes that he unjustly stigmatised for collaborating with a fraudster. Other writers believe that co-authors should share responsibility for the integrity of their research. It will become clear to the reader that it is not easy for institutions to steer a middle course between a permissive Scylla, who erodes faith in science, and an inquisitorial Charybdis, who jeopardises scientific "collegiality". The point is repeatedly made that honest error is not fraud. To err is human, as the publishers have illustrated by sprinkling typos throughout the book. In Scientific Fraud or False Accusations? The Case for Cyril Burt, Arthur Jensen argues for the presumption of innocence. After reviewing the arguments for and against, Jensen finds the evidence "flimsy" that Sir Cyril Burt, "one of the dominant figures in the history of British psychology", was guilty of fraud. Burt was indeed eccentric and "politically incorrect", and was
his behaviour was sometimes questionable-though no more so than that of his accusers, whose zeal seemed motivated by the ideology underlying Lysenkoism. One anti-hereditarian adversary of Burt’s, who had never met him, rushed to his flat after his death to persuade his housekeeper that boxes of data should be burned. They were. In the final chapter of Research Fraud, the editors identify the "heart of the problem: the commercialism of academia and its attendant issues". A "market mentality to research" has led to anti-intellectualism and dishonesty. Research misconduct is especially serious when it involves "investigators who are paid by the large pharmaceutical conglomerates to evaluate their new drugs". Through an unholy alliance of dishonest government officials, pharmaceutical companies, and investigators, ineffective and dangerous drugs have been put on the market. When fraudulent research causes suffering and death for thousands of people, there is no room for leniency. The full penalties of the law, civil and criminal, should be applied to all the crooks-including the "scientists". 26 St Mark’s Place,
New York City, 10003 NY, USA
JOHN LAURITSEN
Health Care for Older Women
by Julie George and Shah Ebrahim. Oxford: Oxford University Press. 1992. Pp 267. 25. ISBN 0-192620681. Edited
Although there is a passage in Health Care for Older Women in which ageing is described as a trajectory towards death, there are several chapters that give life-enhancing discussions on exercise, the prevention of serious disease, and the promotion of sexuality in older women (lesbianism not excluded). There is poignant sadness too, reminiscent of
Few writers mention this interval. According to Wolff,1 "between the visual disturbance and the headache phase there is a symptom-free phase when the patient feels relatively well". Selby2 noted one patient in whom the interval lasted 10-120 minutes and another less than 60 minutes. Paton3had unilateral facial pallor a few minutes before a visual aura that was accompanied by a dreamy state: "As the prodromal stage passes off in my case I have a feeling of unusual well-being, with some sweating down the side of the face which was pale: then in five to ten minutes the headache commences". "Headache follows aura with a free interval of less than 60 minutes" is mentioned in the International Headache Society Classification4 under diagnostic criteria for migraine with aura, but in the study cited most patients were not symptom-free and in five of twenty-five the interval was more than 1 hour. What could these symptoms signify? Feeling distant from the environment or other individuals is, to me, a new feature of migraine. Nevertheless the symptoms in this series suggest involvement of frontal lobes (fear, altered
relationship to environment), hypothalamus (tiredness), temporal lobe (dysphasia and dyslexia), and the brain as a whole (impaired coordination, inability to think or concentrate). If I am correct in concluding that the whole brain is involved (including the frontal lobes), and that this occurs immediately after excitation of the occipital cortex has provoked the aura, then the orderly progression postulated in the Leao "spreading" hypothesis5 becomes untenable.
In their subtlety the reported symptoms resemble premonitory symptoms.6 Are they of the same type? A prospective study is needed to answer this question, and to yield precise information on timing and sensations. Observations by relatives at the time can also be illuminating.6 Finally, there remains the difficulty of fitting such symptoms into the yet unknown migraine pathophysiology, although even from this pilot study the symptoms seem more in keeping with a neural than a vascular aetiology. Prodromes and the gap between the aura and headache onset may provide windows of insight into migraine pathogenesis unclouded by pain of the headache phase or the neurological symptoms during the aura.
REFERENCES 1. Wolff HG. Headache and other head pains. New York: Oxford University Press, 1963: 230. 2. Selby G. Migraine and its variants. Sydney: Addis, 1983: 38, 42. 3. Paton L. Discussion after a paper on migraine by Fisher JH. Proc R Soc Med 1919; 12: 53-54. 4. International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988; 8 (suppl 7): 21. 5. Lauritzen M, Olesen J. Regional cerebral blood flow during migraine attacks by xenon-133 inhalation and emission tomography. Brain 1984, 107: 457-61. 6. Blau JN. Clinical characteristics of premonitory symptoms in migraine. In: Amery WK, Wauquiere A, eds. The prelude to the migraine attack. London: Baillière Tindall, 1986: 39-43. 7. Blau JN. Migraine: theories of pathogenesis. Lancet 1992; 339: 1202-06.
VIEWPOINT The innocent research worker
"Don’t let anyone tell you that tropical research is a pushover". These words, uttered by my boss (an old tropical hand) are to reverberate through my mind during the ensuing months. I am on my way to the Medical Research Council laboratories in The Gambia, West Africa, my suitcase loaded with microscope slides, microhaematocrit tubes, BM stix, T. S. Eliot, and a large bottle of whisky. A blisteringly hot afternoon, two weeks later. I am standing in the paediatric ward of the Royal Victoria Hospital, Banjul. Sweat drips from my face, my ankles are swollen, and my mouth is parched. I long to relieve myself, but there has been no water at the hospital for the past three weeks, and it seems churlish to use the lavatory. Only one more hour to go until tea-time and the chance to slip next door to the Atlantic hotel. The ceiling fan ruffles my papers and disturbs the red dust on the floor. I pray that there won’t be another power cut today. From outside, in the bright sunshine, comes the sound of laughter and the clatter of metal bowls, as mothers gossip and children are fed. A woman appears, wearing off one shoulder a full-length cotton robe with a striking geometric pattern of blue and yellow. A length of the same cloth is wound around her head. A small foot protrudes at each side of her waist. Another potential recruit. Fatou, one of our four Gambian nurses, gets to work immediately. Consent is obtained, a
history taken. Now for the worst bit. How easy it sounds in a scientific paper, "... a 22-gauge teflon catheter was inserted into an antecubital vein". The reality is somewhat different. My victim is a biting, kicking, and screaming 2-year-old. Her veins, initially so obvious, have vanished. Her sweaty, sticky hand (why have they always just finished a meal of glutinous rice and fish?) squirms out of Fatou’s vice-like grip, whilst the tape sticks to me, the sheets, itself, to everything but the intended target. Noise is inversely related to size, and SC24 is very small. From across the room, SC18 looks at me suspiciously over a large ice-cream, while SA23 whenever I pass her bed. But it is getting late for the 18-hour sample from SA20. Deeply comatose yesterday, he is now sitting outside with his mother, while his younger sister lies comfortably asleep in her bed. After an unseemly amount of cajoling, massaging, and suction, I obtain what is now the 182-hour sample. A flush of pride is replaced by a surge of panic when I realise that one of the necessary tubes is downstairs in the fridge. Fatou disappears obligingly. How much blood into what tube? Spin? Freeze? Spin and freeze? Labelling is crucial. screams
ADDRESS: Department of Paediatrics, John Radcliffe Hospital, Oxford OX3 9DU, UK (Dr J. Crawley, MRCP)
357
SA20 at 18 hours or SA 18 at 20 hours? Remember to use the indelible pen, or prepare for black fingers, anonymous samples, and the wrath of the boss when the freezer is
opened. I hate thin films. The boss produces immaculate arcs of evenly spaced red blood cells. "The secret lies in a smooth sliding action". My own attempts produce smashed microscope slides or an opaque layer of cells and fibrinous clot. But persistence pays off and with a flourish I dip my
first successful attempt in the Field’s stain. The dried blood floats on the surface of the stain and my heart sinks when I realise that I have forgotten to fix the film with ethanol. Parasite counts are no better. I squint down the microscope, index finger rhythmically tapping the cell-counter. Splodge or parasite? Like housemaid’s knee or tennis elbow, malariologist’s finger is surely a well-recognised condition. Debbie emerges exhausted from the ward. "Schizont" makes a pretty effective swear-word, we decide. Time for a break. We amble next door to the Atlantic hotel in search of Vimto, that sugary blackcurrant drink consumed primarily in Manchester and West Africa. British tourists lie, like beached whales, around the swimming pool, gloriously unaware of the sickness and death next door. With the passing weeks they become plump and brown, while we remain thin and white.
It is dark when we return to our villa on the Medical Research Council compound. My turn to transfer some of our precious blood samples to the freezers in the main laboratory block. Last job before the preprandial gin and tonic. I place them carefully in the front basket of my bicycle. The road is bumpy and the bicycle jolts. There is a sickening scrunch, and my front tyre is punctured. So why do it? Tropical research sounds like a nightmare, you think. The reasons are manifold. The satisfaction of carrying out research that, in spite of the frustrations, is rigorous, demanding, but extremely enjoyable; the importance of trying to improve the treatment of falciparum malaria, a disease that kills two million children annually; the immense interest of working in a different culture and climate; the beauty of the African sky at night. Just like a thick film, as Debbie so lyrically puts it.
I would like to thank Dr Nicholas White, Dr Deborah Waller, Dr Francois Nosten, and Dr David Chapman for their help and friendship; Ms Fatou Sengore, Mr Simon Mendy, Mrs Antoinette Saar, and Mrs Hadi Nijie for skilled nursing assistance; Dr Brian Greenwood and colleagues at the Medical
Research Council for their support; the Wellcome Trust and the Wellcome Mahidol University-Oxford Tropical Medicine Research Programme; also the British Paediatric Association for awarding me a Heinz Travelling
Fellowship.
BOOKSHELF Research Fraud in the Behavioral and Biomedical Sciences Edited
Wiley.
by David J. Miller, Michael Hersen. New York: John 1992. Pp 251.$43.50/28.50. ISBN 0-471520683.
The public face of science in the US has recently been sullied by the spectacle of resentful scientists, including AIDS researcher Robert Gallo and Nobel laureate David
Baltimore, being interrogated by Representative John
Dingell, whose congressional subcommittee is investigating fraud. Indignation is widespread that scientific malefactors are going scot-free, while whistle-blowers are losing their jobs for telling the truth. The thirteen contributors to this volume approach scientific misconduct from various perspectives. The opening chapters present a theoretical overview, drawing on the ideas of social scientists, psychologists, and ethicists. Several case studies follow. One contributor believes that he unjustly stigmatised for collaborating with a fraudster. Other writers believe that co-authors should share responsibility for the integrity of their research. It will become clear to the reader that it is not easy for institutions to steer a middle course between a permissive Scylla, who erodes faith in science, and an inquisitorial Charybdis, who jeopardises scientific "collegiality". The point is repeatedly made that honest error is not fraud. To err is human, as the publishers have illustrated by sprinkling typos throughout the book. In Scientific Fraud or False Accusations? The Case for Cyril Burt, Arthur Jensen argues for the presumption of innocence. After reviewing the arguments for and against, Jensen finds the evidence "flimsy" that Sir Cyril Burt, "one of the dominant figures in the history of British psychology", was guilty of fraud. Burt was indeed eccentric and "politically incorrect", and was
his behaviour was sometimes questionable-though no more so than that of his accusers, whose zeal seemed motivated by the ideology underlying Lysenkoism. One anti-hereditarian adversary of Burt’s, who had never met him, rushed to his flat after his death to persuade his housekeeper that boxes of data should be burned. They were. In the final chapter of Research Fraud, the editors identify the "heart of the problem: the commercialism of academia and its attendant issues". A "market mentality to research" has led to anti-intellectualism and dishonesty. Research misconduct is especially serious when it involves "investigators who are paid by the large pharmaceutical conglomerates to evaluate their new drugs". Through an unholy alliance of dishonest government officials, pharmaceutical companies, and investigators, ineffective and dangerous drugs have been put on the market. When fraudulent research causes suffering and death for thousands of people, there is no room for leniency. The full penalties of the law, civil and criminal, should be applied to all the crooks-including the "scientists". 26 St Mark’s Place,
New York City, 10003 NY, USA
JOHN LAURITSEN
Health Care for Older Women
by Julie George and Shah Ebrahim. Oxford: Oxford University Press. 1992. Pp 267. 25. ISBN 0-192620681. Edited
Although there is a passage in Health Care for Older Women in which ageing is described as a trajectory towards death, there are several chapters that give life-enhancing discussions on exercise, the prevention of serious disease, and the promotion of sexuality in older women (lesbianism not excluded). There is poignant sadness too, reminiscent of
