914
Cardiovascular system design and barosaurus SiR,—The recent reconstruction ofbarosaurus on display at the American Museum of Natural History has renewed considerable interest in the biology of gigantic, extinct sauropods, whose postural behaviours are poorly known. New paleontological findings together with reinterpretations of posture and movement based on features of anatomy have increased the information base from which physiological understanding of dinosaurs might be advanced. Dr Choy and Dr Altman’s (Aug 29, p 534) ideas about the cardiovascular design necessary for providing blood flow to the head of barosaurus are highly speculative. The evolution of accessory hearts in vertebrates other than hagfish is possible but, in the case of barosaurus, very unlikely. Choy and Altman not only lack supportive evidence for their speculation but also present arguments that are flawed conceptually. The average height of a barosaurus with an erect neck was substantially less than the 15 m height of the museum skeletal display depicting forelimbs reared off the ground, and the length of the neck (hence blood column between heart and head) was closer to 8 m than to the 12 m they use in their calculations.’ Therefore, we calculate that an average systemic arterial blood pressure of about 740 mm Hg would have been needed at the heart of barosaurus, in contrast with their figure of 880 mm Hg (systolic pressure). We assumed reptilian density of blood and an average arterial blood pressure of 100 mm Hg at the head necessary to perfuse the cephalic vasculature, as in the giraffe.2,3 Choy and Altman’s suggestion that "check valves" were needed in the neck of barosaurus is not compelling since such valves are absent from the neck arteries of giraffes in which retrograde flow can be demonstrated (Hicks J, Hargens AR, Badeer H, unpublished observations). The imaginary accessory hearts would not need double sets of valves because the column is interrupted at sufficiently short intervals to allow the lower heart to fill the heart above it, so that one set of valves would suffice for each heart. More importantly, their scheme of heart and pumping arrangements would probably create non-continuous blood flow at the brain, which seems a poor arrangement for active and possibly endothermic sauropods. Certainly, the presence of six accessory hearts within the long and heavy neck of barosaurus would pose risks of damage or interruption of blood flow during activities such as combat, mating, and falling to the ground from syncope. Choy and Altman’s proposals are further embellished by an imaginary neural control scheme with linked antagonistic actions between hearts and sequence. But how would these hearts function when stimulated by circulating catecholamines? It is naive to conclude that living giraffes lack either a carotid sinus or barostatic reflex on the basis of early reports of heart rate stability in sedated animals.’ Other workers have shown inverse relations between heart rate and arterial blood pressure in conscious upright giraffes, which tend to confirm the presence of neural reflex regulation of heart rate.S Nor do Choy and Altman address the issue of how six pulsating hearts might be accommodated within the sauropod neck, which, by analogy with giraffes, probably consisted of very firm tissue and external covering. The statement that barosaurus was predisoposed to atherosclerosis and thereby subject to coronary artery disease might tantalise the medical reader, but such a conclusion is ill-founded. In some species of birds, which are more closely related to reptiles than are mammals, there is little correlation between hypertension and atherosclerosis.’ Moreover, low rather than high blood pressure may be associated with higher mortality in chickens, which is in contrast with data for man.’ Finally, Choy and Altman conclude that because soft tissues are not preserved along with fossils, we can only "speculate on, and not reconstruct" the cardiovascular features of large dinosaurs such as barosaurus. We remind readers that living giraffes have adapted a high gravitational pressure gradients in their cardiovascular system3 without the risky and unlikely anatomical features proposed by Choy and Altman. A more tenble proposition than that of Choy and Altman is that barosaurus was amphibious and supported its neck partly or occasionally in water.’ Perhaps sauropods had a bulbous enlargement of the root of the aorta as is seen in many species of marine mammals.8 The Windkessel function of such an "aortic
bulb" theoretically diminishes cardiac work while assisting the maintenance of blood pressure and flow against high levels of resistance. Department of Pharmacology and Cell Biophysics, College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267, USA
RONALD W. MILLARD
Department of Zoology, University of Florida, Gainesville, Florida
HARVEY B. LILLYWHITE
Life Science Division, NASA-Ames Research Center. Moffett Field, California
ALAN R. HARGENS
1. Lilleywhite HB. Sauropods and gravity. Nat History 1991; 100: 33. 2. Van Citters RL, Kemper WS, Franklin DL Blood flow and pressure m the giraffe carotid artery. Comp Biochem Physiol 1968; 24: 1035-42. 3. Hargens AR, Millard RW, Pettersson K, Johansen K. Gravitational haemodynamics and oedema prevention in the giraffe. Nature 1987; 329: 59-60 4. Goetz RH, Warren JV, Gauer OH, et al. Circulation of the giraffe. Circ Res 1960; 8:
1049-58.
RW, Hargens AR, Johansen K, et al. Baroreflex modulates heart rate in the giraffe. Fed Proc 1986; 45: 758
5. Millard
6. Krista LM, Mora EC, McDaniel GR. A comparison between aortic lumen surfaces of hypertensive and hypotensive turkeys. Poultry Sci 1979; 58: 738-44. 7 Sturkie PD, Ringer RK, Weiss HS. Relationship of blood pressure to mortality m chickens. Proc Soc Exp Biol Med 1956; 92: 301-03.
Diving and asphyxia. a comparative study of animals and man. Cambridge: Cambridge University Press, 1983: 186.
8 Elsner R, Gooden B
SIR,-Dr Choy and Dr Altman propose an unusual cardiovascular system for barosaurus. The reptilian vascular system of barosaurus would certainly differ much from the mammalian system of the giraffe, though the details of this are highly specialised.’ A similar arrangement of arteries is seen in the closely related okapi, despite its short neck. In neither of the two giraffes that I dissected were there valves at the openings of tributaries of the jugular vein, though these were very small, but specialised seried valves prevented reflux into tributaries running from below into large veins.2 Identical valves were, however, present in the neck of a Bactrian camel. Unless pressure was very low to start with, fresh preparations of these valves withstood 200 mm Hg. The giraffe must vary somewhat in its anatomy. Thus the specimen used for the classic description by R. Owen (Trans Zool Soc Lond 1841; 2: 217) had no gallbladder. If barosaurus did faint regularly the bones of its neck must have locked together. Can this be confirmed from skeletons? If a standing giraffe loses consciousness the weight of the cervical vertebrae produces a spectacular cervical dislocation. In a British Broadcasting Corporation television broadcast, in which I took part some years ago, keepers from Bristol Zoo demonstrated a scaffolding to support a giraffe when it was anaesthetised-a remarkable achievement with so timid an animal. The Old House,
Vowchurch, Hereford HR2 0RB, UK
R. E. REWELL
1. Lawrence WE, Rewell RE. The cerebral blood
supply in the Giraffidae. Proc Zool Soc Lond 1948; 118: 202-12. 2 Amoroso EC, Edholm OG, Rewell RE. Venous vavles in the giraffe, okapi, camel and ostrich Proc Zool Soc Lond 1947; 117: 435-40.
MRC and research
funding
SiR,—Malcolm Dean (Sept 26, p 779) seeks to put the Medical Research Council (MRC) "in the dock" over the way it funds research. He asks for a response. He makes three serious criticisms of MRC policy: that the career structure of full-time researchers has declined; that centrally directed research designed to achieve "predetermined and relatively short-term objectives" has been expanded; and that an "uncharismatic" leadership has "failed to squeeze sufficient funds out of ministers or inspire and enthuse researchers". No facts are adduced to support these wide-ranging allegations. First, the MRC employs the same number of full-time scientific staff as it did ten years ago. What "decline" is Dean referring to? We
915
do have real concerns about attracting bright young scientists into research and are trying to improve career structures and opportunities, but that is not evidence of decline. Second, less than 6% of our funds are applied in directed programmes. We have two such programmes, one on AIDS and one funding the Human Genome Project. Both are in response to urgent priorities, and the money for both came from additional government funding. Neither has drained funds from our traditional activities. Third, the MRC has secured an increase in funding of 20% over a five-year period and, indeed, Dean refers to this. The fruits of our investment continue to set international benchmarks for research achievement. Last year, the MRC supported research that resulted in the discovery of the hyperlipidaemia gene and the sex-reversed mouse; the development of an artificial immune system to make human antibodies without immunisation; the construction of the silicon neuron; the linking of diabetes to low birthweight; and clinical trials showing that stroke deaths and disability can be halved by surgery, and that folic acid supplements can prevent the birth of babies with neural-tube defects. Dean also alleges that the MRC had decided to reduce total funding for MRC units to move to a more centralised control of research. This is not so. Our aim has been over five years to recycle about a fifth of total unit resources into other areas. However, these other areas include new scientific programmes in existing units, starting up new units, and increased funds for the best programmes. Much of Dean’s article focuses on the experience of one witness, Dr David Pegg, and his account of the MRC’s decision to discontinue funding for his group. Dean says that "the quality of the [group’s] research was not in doubt"; the group had become "victim of an MRC agenda"; that agenda was to reduce the total funding of MRC units to "move to a more centralised control of research"; and the agenda was applied by a subcommittee of "two external assessors and three internal staff". The subcommittee in fact consisted of five external assessorsthere were no internal staff members-acting in an advisory capacity to the MRC’s Cell Board; there was no policy of diverting funds to directed programmes; and, lastly, the quality of research was in doubt. This last was the real difficulty. The Cell Board agreed that the merit of the work reported and proposed fell short of the competitive standard for support which was very stringent. In particular, the board considered that the group had become isolated from recent advances in cell and tissue biology and pathology, and the goal of clinically useful procedures still seemed not to be "around the corner". In this respect the position was largely unchanged from 1984, when the group’s work had last been reviewed. Hence the decision to withdraw funding. Medical Research Council, 20 Park Crescent, London W1 N 4AL, UK
Keep the details
D. A. REES, Secretary
in The Lancet
SIR,-For reasons beyond those you gave, one must deprecate your banishment from your pages of details of important papers on online electronic data sevices (Aug 29, p 519). First, this increases the already large information gulf between those in advantaged situations and those in poor institutions or countries who are often without ready or even any access to such electronic services. Second, this adds additional burdens to the critical reader of The Lancet who must now go to a new source to interpret and analyse a published result. Third, this diminishes The Lancet’s archival value to future medical historians. Moreover, one is also disturbed by your comments implying that fine details of interest "only" to meta-analysis are best omitted from the editions read by the general reader-only that detail really enables one to evaluate a research report. Any general reader interested in the details necessary to interpret a published report should expect, reasonably, to find them published with the results. Otherwise, the journal might just as well publish an abstract only. One can sympathise with need to conserve space, but there is a much simpler alternative. Publish the fine detail you disparage in the same small print in which you publish references, which are, after all, another type of fine detail of interest to only some readers of
any particular article. The material then is immediately available to all readers, and for those with visual handicap, a magnifying glass is far cheaper and, for some, far closer than a computer terminal and online access to electronic data sources. School of Public Health, University of California, Berkeley, CA 94720, USA
ERNEST B. HOOK
Difficulty with MEDLINE searches for randomised controlled trials SIR,-A prerequisite for conducting systematic reviews of randomised controlled trials (RCTs) of health care is identification of a high proportion of the relevant studies, to keep to a minimum both imprecision and bias in assessing the effects of treatment. We are therefore collaborating to establish a register of RCTs of mental health care. Although we recognise that MEDLINE searches may only identify a proportion of the relevant studies, we have begun with a search of MEDLINE on SilverPlatter. In doing so, we found inconsistencies and would draw them to the attention of others. Our search strategy used eleven terms, both free text (for example, "random") and medical subject headings (MeSH) (for example, "randomised controlled trials") to identify RCTs. These were connected by "or", and then combined by "and" with two further terms ("human" in MeSH and "mental disorders"), forming our baseline search. This baseline search was then compared systematically with an identical search, except that one of the original eleven terms was omitted. By this process we wished to investigate the contribution made by each of the eleven terms to the efficiency of the search. Initially the search behaved consistently and produced up to 800 citations. At various stages in the process, however, the search strategy began to produce inconsistent results without warning, even on the same computer and at the same sitting. It generated fewer citations than would have been expected from the differences between the baseline search and its various modifications. Thinking our approach might have been flawed, we repeated the search, at the same sitting, and the results became progressively more bizarre. We have now repeated the process several times, in several sessions, and on more than one computer. At all times we made sure that the memory on the several computers we tested was well within the SilverPlatter MEDLINE specification. We have found the same apparently random deterioration in the ability of Silver Platter MEDLINE to cope with an extended but logical search sequence. We reported our difficulty to SilverPlatter in London. First they sent us a new CD-ROM for the year we had been searching; they then provided an updated version of the software (31). Unfortunately, the same faults continued to occur. SilverPlatter then tested our search strategy on their own computer and also encountered this difficulty. This was their response: "SilverPlatter is grateful to the University for bringing this problem to our attention. This difficulty came to light as a result of the searches that the unit was running, which made considerable demands on a limited amount of memory. The unit’s computer meets our basic requirements and can therefore be seen as adequate for the job. We were able to run the search correctly by use of a larger amount of expanded memory, and have been able to isolate the difficulty as the way in which memory is handled by the computer. Of course, this bug should not have occurred, and we regret this; our programmers have isolated the problem and we are rectifying it at the moment. Commonly throughout the computer industry the increasing sophistication of retrieval software naturally leads to a greater use of a larger amount of memory. SilverPlatter prides itself on being able to offer a very large range of features using a minimum amount of memory, but inevitably there will occasionally be a conflict between the demands of the user and the capacity of the machine being used, and the difficulty identified by the University of Oxford is one example of this." We feel that people undertaking MEDLINE searches with the SilverPlatter system should be aware that the system’s ability to produce consistent output is questionable. Until these difficulties have been resolved, we recommend that searches should be
Cardiovascular system design and barosaurus SiR,—The recent reconstruction ofbarosaurus on display at the American Museum of Natural History has renewed considerable interest in the biology of gigantic, extinct sauropods, whose postural behaviours are poorly known. New paleontological findings together with reinterpretations of posture and movement based on features of anatomy have increased the information base from which physiological understanding of dinosaurs might be advanced. Dr Choy and Dr Altman’s (Aug 29, p 534) ideas about the cardiovascular design necessary for providing blood flow to the head of barosaurus are highly speculative. The evolution of accessory hearts in vertebrates other than hagfish is possible but, in the case of barosaurus, very unlikely. Choy and Altman not only lack supportive evidence for their speculation but also present arguments that are flawed conceptually. The average height of a barosaurus with an erect neck was substantially less than the 15 m height of the museum skeletal display depicting forelimbs reared off the ground, and the length of the neck (hence blood column between heart and head) was closer to 8 m than to the 12 m they use in their calculations.’ Therefore, we calculate that an average systemic arterial blood pressure of about 740 mm Hg would have been needed at the heart of barosaurus, in contrast with their figure of 880 mm Hg (systolic pressure). We assumed reptilian density of blood and an average arterial blood pressure of 100 mm Hg at the head necessary to perfuse the cephalic vasculature, as in the giraffe.2,3 Choy and Altman’s suggestion that "check valves" were needed in the neck of barosaurus is not compelling since such valves are absent from the neck arteries of giraffes in which retrograde flow can be demonstrated (Hicks J, Hargens AR, Badeer H, unpublished observations). The imaginary accessory hearts would not need double sets of valves because the column is interrupted at sufficiently short intervals to allow the lower heart to fill the heart above it, so that one set of valves would suffice for each heart. More importantly, their scheme of heart and pumping arrangements would probably create non-continuous blood flow at the brain, which seems a poor arrangement for active and possibly endothermic sauropods. Certainly, the presence of six accessory hearts within the long and heavy neck of barosaurus would pose risks of damage or interruption of blood flow during activities such as combat, mating, and falling to the ground from syncope. Choy and Altman’s proposals are further embellished by an imaginary neural control scheme with linked antagonistic actions between hearts and sequence. But how would these hearts function when stimulated by circulating catecholamines? It is naive to conclude that living giraffes lack either a carotid sinus or barostatic reflex on the basis of early reports of heart rate stability in sedated animals.’ Other workers have shown inverse relations between heart rate and arterial blood pressure in conscious upright giraffes, which tend to confirm the presence of neural reflex regulation of heart rate.S Nor do Choy and Altman address the issue of how six pulsating hearts might be accommodated within the sauropod neck, which, by analogy with giraffes, probably consisted of very firm tissue and external covering. The statement that barosaurus was predisoposed to atherosclerosis and thereby subject to coronary artery disease might tantalise the medical reader, but such a conclusion is ill-founded. In some species of birds, which are more closely related to reptiles than are mammals, there is little correlation between hypertension and atherosclerosis.’ Moreover, low rather than high blood pressure may be associated with higher mortality in chickens, which is in contrast with data for man.’ Finally, Choy and Altman conclude that because soft tissues are not preserved along with fossils, we can only "speculate on, and not reconstruct" the cardiovascular features of large dinosaurs such as barosaurus. We remind readers that living giraffes have adapted a high gravitational pressure gradients in their cardiovascular system3 without the risky and unlikely anatomical features proposed by Choy and Altman. A more tenble proposition than that of Choy and Altman is that barosaurus was amphibious and supported its neck partly or occasionally in water.’ Perhaps sauropods had a bulbous enlargement of the root of the aorta as is seen in many species of marine mammals.8 The Windkessel function of such an "aortic
bulb" theoretically diminishes cardiac work while assisting the maintenance of blood pressure and flow against high levels of resistance. Department of Pharmacology and Cell Biophysics, College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267, USA
RONALD W. MILLARD
Department of Zoology, University of Florida, Gainesville, Florida
HARVEY B. LILLYWHITE
Life Science Division, NASA-Ames Research Center. Moffett Field, California
ALAN R. HARGENS
1. Lilleywhite HB. Sauropods and gravity. Nat History 1991; 100: 33. 2. Van Citters RL, Kemper WS, Franklin DL Blood flow and pressure m the giraffe carotid artery. Comp Biochem Physiol 1968; 24: 1035-42. 3. Hargens AR, Millard RW, Pettersson K, Johansen K. Gravitational haemodynamics and oedema prevention in the giraffe. Nature 1987; 329: 59-60 4. Goetz RH, Warren JV, Gauer OH, et al. Circulation of the giraffe. Circ Res 1960; 8:
1049-58.
RW, Hargens AR, Johansen K, et al. Baroreflex modulates heart rate in the giraffe. Fed Proc 1986; 45: 758
5. Millard
6. Krista LM, Mora EC, McDaniel GR. A comparison between aortic lumen surfaces of hypertensive and hypotensive turkeys. Poultry Sci 1979; 58: 738-44. 7 Sturkie PD, Ringer RK, Weiss HS. Relationship of blood pressure to mortality m chickens. Proc Soc Exp Biol Med 1956; 92: 301-03.
Diving and asphyxia. a comparative study of animals and man. Cambridge: Cambridge University Press, 1983: 186.
8 Elsner R, Gooden B
SIR,-Dr Choy and Dr Altman propose an unusual cardiovascular system for barosaurus. The reptilian vascular system of barosaurus would certainly differ much from the mammalian system of the giraffe, though the details of this are highly specialised.’ A similar arrangement of arteries is seen in the closely related okapi, despite its short neck. In neither of the two giraffes that I dissected were there valves at the openings of tributaries of the jugular vein, though these were very small, but specialised seried valves prevented reflux into tributaries running from below into large veins.2 Identical valves were, however, present in the neck of a Bactrian camel. Unless pressure was very low to start with, fresh preparations of these valves withstood 200 mm Hg. The giraffe must vary somewhat in its anatomy. Thus the specimen used for the classic description by R. Owen (Trans Zool Soc Lond 1841; 2: 217) had no gallbladder. If barosaurus did faint regularly the bones of its neck must have locked together. Can this be confirmed from skeletons? If a standing giraffe loses consciousness the weight of the cervical vertebrae produces a spectacular cervical dislocation. In a British Broadcasting Corporation television broadcast, in which I took part some years ago, keepers from Bristol Zoo demonstrated a scaffolding to support a giraffe when it was anaesthetised-a remarkable achievement with so timid an animal. The Old House,
Vowchurch, Hereford HR2 0RB, UK
R. E. REWELL
1. Lawrence WE, Rewell RE. The cerebral blood
supply in the Giraffidae. Proc Zool Soc Lond 1948; 118: 202-12. 2 Amoroso EC, Edholm OG, Rewell RE. Venous vavles in the giraffe, okapi, camel and ostrich Proc Zool Soc Lond 1947; 117: 435-40.
MRC and research
funding
SiR,—Malcolm Dean (Sept 26, p 779) seeks to put the Medical Research Council (MRC) "in the dock" over the way it funds research. He asks for a response. He makes three serious criticisms of MRC policy: that the career structure of full-time researchers has declined; that centrally directed research designed to achieve "predetermined and relatively short-term objectives" has been expanded; and that an "uncharismatic" leadership has "failed to squeeze sufficient funds out of ministers or inspire and enthuse researchers". No facts are adduced to support these wide-ranging allegations. First, the MRC employs the same number of full-time scientific staff as it did ten years ago. What "decline" is Dean referring to? We
915
do have real concerns about attracting bright young scientists into research and are trying to improve career structures and opportunities, but that is not evidence of decline. Second, less than 6% of our funds are applied in directed programmes. We have two such programmes, one on AIDS and one funding the Human Genome Project. Both are in response to urgent priorities, and the money for both came from additional government funding. Neither has drained funds from our traditional activities. Third, the MRC has secured an increase in funding of 20% over a five-year period and, indeed, Dean refers to this. The fruits of our investment continue to set international benchmarks for research achievement. Last year, the MRC supported research that resulted in the discovery of the hyperlipidaemia gene and the sex-reversed mouse; the development of an artificial immune system to make human antibodies without immunisation; the construction of the silicon neuron; the linking of diabetes to low birthweight; and clinical trials showing that stroke deaths and disability can be halved by surgery, and that folic acid supplements can prevent the birth of babies with neural-tube defects. Dean also alleges that the MRC had decided to reduce total funding for MRC units to move to a more centralised control of research. This is not so. Our aim has been over five years to recycle about a fifth of total unit resources into other areas. However, these other areas include new scientific programmes in existing units, starting up new units, and increased funds for the best programmes. Much of Dean’s article focuses on the experience of one witness, Dr David Pegg, and his account of the MRC’s decision to discontinue funding for his group. Dean says that "the quality of the [group’s] research was not in doubt"; the group had become "victim of an MRC agenda"; that agenda was to reduce the total funding of MRC units to "move to a more centralised control of research"; and the agenda was applied by a subcommittee of "two external assessors and three internal staff". The subcommittee in fact consisted of five external assessorsthere were no internal staff members-acting in an advisory capacity to the MRC’s Cell Board; there was no policy of diverting funds to directed programmes; and, lastly, the quality of research was in doubt. This last was the real difficulty. The Cell Board agreed that the merit of the work reported and proposed fell short of the competitive standard for support which was very stringent. In particular, the board considered that the group had become isolated from recent advances in cell and tissue biology and pathology, and the goal of clinically useful procedures still seemed not to be "around the corner". In this respect the position was largely unchanged from 1984, when the group’s work had last been reviewed. Hence the decision to withdraw funding. Medical Research Council, 20 Park Crescent, London W1 N 4AL, UK
Keep the details
D. A. REES, Secretary
in The Lancet
SIR,-For reasons beyond those you gave, one must deprecate your banishment from your pages of details of important papers on online electronic data sevices (Aug 29, p 519). First, this increases the already large information gulf between those in advantaged situations and those in poor institutions or countries who are often without ready or even any access to such electronic services. Second, this adds additional burdens to the critical reader of The Lancet who must now go to a new source to interpret and analyse a published result. Third, this diminishes The Lancet’s archival value to future medical historians. Moreover, one is also disturbed by your comments implying that fine details of interest "only" to meta-analysis are best omitted from the editions read by the general reader-only that detail really enables one to evaluate a research report. Any general reader interested in the details necessary to interpret a published report should expect, reasonably, to find them published with the results. Otherwise, the journal might just as well publish an abstract only. One can sympathise with need to conserve space, but there is a much simpler alternative. Publish the fine detail you disparage in the same small print in which you publish references, which are, after all, another type of fine detail of interest to only some readers of
any particular article. The material then is immediately available to all readers, and for those with visual handicap, a magnifying glass is far cheaper and, for some, far closer than a computer terminal and online access to electronic data sources. School of Public Health, University of California, Berkeley, CA 94720, USA
ERNEST B. HOOK
Difficulty with MEDLINE searches for randomised controlled trials SIR,-A prerequisite for conducting systematic reviews of randomised controlled trials (RCTs) of health care is identification of a high proportion of the relevant studies, to keep to a minimum both imprecision and bias in assessing the effects of treatment. We are therefore collaborating to establish a register of RCTs of mental health care. Although we recognise that MEDLINE searches may only identify a proportion of the relevant studies, we have begun with a search of MEDLINE on SilverPlatter. In doing so, we found inconsistencies and would draw them to the attention of others. Our search strategy used eleven terms, both free text (for example, "random") and medical subject headings (MeSH) (for example, "randomised controlled trials") to identify RCTs. These were connected by "or", and then combined by "and" with two further terms ("human" in MeSH and "mental disorders"), forming our baseline search. This baseline search was then compared systematically with an identical search, except that one of the original eleven terms was omitted. By this process we wished to investigate the contribution made by each of the eleven terms to the efficiency of the search. Initially the search behaved consistently and produced up to 800 citations. At various stages in the process, however, the search strategy began to produce inconsistent results without warning, even on the same computer and at the same sitting. It generated fewer citations than would have been expected from the differences between the baseline search and its various modifications. Thinking our approach might have been flawed, we repeated the search, at the same sitting, and the results became progressively more bizarre. We have now repeated the process several times, in several sessions, and on more than one computer. At all times we made sure that the memory on the several computers we tested was well within the SilverPlatter MEDLINE specification. We have found the same apparently random deterioration in the ability of Silver Platter MEDLINE to cope with an extended but logical search sequence. We reported our difficulty to SilverPlatter in London. First they sent us a new CD-ROM for the year we had been searching; they then provided an updated version of the software (31). Unfortunately, the same faults continued to occur. SilverPlatter then tested our search strategy on their own computer and also encountered this difficulty. This was their response: "SilverPlatter is grateful to the University for bringing this problem to our attention. This difficulty came to light as a result of the searches that the unit was running, which made considerable demands on a limited amount of memory. The unit’s computer meets our basic requirements and can therefore be seen as adequate for the job. We were able to run the search correctly by use of a larger amount of expanded memory, and have been able to isolate the difficulty as the way in which memory is handled by the computer. Of course, this bug should not have occurred, and we regret this; our programmers have isolated the problem and we are rectifying it at the moment. Commonly throughout the computer industry the increasing sophistication of retrieval software naturally leads to a greater use of a larger amount of memory. SilverPlatter prides itself on being able to offer a very large range of features using a minimum amount of memory, but inevitably there will occasionally be a conflict between the demands of the user and the capacity of the machine being used, and the difficulty identified by the University of Oxford is one example of this." We feel that people undertaking MEDLINE searches with the SilverPlatter system should be aware that the system’s ability to produce consistent output is questionable. Until these difficulties have been resolved, we recommend that searches should be
