- Email: [email protected]
Perceiving the world and grasping it: is there a difference?
-
^,,;;:::"_;;;’,’«wP’?
,
cardiorespiratory disturbances in a routine setting. Undoubtedly it will provoke renewed and constructive discussion among clinicians about the rationale for antihistamine prophylaxis, especially in subgroups of patients such as those with malignant disease. Time will tell whether the researchers’ suggestion will be generally approved-that "rather than relying on allegedly ’safe’ drugs that may in fact be dangerous in certain combinations, we should consider the benefits of routine antihistamine prophylaxis". If Haemaccel had not been used as an alternative to Ringer volume loading in the current investigation, no statistically significant effects of antihistamine prophylaxis might have been detected and no life-threatening disturbances observed.
Jørgen B Dahl Department of Anaesthesiology, Bispebjerg University Hospital, Copenhagen, Denmark 1
2
Fisher MMcD, More DG. The epidemiology and clinical features of anaphylactic reactions in anaesthesia. Anaesth Intensive Care 1981; 9: 226-34. Lorenz W, Roher HD, Doenicke A, Ohmann CH. Histamine release in anaesthesia and surgery: a new method to evaluate its clinical significance with several types of causal relationship. Clin Anaesthesiol
1984; 2: 403-26. 3
4 5
Østergaard D, Engbaek J, Viby-Mogensen J. Adverse reactions and interactions of the neuromuscular blocking drugs. Med Toxicol Adverse Drug Exp 1989; 4: 351-68. Fisher MMcD, Brady PW. Adverse reactions to plasma volume expanders. Drug Safety 1990; 5: 86-93. Fisher MMcD. Direct histamine release in anaesthesia and surgery: unanswered questions. Theor Surg 1988; 3: 145-47.
300 (60 die) in the medium exposure group catches up with the 200 who left midway in the high exposure group. In the G-technique, the two groups are compared by initial allocation: 100 of 400 with high exposure have died (rate 025) compared with 90 of 400 at medium exposure (0-23). The traditional technique paradoxically showed "dosedependent protection" by high exposure, whereas the Gmethod revealed hazard. Employment status (a surrogate for the healthy-worker survivor effect) is acting as a confounder and as an intermediate variable because, midway, it is an independent risk factor for mortality, predicts subsequent exposure, and is itself affected by past exposure. The G-null method does not estimate the size of any causal association. The G-computation algorithm does, but is said to be unwieldy. G-estimation evaluates change in life expectancy caused by exposure. There are differences between Robins’ ideas and traditional analyses. The G-methods do not directly relate traditional exposure measures to risk, exposures at different times are not directly combined, persons on or off work are not directly compared, and, for G-estimation at least, change in life expectancy can be examined. Arrighi and Hertz-Picciotto say that G-estimation has yet to be used in occupational studies. G-methods left the starting block in the mid-1980s, and should be increasing in credibility and usage in epidemiology.
remaining
David McNamee The Lancet, London, UK 1
Arrighi HM, Hertz-Picciotto I. The evolving concept of the healthy worker survivor effect. Epidemiology 1994; 5: 189-96.
Working to survive The healthy-worker survivor effect, the healthy-hire effect, and the decline in health with time-since-hire are components of the healthy-worker effect. Those who remain in work tend to be healthier than those who leave, and successful job applicants tend to be healthier than those turned down or not well
enough to apply. In occupational exposures (eg, to chemicals, radiation, or dust), the healthy-worker survivor effect may artifactually weaken the impact of exposure. The healthy-worker survivor effect can be regarded as a type of selection bias since employees may change tasks or occupation or leave work because of their health status; it is a bias because such changes are nonrandom. In traditional analysis, out of 800 exposed at work, say 40 of 200, 120 of 500, and 30 of 100 have died by the end of study after high, medium, and low exposures, respectively.’ The cumulative death rates are 0-20, 2-24, and 0-30. Arrighi and Hertz-Picciotto’ describe how James Robins and colleagues deal with the healthy-worker survivor effect as both a confounder and an intermediate variable in so-called G-methods-the G stands for "generalised". In the G-null test, out of our 800, say half have high and half have medium exposure. 200 with high exposure leave work midway through study (60 have died by study end); of the remaining 200, 40 die by study end. 100 with medium exposure leave work midway, to form, in effect, the low exposure group of the traditional analysis; 30 eventually die. Cumulative exposure of the
930
Perceiving the world and grasping it: is there
a
difference?
Vision is often identified with visual experience. However, conscious sight is only one of the functions of vision, and much of the work done by the visual system is inaccessible to experiential perception. Thus, recent observations of the residual visual abilities of patients with neurological deficits suggest that even complex visually guided behaviour-eg, reaching out for and grasping an object-may depend on visual mechanisms independent from those underlying the visual perception of that
object. Milner and colleagues described an instructive case.’ Patient DF is a young woman who developed a profound visual form agnosia after carbon-monoxide-induced anoxia. Her "low-level" visual abilities are reasonably intact, yet she can no longer recognise everyday objects or the faces of her friends and relatives; nor can she identify even the simplest of geometric shapes. (If an object is placed in her hand, of course, she has no trouble identifying it by touch.) Rerharkably, however, DF shows strikingly accurate guidance of her hand and finger movements when she attempts to pick up the very objects she cannot identify.2 Thus, when she reaches out to grasp objects of different ^sizes, her hand opens wider in midflight for larger objects than it does for smaller ones, just as it would in people with normal vision. Similarly, she
her hand and wrist normally when she reaches out to grasp objects in different orientations, and she places her fmgers correctly on the boundaries of objects of different shapes. At the same time, she is totally unable to describe or distinguish between any of these objects when they are presented to her in simple discrimination tests. In other words, although DF’s visual system cannot deliver any perceptual information about the size, shape, and orientation of objects, the visuomotor systems in DF’s brain that control the programming and execution of visually guided actions remain sensitive to these same object features. Whilst the damage in DF’s brain is diffuse, the ventrolateral regions of her occipital lobe are particularly compromised whereas the primary visual cortex seems to be largely spared. There is evidence that patients with damage to other visual areas in the cerebral cortex-eg, the superior regions of the posterior parietal cortex-show a pattern of visual behaviour that is essentially the mirror image of that of DF. Such patients are often unable to use visual information to rotate their hand or scale the opening of their fmgers when reaching out to pick up an object, even though they have no difficulty describing the size or orientation of objects in that part of the visual field.3°4 rotates
These neurological dissociations between vision for perception and vision for action have prompted a reexamination of how the visual pathways in the human (and monkey) brain might be organised. One proposal’ is that the division of labour between perception and action is reflected in a neuroanatomical distinction between the two major sets of visual projections, or "streams" of visual processing, that were identified over ten years ago6 in the primate cerebral cortex: a ventral stream arises in the primary visual cortex but projects to the inferotemporal dorsal stream also arises from the primary visual cortex but projects instead to the posterior parietal cortex. According to this new scheme,s the visual pathways in the ventral stream have the major role in the perceptual identification of objects and their spatial and temporal relations, while those in the dorsal stream mediate the visual control of skilled actions directed at those objects. Thus, processing in the ventral stream would allow us to identify an object such as a ripe pear in a basket of fruit, but processing in the dorsal stream would provide the critical information about the location, size, and shape of the pear so that we can accurately reach out and grasp it. If it is indeed the case that visual perception and the visual control of skilled movements are largely independent, can we fmd evidence for dissociations between these two kinds of processing even in people with normal vision? There are several clear demonstrations of such phenomena. For example, it is well known that our perception of the position of a small dot is affected to a large degree by the position of the frame surrounding the dot: when the frame is moved unexpectedly to the left, we typically see the frame as stationary and the dot as moving to the right. Nevertheless, our visuomotor systems are seldom fooled, and when we are asked to point to the dot our pointing movements are not influenced by changes in the position of the frame and we usually continue to point in the correct direction.’ Such paradoxes show that what we think we "see" is not always what guides our actions, cortex, and
and therefore provide powerful evidence for the parallel operation, within everyday life, of two types of visual processing, each apparently designed to serve different purposes and each characterised by different properties. 8,9 The evidence from patients with neurological disorders suggests that these two types of processing may depend on separate but interactive visual pathways in the cerebral cortex.
M A Goodale Department of Psychology and Graduate Program in Neuroscience, University of Western Ontario, London, Ontario, Canada 1 2
3
4
5 6
7
8
9
Milner AD, Perrett DI, Johnston RS, et al. Perception and action in ’visual form agnosia’. Brain 1991; 114: 405-28. Goodale MA, Milner AD, Jakobson LS, Carey DP. A neurological dissociation between perceiving objects and grasping them. Nature 1991; 349: 154-56. Perenin M-T, Vighetto A. Optic ataxia: a specific disruption in visuomotor mechanisms. I. Different aspects of the deficit in reaching for objects. Brain 1988; 111: 643-74. Jakobson LS, Archibald YM, Carey DP, Goodale MA. A kinematic analysis of reaching and grasping movements in a patient recovering from optic ataxia. Neuropsychologia 1991; 29: 803-09. Goodale MA, Milner AD. Separate visual pathways for perception and action. Trends Neurosci 1992; 15: 20-25. Ungerleider LG, Mishkin M. Two cortical visual systems. In: Ingle DJ, Goodale MA, Mansfield RJW, eds. Analysis of visual behavior. Cambridge, Mass: MIT Press, 1982: 549-86. Bridgeman B, Kirch M, Sperling A. Segregation of cognitive and motor aspects of visual function using induced motion. Percept Psychophys 1981; 34: 149-54. Goodale MA. Modularity in visuomotor control: from input to output. In: Pylyshyn Z, ed. Computational processes in human vision: an interdisciplinary perspective. Norwood, New Jersey: Ablex, 1988: 262-85. Bridgeman B, van der Heijden AHC, Velichovsky BM. A theory of visual stability across saccadic eye movements. Behav Brain Sci (in
press).
a
Cyclins and
cancer:
wheels within wheels
Uespite epidemiologicai and experimental evidence that cancer requires the accumulation of several distinct molecular events, the notion of a single fundamental cause remains popular, no doubt because it carries with it the possibility of a single universal solution. If the effects of all oncogene and tumour suppressor gene mutations could be shown ultimately to converge at a common point in the biochemical pathways that regulate cell growth and differentiation, perhaps the opposing concepts of multiple contributing events but a single "cause of cancer" might be reconciled. An obvious candidate for such a universal target must be the process that controls cell division. Over the past decade this area, surprisingly neglected by molecular oncologists, has proved a difficult but rewarding challenge to cell biologists. Working initially with Xenopus eggs and with yeasts, they have identified common features of cell cycle regulation in all higher organisms. There are two main control points in the cycle, one at the Gl/S transition (when the decision is made to start DNA replication) and the other at entry to mitosis. The determinants of both are protein kinases whose enzymatic activity is regulated by co-factors-proteins termed cyclins because their concentrations rise and fall throughout the cell cycle. Cyclin-dependent kinases (Cdks) and cyclins themselves are each grouped into
931
^,,;;:::"_;;;’,’«wP’?
,
cardiorespiratory disturbances in a routine setting. Undoubtedly it will provoke renewed and constructive discussion among clinicians about the rationale for antihistamine prophylaxis, especially in subgroups of patients such as those with malignant disease. Time will tell whether the researchers’ suggestion will be generally approved-that "rather than relying on allegedly ’safe’ drugs that may in fact be dangerous in certain combinations, we should consider the benefits of routine antihistamine prophylaxis". If Haemaccel had not been used as an alternative to Ringer volume loading in the current investigation, no statistically significant effects of antihistamine prophylaxis might have been detected and no life-threatening disturbances observed.
Jørgen B Dahl Department of Anaesthesiology, Bispebjerg University Hospital, Copenhagen, Denmark 1
2
Fisher MMcD, More DG. The epidemiology and clinical features of anaphylactic reactions in anaesthesia. Anaesth Intensive Care 1981; 9: 226-34. Lorenz W, Roher HD, Doenicke A, Ohmann CH. Histamine release in anaesthesia and surgery: a new method to evaluate its clinical significance with several types of causal relationship. Clin Anaesthesiol
1984; 2: 403-26. 3
4 5
Østergaard D, Engbaek J, Viby-Mogensen J. Adverse reactions and interactions of the neuromuscular blocking drugs. Med Toxicol Adverse Drug Exp 1989; 4: 351-68. Fisher MMcD, Brady PW. Adverse reactions to plasma volume expanders. Drug Safety 1990; 5: 86-93. Fisher MMcD. Direct histamine release in anaesthesia and surgery: unanswered questions. Theor Surg 1988; 3: 145-47.
300 (60 die) in the medium exposure group catches up with the 200 who left midway in the high exposure group. In the G-technique, the two groups are compared by initial allocation: 100 of 400 with high exposure have died (rate 025) compared with 90 of 400 at medium exposure (0-23). The traditional technique paradoxically showed "dosedependent protection" by high exposure, whereas the Gmethod revealed hazard. Employment status (a surrogate for the healthy-worker survivor effect) is acting as a confounder and as an intermediate variable because, midway, it is an independent risk factor for mortality, predicts subsequent exposure, and is itself affected by past exposure. The G-null method does not estimate the size of any causal association. The G-computation algorithm does, but is said to be unwieldy. G-estimation evaluates change in life expectancy caused by exposure. There are differences between Robins’ ideas and traditional analyses. The G-methods do not directly relate traditional exposure measures to risk, exposures at different times are not directly combined, persons on or off work are not directly compared, and, for G-estimation at least, change in life expectancy can be examined. Arrighi and Hertz-Picciotto say that G-estimation has yet to be used in occupational studies. G-methods left the starting block in the mid-1980s, and should be increasing in credibility and usage in epidemiology.
remaining
David McNamee The Lancet, London, UK 1
Arrighi HM, Hertz-Picciotto I. The evolving concept of the healthy worker survivor effect. Epidemiology 1994; 5: 189-96.
Working to survive The healthy-worker survivor effect, the healthy-hire effect, and the decline in health with time-since-hire are components of the healthy-worker effect. Those who remain in work tend to be healthier than those who leave, and successful job applicants tend to be healthier than those turned down or not well
enough to apply. In occupational exposures (eg, to chemicals, radiation, or dust), the healthy-worker survivor effect may artifactually weaken the impact of exposure. The healthy-worker survivor effect can be regarded as a type of selection bias since employees may change tasks or occupation or leave work because of their health status; it is a bias because such changes are nonrandom. In traditional analysis, out of 800 exposed at work, say 40 of 200, 120 of 500, and 30 of 100 have died by the end of study after high, medium, and low exposures, respectively.’ The cumulative death rates are 0-20, 2-24, and 0-30. Arrighi and Hertz-Picciotto’ describe how James Robins and colleagues deal with the healthy-worker survivor effect as both a confounder and an intermediate variable in so-called G-methods-the G stands for "generalised". In the G-null test, out of our 800, say half have high and half have medium exposure. 200 with high exposure leave work midway through study (60 have died by study end); of the remaining 200, 40 die by study end. 100 with medium exposure leave work midway, to form, in effect, the low exposure group of the traditional analysis; 30 eventually die. Cumulative exposure of the
930
Perceiving the world and grasping it: is there
a
difference?
Vision is often identified with visual experience. However, conscious sight is only one of the functions of vision, and much of the work done by the visual system is inaccessible to experiential perception. Thus, recent observations of the residual visual abilities of patients with neurological deficits suggest that even complex visually guided behaviour-eg, reaching out for and grasping an object-may depend on visual mechanisms independent from those underlying the visual perception of that
object. Milner and colleagues described an instructive case.’ Patient DF is a young woman who developed a profound visual form agnosia after carbon-monoxide-induced anoxia. Her "low-level" visual abilities are reasonably intact, yet she can no longer recognise everyday objects or the faces of her friends and relatives; nor can she identify even the simplest of geometric shapes. (If an object is placed in her hand, of course, she has no trouble identifying it by touch.) Rerharkably, however, DF shows strikingly accurate guidance of her hand and finger movements when she attempts to pick up the very objects she cannot identify.2 Thus, when she reaches out to grasp objects of different ^sizes, her hand opens wider in midflight for larger objects than it does for smaller ones, just as it would in people with normal vision. Similarly, she
her hand and wrist normally when she reaches out to grasp objects in different orientations, and she places her fmgers correctly on the boundaries of objects of different shapes. At the same time, she is totally unable to describe or distinguish between any of these objects when they are presented to her in simple discrimination tests. In other words, although DF’s visual system cannot deliver any perceptual information about the size, shape, and orientation of objects, the visuomotor systems in DF’s brain that control the programming and execution of visually guided actions remain sensitive to these same object features. Whilst the damage in DF’s brain is diffuse, the ventrolateral regions of her occipital lobe are particularly compromised whereas the primary visual cortex seems to be largely spared. There is evidence that patients with damage to other visual areas in the cerebral cortex-eg, the superior regions of the posterior parietal cortex-show a pattern of visual behaviour that is essentially the mirror image of that of DF. Such patients are often unable to use visual information to rotate their hand or scale the opening of their fmgers when reaching out to pick up an object, even though they have no difficulty describing the size or orientation of objects in that part of the visual field.3°4 rotates
These neurological dissociations between vision for perception and vision for action have prompted a reexamination of how the visual pathways in the human (and monkey) brain might be organised. One proposal’ is that the division of labour between perception and action is reflected in a neuroanatomical distinction between the two major sets of visual projections, or "streams" of visual processing, that were identified over ten years ago6 in the primate cerebral cortex: a ventral stream arises in the primary visual cortex but projects to the inferotemporal dorsal stream also arises from the primary visual cortex but projects instead to the posterior parietal cortex. According to this new scheme,s the visual pathways in the ventral stream have the major role in the perceptual identification of objects and their spatial and temporal relations, while those in the dorsal stream mediate the visual control of skilled actions directed at those objects. Thus, processing in the ventral stream would allow us to identify an object such as a ripe pear in a basket of fruit, but processing in the dorsal stream would provide the critical information about the location, size, and shape of the pear so that we can accurately reach out and grasp it. If it is indeed the case that visual perception and the visual control of skilled movements are largely independent, can we fmd evidence for dissociations between these two kinds of processing even in people with normal vision? There are several clear demonstrations of such phenomena. For example, it is well known that our perception of the position of a small dot is affected to a large degree by the position of the frame surrounding the dot: when the frame is moved unexpectedly to the left, we typically see the frame as stationary and the dot as moving to the right. Nevertheless, our visuomotor systems are seldom fooled, and when we are asked to point to the dot our pointing movements are not influenced by changes in the position of the frame and we usually continue to point in the correct direction.’ Such paradoxes show that what we think we "see" is not always what guides our actions, cortex, and
and therefore provide powerful evidence for the parallel operation, within everyday life, of two types of visual processing, each apparently designed to serve different purposes and each characterised by different properties. 8,9 The evidence from patients with neurological disorders suggests that these two types of processing may depend on separate but interactive visual pathways in the cerebral cortex.
M A Goodale Department of Psychology and Graduate Program in Neuroscience, University of Western Ontario, London, Ontario, Canada 1 2
3
4
5 6
7
8
9
Milner AD, Perrett DI, Johnston RS, et al. Perception and action in ’visual form agnosia’. Brain 1991; 114: 405-28. Goodale MA, Milner AD, Jakobson LS, Carey DP. A neurological dissociation between perceiving objects and grasping them. Nature 1991; 349: 154-56. Perenin M-T, Vighetto A. Optic ataxia: a specific disruption in visuomotor mechanisms. I. Different aspects of the deficit in reaching for objects. Brain 1988; 111: 643-74. Jakobson LS, Archibald YM, Carey DP, Goodale MA. A kinematic analysis of reaching and grasping movements in a patient recovering from optic ataxia. Neuropsychologia 1991; 29: 803-09. Goodale MA, Milner AD. Separate visual pathways for perception and action. Trends Neurosci 1992; 15: 20-25. Ungerleider LG, Mishkin M. Two cortical visual systems. In: Ingle DJ, Goodale MA, Mansfield RJW, eds. Analysis of visual behavior. Cambridge, Mass: MIT Press, 1982: 549-86. Bridgeman B, Kirch M, Sperling A. Segregation of cognitive and motor aspects of visual function using induced motion. Percept Psychophys 1981; 34: 149-54. Goodale MA. Modularity in visuomotor control: from input to output. In: Pylyshyn Z, ed. Computational processes in human vision: an interdisciplinary perspective. Norwood, New Jersey: Ablex, 1988: 262-85. Bridgeman B, van der Heijden AHC, Velichovsky BM. A theory of visual stability across saccadic eye movements. Behav Brain Sci (in
press).
a
Cyclins and
cancer:
wheels within wheels
Uespite epidemiologicai and experimental evidence that cancer requires the accumulation of several distinct molecular events, the notion of a single fundamental cause remains popular, no doubt because it carries with it the possibility of a single universal solution. If the effects of all oncogene and tumour suppressor gene mutations could be shown ultimately to converge at a common point in the biochemical pathways that regulate cell growth and differentiation, perhaps the opposing concepts of multiple contributing events but a single "cause of cancer" might be reconciled. An obvious candidate for such a universal target must be the process that controls cell division. Over the past decade this area, surprisingly neglected by molecular oncologists, has proved a difficult but rewarding challenge to cell biologists. Working initially with Xenopus eggs and with yeasts, they have identified common features of cell cycle regulation in all higher organisms. There are two main control points in the cycle, one at the Gl/S transition (when the decision is made to start DNA replication) and the other at entry to mitosis. The determinants of both are protein kinases whose enzymatic activity is regulated by co-factors-proteins termed cyclins because their concentrations rise and fall throughout the cell cycle. Cyclin-dependent kinases (Cdks) and cyclins themselves are each grouped into
931