- Email: [email protected]
ARTIFICIAL KIDNEY AND ARTIFICIAL LIVER
1451 in which
graphy
iopanoic acid (’ Telepaque ’) for oral cholecystoingested, there is no evidence of associated
was
drug therapy. In all cases for which I have sufficient information, the history fits the stress syndrome. I believe those patients who have inherited this disease risk in situations other than anaathesia, because it is made worse by emotional excitement and it must be recognised in order to advise them about medical care. are at
Department of Anesthesiology, University of Nebraska Medical Center, 42nd and Dewey Avenue, Omaha, Nebraska 68105, U.S.A.
‘
Radnor House,
Hay
on
Wye,
JAMES MATHERS.
Hereford HR3 5DQ.
ARTIFICIAL KIDNEY AND ARTIFICIAL DANIEL W. WINGARD.
INADEQUATE MOTHERS SiR,—Ifind it somewhat surprising that a letter from an institute of family psychiatry (Nov. 30, p. 1322) should advocate separation of the child from its inadequate mother. For one thing, it presupposes an inexhaustible supply of long-term foster parents, a condition which perhaps prevails in the Ipswich area, but certainly does not in this residential outer London borough. Baby-battering, like parasuicide, with which it is in many ways comparable, has no one single cause, and the study our controls, the more we realise that there few mothers indeed who are not potential babybatterers : there are rather high-risk and low-risk groups. But unhappy women have not been slow to learn that to admit to baby-battering or a fear of battering is to ensure immediate and continuing attention to their distress. All too often these young mothers have themselves been disadvantaged by parental loss or rejection from an early age and seem to choose as consorts men who, equally, are indifferent or uninvolved. The " remoteness from, and unresponsiveness to, the infant even from its birth " commented on by Dr Eickhoff (Nov. 9, p. 1152) is often determined by pre-existing depression, puerperal breakdown, or illness in the child which prevents normal bonding. In one case, for example, a harness fitted for correction of congenital dislocation of the hip made it impossible for the mother to nurse or breast-feed her baby. The aim is not, to quote Ms Osborn (Nov. 30, p. 1322), " to alter a woman’s personality overnight ": indeed, in a day-hospital setting, it can take months of skilled nursing supervision to bring about any appreciable improvement in mother/child relationship. But this gives time to treat any puerperal illness, and, working in close liaison with the health visitor and social services, to involve other members of the family; meanwhile these inexperienced mothers and their children get the mothering they need, while contact with staff and less disturbed mothers provides a useful model of mothering behaviour. To keep staff anxiety at tolerable levels, we have to limit our number to six such mothers at a time, but, despite the slow gains, we feel this method preferable to the inevitable succession of short-term placements in care which merely serve to perpetuate the cycle of deprivation.
more we
are
Day Hospital, 77 Woodcote Road,
Wallington,
JOY WEST.
Surrey.
Sm,—Few would dissent from the proposition that when baby is battered it means that something is wrong with a parent, usually mother, even if mother’s disability is only given the imprecise label of inadequacy ". So what are the ethical and practical grounds on which Mrs Osborn (Nov. 30, p. 1322) recommends separation of the child from the mother-but only offers " love and care to the child ? Separation should surely be prescribed, if at all, a
"
"
1. Gelles, R. J.
only after the mother and child together have been thoroughly assessed, as inpatients if necessary, and a more precise diagnosis made of mother’s long-term incapacity. ’ During the assessment process, at least, one hopes that substitute love and care would be provided for them both.
Am. J. Orthopsych. 1973, 43/4,
611.
LIVER
SiR,—Iam writing to comment on your editorial on artificial liver (Oct. 26, p. 992) and also on Dr Oreopoulos’s letter (Sept. 28, p. 779) about your editorial on tomorrow’s artificial kidney (Aug. 24, p. 446). The charcoal artificial kidney to which Dr Oreopoulos referred is not the same as the microcapsule artificial kidney referred to in the editorial. The original charcoal artificial kidney consisted in perfusion of blood directly over charcoal granules,]. whereas the microcapsule artificial kidney depends on the principle of artificial cells using semipermeable microcapsules, studied in our laboratory since 1956.2-4 In the latter case, ultrathin biocompatible semipermeable membranes are made to envelop or coat various types of biologically active material, including enzymes, ion-exchange resin, and activated The enveloping biocompatible membranes charcoal. prevent the enclosed materials from having any adverse effects on the body, but at the same time allow permeant toxins or metabolites to enter the microcapsules to be acted on by the enclosed materials. Furthermore, because of the ultrathin membrane (300 A) and the high surface area (300 ml.) semipermeable microcapsules have a potential transport rate which is about 100 times that of the standard haemodialysers.2-4 We use charcoal as one of the microencapsulated materials because activated charcoal granules are effective in adsorbing many toxic materials, but when used for direct blood perfusion give off embolising particles and remove platelets. Microencapsulation of active charcoal granules by coating with biocompatible membranes eliminates the problems of embolism and platelet removal and at the same time makes use of the adsorbing properties of charcoal, thus allowing clinical use in patients with renal failure, drug overdose, and hepatic failure. In animal experiments, we have also studied the microcapsule artificial kidney constructed from microencapsulated enzymes, ionexchange resin, and other adsorbents for the removal of other toxins or waste metabolites.2-4 In all these cases, we made use of the artificial-cell approach to contain biologically active material. If Dr Oreopoulos refers to the chapter on the microcapsule artificial kidney in the book on Renal Dialysis,5 the book on Artificial Cells,4 or detailed papers from this laboratory, he will find full credit attributed to Dr Yatzidi’s group for their use of direct charcoal ha:moperfusion and at the same time an account of our reasons for using the principle of artificial cells in the form of semipermeable microcapsules to envelop or coat the charcoal to avoid the adverse effects of direct perfusion. As discussed in your editorial on an artificial liver, the microcapsule approach in the form of coated charcoal is also being assessed for the treatment of hepatic failure at McGill6 and more recently at King’s.’I A complete artificial liver 1. Yatzidis, H. Eur. Dial. Transplant. Ass. Proc. 1964, 1, 83. 2. Chang, T. M. S. Trans. Am. Soc. artif. intern. Organs, 1966, 12, 13. 3. Chang, T. M. S. Science, 1964, 146, 524. 4. Chang, T. M. S. Artificial Cells. Springfield, Illinois, 1972. 5. Renal Dialysis (edited by D. Whelpton). London, 1974. 6. Chang, T. M. S. Lancet, 1972, ii, 1371. 7. Gazzard, B. G., Weston, M. J., Murray-Lyon, I. M., Flax, H., Record, C. D., Portmann, B., Langley, P. G., Dunlop, E. H.,
Mellon, P. J., Ward, M. D., Williams, R. ibid. 1974, i, 1301.
1452 would require other systems like enzymes and other adsorbents. Since these cannot be used. directly for haemoperfusion, we are continuing our studies with the artificialcell approach of immobilising enzymes, ion-exchange resin, and other adsorbents which have already been demonstrated experimentally in animal studies in this labora-
tory. 2-4 Department of Physiology, McIntyre Medical Sciences Building, 3655 Drummond Street, Montreal, Quebec H3G 1Y6.
take issue with our conclusions on delayed recovery after minor head injury. Unfortunately their report 8 has not yet reached New Zealand, but presumably, in their words, it shows that " when using several neurological and psychological methods of investigation, we were unable to find any indications of traumatic cerebral lesions responsible for late post-concussional symptoms in general, but we found signs that the emotional shock often provoked by the accident, as well as apprehension connected with the early post-traumatic symptoms, is of importance in the development of late post-concussional symptoms." The key to our difference is that we have indeed found such changes in intellectual function after minor head injury. With the rest of their conclusions we are in hearty agreement, with the stipulation that impairment of intellectual capacity is an intensely disruptive event and well capable of provoking the emotional shock which they describe. We agree that it is in order to draw attention to the informality of our statement that there was " a strong clinical impression " that symptoms were associated with a low PASAT score and improved as the score returned to normal. We used this phrase because we found it difficult to quantitate the syndrome of poor concentration, fatigue, irritability, and headache in any way that did not merely dress clinical observation in a respectable garment of number, and as the findings are easy to confirm, contented ourselves with saying what we saw. Their surprise that so simple a test as the PASAT should be so sensitive an index we can easily understand. It has surprised, and delighted, us. One of us (D. G.) has described 9 the experimental details and theoretical considerations. If Dr Lidvall and Dr Linderoth remain unconvinced, we urge them to add the test to their battery, and we feel sure that they will gain insight into one of the sources of the emotional shock which they predicate.
New Zealand.
DOROTHY GRONWALL PHILIP WRIGHTSON.
LOCALISATION OF PHÆOCHROMOCYTOMA SIR,-We wish to report a symptom that occurred during the management of a patient with a phaeochromocytoma, and which may be useful in the localisation of the tumour. A 56-year-old man with hypertension, after giving a history of paroxysmal sweating and palpitations, was found to have high levels of vanillylmandelic acid and normethadrenaline in his urine. An intravenous pyelogram and renal arteriogram suggested the presence of a tumour in the left suprarenal area, but they were not entirely conclusive. It was decided to do a laparotomy, and
preoperative
management
was
x-blocker.) However, it was noticed that if the phentolamine was injected quickly, the patient complained of pain in the left subcostal region, localised to an area of approximately 2 in. diameter in the midclavicular line. This persisted for several minutes and was associated with flushing and a feeling of heat. However, these symptoms did not occur if the phentolamine was given slowly over 10-15 minutes. A laparotomy was subsequently performed and the tumour was found in the left suprarenal gland, and successfully removed.
We do
T. M. S. CHANG.
RECOVERY AFTER MINOR HEAD INJURY SIR,-Dr Lidvall and Dr Linderoth (Nov. 9, p. 1150)
Department of Neurosurgery, Auckland Hospital, Auckland,
amine and oral propranolol. (Phentolamine was used after discussion with the anxsthetist, who requested the use of a short-acting
started with intravenous
phentol-
not
know of any other reports of this reaction to
phentolamine, although diffuse pain in the chest and abdomen sometimes occurs during provocation tests with histamine, but these are not now normally performed, Therefore, we suggest that this symptom may be of use in the localisation of a phxochromocytoma when other investigations, such as arteriography and differential catecholamine estimation, King Edward VII Hospital, Windsor, Berkshire SL4 3DP.
inconclusive.
J. P. SIMMONDS J. LISTER R. J. LUCK.
BLOOD FRACTIONS FOR HÆMOPHILIA
SiR,—I read with great interest the many issues raised Dr Biggs (June 29, p. 1339). The problems are by no means unique to England-we face them in America, and
by all
over
the world.
availability of blood products for the treatment of haemophilia and the means to pay for them go hand in hand. The advent of reconstructive surgery and the growing worldwide application of home therapy (self-therapy) pose a great threat to our supplies of blood. Therapy deThe
mands international conservation of blood and Government support. Modern technology, often reached by Governmentsupported research, has produced methods of breaking down blood into its many components and fractionating plasma into factor vni and ix concentrates. However, the increasing concern of the World Health Organisation over the advisability and/or safety of long-term plasmaphereses (either voluntary or commercial) threatens the means of supply. Lack of information, poor blood-banking technology, and inadequately trained personnel in many parts of the world lead to inadequate treatment of haemophilia. They also waste one of our few recyclable natural resources - blood. If more and more countries do not produce large quantities of plasma or cryoprecipitate as substrate for haemophilia products, we will increase (1) efflux of plasma from countries permitting plasmapheresis and (2) cost. At present the United States is the major producer of factor VIII and ix concentrates. The demand for these products is growing both here and abroad. With inflation
alone, costs are rising at a frightening rate. Regulations affecting the quantity of plasma collected at any one time are becoming more restrictive. In addition third-party payment is inadequate to meet the costs of the hxmophilia patient and his family in many parts of the world. Some solutions to these problems are to: (1) improve blood-banking technology throughout the world; (2) begin international conservation of plasma and plasma products; (3) disseminate information on haemophilia treatment; (4) convince our Governments that these materials will lead to better care for haemophiliacs, so that
they
can
become
more
International Hemophilia
Lidvall, H. F., Linderoth, B., Norlin, B. Acta neurol. scand. 1974, 50, suppl. 56. 9. Gronwall, D. M. A., Sampson, H. The Psychological Effects of Concussion. Auckland, 1974. 8.
are
productive citizens.
Training
Center, Mount Sinai School of Medicine, City University of New York, New York 10029, U.S.A.
LOUIS M. ALEDORT.
graphy
iopanoic acid (’ Telepaque ’) for oral cholecystoingested, there is no evidence of associated
was
drug therapy. In all cases for which I have sufficient information, the history fits the stress syndrome. I believe those patients who have inherited this disease risk in situations other than anaathesia, because it is made worse by emotional excitement and it must be recognised in order to advise them about medical care. are at
Department of Anesthesiology, University of Nebraska Medical Center, 42nd and Dewey Avenue, Omaha, Nebraska 68105, U.S.A.
‘
Radnor House,
Hay
on
Wye,
JAMES MATHERS.
Hereford HR3 5DQ.
ARTIFICIAL KIDNEY AND ARTIFICIAL DANIEL W. WINGARD.
INADEQUATE MOTHERS SiR,—Ifind it somewhat surprising that a letter from an institute of family psychiatry (Nov. 30, p. 1322) should advocate separation of the child from its inadequate mother. For one thing, it presupposes an inexhaustible supply of long-term foster parents, a condition which perhaps prevails in the Ipswich area, but certainly does not in this residential outer London borough. Baby-battering, like parasuicide, with which it is in many ways comparable, has no one single cause, and the study our controls, the more we realise that there few mothers indeed who are not potential babybatterers : there are rather high-risk and low-risk groups. But unhappy women have not been slow to learn that to admit to baby-battering or a fear of battering is to ensure immediate and continuing attention to their distress. All too often these young mothers have themselves been disadvantaged by parental loss or rejection from an early age and seem to choose as consorts men who, equally, are indifferent or uninvolved. The " remoteness from, and unresponsiveness to, the infant even from its birth " commented on by Dr Eickhoff (Nov. 9, p. 1152) is often determined by pre-existing depression, puerperal breakdown, or illness in the child which prevents normal bonding. In one case, for example, a harness fitted for correction of congenital dislocation of the hip made it impossible for the mother to nurse or breast-feed her baby. The aim is not, to quote Ms Osborn (Nov. 30, p. 1322), " to alter a woman’s personality overnight ": indeed, in a day-hospital setting, it can take months of skilled nursing supervision to bring about any appreciable improvement in mother/child relationship. But this gives time to treat any puerperal illness, and, working in close liaison with the health visitor and social services, to involve other members of the family; meanwhile these inexperienced mothers and their children get the mothering they need, while contact with staff and less disturbed mothers provides a useful model of mothering behaviour. To keep staff anxiety at tolerable levels, we have to limit our number to six such mothers at a time, but, despite the slow gains, we feel this method preferable to the inevitable succession of short-term placements in care which merely serve to perpetuate the cycle of deprivation.
more we
are
Day Hospital, 77 Woodcote Road,
Wallington,
JOY WEST.
Surrey.
Sm,—Few would dissent from the proposition that when baby is battered it means that something is wrong with a parent, usually mother, even if mother’s disability is only given the imprecise label of inadequacy ". So what are the ethical and practical grounds on which Mrs Osborn (Nov. 30, p. 1322) recommends separation of the child from the mother-but only offers " love and care to the child ? Separation should surely be prescribed, if at all, a
"
"
1. Gelles, R. J.
only after the mother and child together have been thoroughly assessed, as inpatients if necessary, and a more precise diagnosis made of mother’s long-term incapacity. ’ During the assessment process, at least, one hopes that substitute love and care would be provided for them both.
Am. J. Orthopsych. 1973, 43/4,
611.
LIVER
SiR,—Iam writing to comment on your editorial on artificial liver (Oct. 26, p. 992) and also on Dr Oreopoulos’s letter (Sept. 28, p. 779) about your editorial on tomorrow’s artificial kidney (Aug. 24, p. 446). The charcoal artificial kidney to which Dr Oreopoulos referred is not the same as the microcapsule artificial kidney referred to in the editorial. The original charcoal artificial kidney consisted in perfusion of blood directly over charcoal granules,]. whereas the microcapsule artificial kidney depends on the principle of artificial cells using semipermeable microcapsules, studied in our laboratory since 1956.2-4 In the latter case, ultrathin biocompatible semipermeable membranes are made to envelop or coat various types of biologically active material, including enzymes, ion-exchange resin, and activated The enveloping biocompatible membranes charcoal. prevent the enclosed materials from having any adverse effects on the body, but at the same time allow permeant toxins or metabolites to enter the microcapsules to be acted on by the enclosed materials. Furthermore, because of the ultrathin membrane (300 A) and the high surface area (300 ml.) semipermeable microcapsules have a potential transport rate which is about 100 times that of the standard haemodialysers.2-4 We use charcoal as one of the microencapsulated materials because activated charcoal granules are effective in adsorbing many toxic materials, but when used for direct blood perfusion give off embolising particles and remove platelets. Microencapsulation of active charcoal granules by coating with biocompatible membranes eliminates the problems of embolism and platelet removal and at the same time makes use of the adsorbing properties of charcoal, thus allowing clinical use in patients with renal failure, drug overdose, and hepatic failure. In animal experiments, we have also studied the microcapsule artificial kidney constructed from microencapsulated enzymes, ionexchange resin, and other adsorbents for the removal of other toxins or waste metabolites.2-4 In all these cases, we made use of the artificial-cell approach to contain biologically active material. If Dr Oreopoulos refers to the chapter on the microcapsule artificial kidney in the book on Renal Dialysis,5 the book on Artificial Cells,4 or detailed papers from this laboratory, he will find full credit attributed to Dr Yatzidi’s group for their use of direct charcoal ha:moperfusion and at the same time an account of our reasons for using the principle of artificial cells in the form of semipermeable microcapsules to envelop or coat the charcoal to avoid the adverse effects of direct perfusion. As discussed in your editorial on an artificial liver, the microcapsule approach in the form of coated charcoal is also being assessed for the treatment of hepatic failure at McGill6 and more recently at King’s.’I A complete artificial liver 1. Yatzidis, H. Eur. Dial. Transplant. Ass. Proc. 1964, 1, 83. 2. Chang, T. M. S. Trans. Am. Soc. artif. intern. Organs, 1966, 12, 13. 3. Chang, T. M. S. Science, 1964, 146, 524. 4. Chang, T. M. S. Artificial Cells. Springfield, Illinois, 1972. 5. Renal Dialysis (edited by D. Whelpton). London, 1974. 6. Chang, T. M. S. Lancet, 1972, ii, 1371. 7. Gazzard, B. G., Weston, M. J., Murray-Lyon, I. M., Flax, H., Record, C. D., Portmann, B., Langley, P. G., Dunlop, E. H.,
Mellon, P. J., Ward, M. D., Williams, R. ibid. 1974, i, 1301.
1452 would require other systems like enzymes and other adsorbents. Since these cannot be used. directly for haemoperfusion, we are continuing our studies with the artificialcell approach of immobilising enzymes, ion-exchange resin, and other adsorbents which have already been demonstrated experimentally in animal studies in this labora-
tory. 2-4 Department of Physiology, McIntyre Medical Sciences Building, 3655 Drummond Street, Montreal, Quebec H3G 1Y6.
take issue with our conclusions on delayed recovery after minor head injury. Unfortunately their report 8 has not yet reached New Zealand, but presumably, in their words, it shows that " when using several neurological and psychological methods of investigation, we were unable to find any indications of traumatic cerebral lesions responsible for late post-concussional symptoms in general, but we found signs that the emotional shock often provoked by the accident, as well as apprehension connected with the early post-traumatic symptoms, is of importance in the development of late post-concussional symptoms." The key to our difference is that we have indeed found such changes in intellectual function after minor head injury. With the rest of their conclusions we are in hearty agreement, with the stipulation that impairment of intellectual capacity is an intensely disruptive event and well capable of provoking the emotional shock which they describe. We agree that it is in order to draw attention to the informality of our statement that there was " a strong clinical impression " that symptoms were associated with a low PASAT score and improved as the score returned to normal. We used this phrase because we found it difficult to quantitate the syndrome of poor concentration, fatigue, irritability, and headache in any way that did not merely dress clinical observation in a respectable garment of number, and as the findings are easy to confirm, contented ourselves with saying what we saw. Their surprise that so simple a test as the PASAT should be so sensitive an index we can easily understand. It has surprised, and delighted, us. One of us (D. G.) has described 9 the experimental details and theoretical considerations. If Dr Lidvall and Dr Linderoth remain unconvinced, we urge them to add the test to their battery, and we feel sure that they will gain insight into one of the sources of the emotional shock which they predicate.
New Zealand.
DOROTHY GRONWALL PHILIP WRIGHTSON.
LOCALISATION OF PHÆOCHROMOCYTOMA SIR,-We wish to report a symptom that occurred during the management of a patient with a phaeochromocytoma, and which may be useful in the localisation of the tumour. A 56-year-old man with hypertension, after giving a history of paroxysmal sweating and palpitations, was found to have high levels of vanillylmandelic acid and normethadrenaline in his urine. An intravenous pyelogram and renal arteriogram suggested the presence of a tumour in the left suprarenal area, but they were not entirely conclusive. It was decided to do a laparotomy, and
preoperative
management
was
x-blocker.) However, it was noticed that if the phentolamine was injected quickly, the patient complained of pain in the left subcostal region, localised to an area of approximately 2 in. diameter in the midclavicular line. This persisted for several minutes and was associated with flushing and a feeling of heat. However, these symptoms did not occur if the phentolamine was given slowly over 10-15 minutes. A laparotomy was subsequently performed and the tumour was found in the left suprarenal gland, and successfully removed.
We do
T. M. S. CHANG.
RECOVERY AFTER MINOR HEAD INJURY SIR,-Dr Lidvall and Dr Linderoth (Nov. 9, p. 1150)
Department of Neurosurgery, Auckland Hospital, Auckland,
amine and oral propranolol. (Phentolamine was used after discussion with the anxsthetist, who requested the use of a short-acting
started with intravenous
phentol-
not
know of any other reports of this reaction to
phentolamine, although diffuse pain in the chest and abdomen sometimes occurs during provocation tests with histamine, but these are not now normally performed, Therefore, we suggest that this symptom may be of use in the localisation of a phxochromocytoma when other investigations, such as arteriography and differential catecholamine estimation, King Edward VII Hospital, Windsor, Berkshire SL4 3DP.
inconclusive.
J. P. SIMMONDS J. LISTER R. J. LUCK.
BLOOD FRACTIONS FOR HÆMOPHILIA
SiR,—I read with great interest the many issues raised Dr Biggs (June 29, p. 1339). The problems are by no means unique to England-we face them in America, and
by all
over
the world.
availability of blood products for the treatment of haemophilia and the means to pay for them go hand in hand. The advent of reconstructive surgery and the growing worldwide application of home therapy (self-therapy) pose a great threat to our supplies of blood. Therapy deThe
mands international conservation of blood and Government support. Modern technology, often reached by Governmentsupported research, has produced methods of breaking down blood into its many components and fractionating plasma into factor vni and ix concentrates. However, the increasing concern of the World Health Organisation over the advisability and/or safety of long-term plasmaphereses (either voluntary or commercial) threatens the means of supply. Lack of information, poor blood-banking technology, and inadequately trained personnel in many parts of the world lead to inadequate treatment of haemophilia. They also waste one of our few recyclable natural resources - blood. If more and more countries do not produce large quantities of plasma or cryoprecipitate as substrate for haemophilia products, we will increase (1) efflux of plasma from countries permitting plasmapheresis and (2) cost. At present the United States is the major producer of factor VIII and ix concentrates. The demand for these products is growing both here and abroad. With inflation
alone, costs are rising at a frightening rate. Regulations affecting the quantity of plasma collected at any one time are becoming more restrictive. In addition third-party payment is inadequate to meet the costs of the hxmophilia patient and his family in many parts of the world. Some solutions to these problems are to: (1) improve blood-banking technology throughout the world; (2) begin international conservation of plasma and plasma products; (3) disseminate information on haemophilia treatment; (4) convince our Governments that these materials will lead to better care for haemophiliacs, so that
they
can
become
more
International Hemophilia
Lidvall, H. F., Linderoth, B., Norlin, B. Acta neurol. scand. 1974, 50, suppl. 56. 9. Gronwall, D. M. A., Sampson, H. The Psychological Effects of Concussion. Auckland, 1974. 8.
are
productive citizens.
Training
Center, Mount Sinai School of Medicine, City University of New York, New York 10029, U.S.A.
LOUIS M. ALEDORT.