Journal of the Royal Society of Medicine Volume 85 June 1992
Letters to the Editor Preference is given to letters commenting on contributions recently published in the JRSMi They should not exceed
300 words and should be typed double-spaced.
Haemorheological treatment of ischaemia - facts or fancy? With reference to the editorial by Ernst (November 1991 JRSM, p 639) we suggest that this article has less emphasis on facts than fancy. There are a number of inaccuracies and omissions which we feel require correction. The author suggests that enhancing blood fluidity is recommended if vessel damage cannot be repaired, but fails to make the significant differentiation between micro and macrocirculatory pathophysiology. Current concepts of haemorheology are also studiously avoided. It is now accepted that events within the microcirculation determine outcome in ischaemia to a large extent. While it is true that red blood cells affect blood viscosity in the macrocirculation, this is not true of the microcirmulation. The main determinant of blood flow in capillaries (5-10 zm diameter) is the pressure gradient and the passage of larger cells, ie white blood cells. It has also been shown that low flow states increase interaction between leukocytes and vessel endothelium causing local perfusion defects, resulting in ischaemic damagel'2. Therefore, manipulation ofwhite cell function is thought to be of greater relevance than red cell deformability. The author is correct in stating that many drugs alter red cell deformability, but it is not surprising that mostly they have no clinical effect. One of the drugs showing good clinical results is pentoxifylline (Trental, Hoechst), whose principal method of action is not due to increased red cell deformability, but rather to actions on the white cell membrane3. Similarly, the vasodilatatory actions of these drugs contribute little when a system is maximally vasodilated. Other drugs, eg prostanoids, modify WBC behaviour and have been shown to have a beneficial clinical effect in critical ischaemia, but have not been mentioned by the author4. He then suggests that lowering plasma fibrinogen may be 'the most attractive haemorheological concept'. This statement is made without any supporting clinical evidence, and the theoretical basis is unsound as we have already stated that red cell aggregation is not the most important factor in microcirculatory flow. It is, therefore, unlikely to be 'the most valuable method of enhancing the flow properties of blood'. Finally, his statement that peripheral arterial occlusive disease (PAOD) can be treated successfully by rheological means is yet unproven in any useful clinical setting, though we would agree that research into pharmacological approaches offers potential benefits, which are now starting to be realized5'6. DAVID SHIELDS Department of Surgery SANJEEV SARINr The Middlesex Hospital, London W1N 8AA References 1 Nash GB, Thomas PRS, Dormandy JA. Abnormal flow properties of white blood cells in patients with severe ischaemia of the leg. BMJ 1988;296:1699-1701
2 Nees S, Schonharting M. Role of different blood cell types in blood rheology. In: Mandell GL, Novick WJ, eds. Pentoxifylline and leukocyte function. Hoechst-Roussel, 1987:105-14 3 Armstrong M, Needham D, Hatchell DL, Nunn RS. Effect of pentoxifylline on the flow of polymorphonuclear leukocytes through a model capillary. Angiology 1990; 41:253-62 4 de Gaetano G, Vertele V, Cerletti C. Mechanism of action and clinical use of prostanoids. In: Dormandy JA, Stock G, eds Critical leg ischaemia its pathophysiology and management. Berlin: Springer-Verlag, 1990:117-37 5 Colgan M-P, Dormandy JA, Jones PW, Schraibman IG, Shanik DG, Young RAL. Oxpentifylline treatment of venous ulcers of the leg. BMJ 1990;300:972-5 6 Lindgarde F, Jelnes R, Bjorkman H, et aL Conservative drug treatment in patients with moderately severe chronic occlusive peripheral arterial disease. Circulation
1989;80:1549-56 Do not resuscitate I was interested in McNeil's poem on the 'Do Not Resuscitate' order (August 1991 JRSM, p 512). This reminded me of a teaching hospital physician in Sydney who had recently retired. He had let it be known he did not want to be resuscitated, but when he had a cardiac arrest in another physician's surgery, cardiac massage was undertaken and he was revived. This physician went on for many years thereafter, with full mental and physical capacity and even became a computer enthusiast. He eventually did die but did not linger on into painful senility. There is a big difference from a resuscitation of 'ancient, suffering wrecks' and those who are, apart from their cardiac condition, in good physical and mental health. Methinks those who are fit but do not want to be resuscitated have made the ancient mistake of considering the heart to be the seat of the emotions. Of course, if the resuscitation is only partly successful, ones medical attendants should not be too tardy in turning off the machine! K B ORR 24 Belgrave Street Kogarah 2217, Australia
The COMA report: sugars and dental caries The views and interpretations expressed by Deery (October 1991 JRSM, p 635), in response to our letter (May 1991 JRSM, p 320), call for comment, since they are contestable in almost every respect. Deery insists that 'sugar is heavily incriminated as the major cause of dental caries'. How can this opinion be sustained in view of the fact that the recent huge changes in caries scores in western populations, the highest falls in history, occurred with no decrease in sugar intake? Next, there is the question, which stems from views advanced in the COMA report, namely -would a major fall in sugar intake alone, say by 20-25%, result in a significant fall in caries scores? While sugar certainly is an influencing factor, there must be a clear distinguishing between correlations of variables, and a specific cause and effect sequence. The results of the Vipeholm and Turku studies cited by Deery, although interesting, have limited bearing on this particular issue. Likewise, the phenomenon of rising caries scores with westernization of diet and other aspects of lifestyle (Deery mentions the Eskimos
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Journal of the Royal Society of Medicine Volume 85 June 1992
and Tristan da Cuhna islanders), these changes do not provide answers to the question at issue. We remain sceptical that a significant fall in caries occurrence would follow a fall in sugar intake. May we reiterate (i) that the observations made by Rugg-Gunn et alt1, by Sundin2, as well as by ourselves3, indicate that sugar intake explains only a minuscule proportion, 5-10%, ofthe variance in caries experience which prevail, between individuals and between communities; (ii) that no prospective study has been undertaken ofthe long-term effects of a fall in sugar intake alone, of the magnitude indicated, on caries scores; and (iii) that the over-claiming and over-blaming of specific dietary components associated with disorders and diseases (whether such concerns sugar intake and caries4, salt intake and hypertension5, or fat intake and coronary heart disease and diet-related cancers6), such attitudes and responses are considered as likely to prejudice the advance of the cause of public health. A R P WALKER
Human Biochemistry Research Unit Department of Tropical Diaeases School of Pathology of the University of the Witwatersrand, and the South African Institute for Medical Research PO Box 1038, Johannesburg P E CLEATON-JONES Medical Research Council Dental Research Institute Universit-y of the Witwatersrand Johannesburg, PO Wits, 2050 South Africa
References 1 Rugg-Gunn AJ, Hackett AF, Appleton DR, et aL Relationships between dietary habits and caries increment assessed over 2 years in 405 English adolescent schoolchildren. Arch Oral Biol 1984;29:983-92 2 Sundin B. Caries and consumption of sweets. University of Lund: D. Odont Thesis, 1990 3 Cleaton-Jones P, Richardson BD, Sinwel RW, et aL Dental caries and sucrose intake in five South African pre-school groups. Community Dent Oral Epidemiol 1984;12:381-5 4 Sheiham A. Why free sugars consumption should be below 15 kg per person per year in industrialised countries: The Dental Evidence. Br Dent J 1991;171: 63-5 5 Anastos K, Charney P, Charon RA, et al. Hypertension in women: what is really known? Ann Intern Med 1991;115:287-93 6 Skrabanek P, McCormick J. Prevention of coronary artery disease. N Engl J Med 1991;325;203-5
Warts and all Dr Burns is to be commended for the wit, as well as the wisdom, in his article (January 1992 JRSM, p 37). His catalogue of treatments for the verrucous disorder omitted, however, one modality that may continue to have its advocates - suggestion. Back in the 1940s and 1950s, a New York paediatrician named Hermann Vollmer claimed great success in treating children's warts by forceful suggestion abetted by blue lights and the like. Of course most, if not all, of the 'folk' remedies Burns describes would have rested on their suggestive value, but Vollmer's method was explicit, using the aura of 'science' as its fulcrum. Perhaps others have devised similar techniques. AARON H ESMAN Department of Psychiatry Payne Whitney Psychiatric Clinic The New York Hospital - Cornell Medical Center 525 East 68th Street, New York NY 10021, USA
Inhalation therapy in asthma As an astbma sufferer the article on inhalation therapy in asthma by Di Benedetto and Clarke (January 1992 JRSM, p 3) was of interest. They observed that the ideal inhalation technique combines slow, deep inhalation with about 10 seconds ofbreath holding'. Their discussion of the advantages and disadvantages of the three types of delivery systems used to deliver therapeutic aerosols (metered dose inhalers, dry powder devices and nebulisers) and the patients' ability to use them correctly, failed to highlight the overriding factor in the effectiveness of the delivery system employed, that is the capability of the patient. Unless a physician has suffered from asthma he/she cannot easily relate to the symptoms. The closest analogy that mimics the breathlessness an asthmatic experiences is swimming underwater and feeling the need to inhale deeply before reaching the surface. The swimmer experiences breathlessness and panic similar to that experienced by an asthmatic. During an attack it is difficult and distressing to inhale deeply or hold one's breath. I only have mild attacks which I control with salbutamol. However, even knowing that salbutamol brings relief and that my pulse rate is not abnormally high, holding my breath whilst breathless produces a sensation of panic. As a fit and healthy individual of 31 with a logical and rational approach to the causes and treatment of asthma I doubt my inability to perform the ideal inhalation technique is unique. Therefore there must be many asthmatics, with a more debilitating form of asthma, who are unable to receive the recommended dose from a delivery system because their inhalation capability is severely compromised. SARAH WATSON JAMES 6a Rowallan Road Fuiham, London SW6 6AG Reference 1 Newman SP, Clark SW. The proper use of metered dose inhalers. Chest 1984;86:342-4
The authors reply below: In our Editorial we have stated that'... it is much more difficult to inhale an aerosol than to take a pill.' We have also reported that about 50% of asthmatics might use their inhalers incorrectly. Miss Watson James refers to the difficulty of using an inhaler during an asthmatic attack, of which we have observed many. The possibility of patient error during the inhalation manoeuvre does not mean that the ideal method for optimizing lung deposition should not be taught. Moreover, the 'swimmer panic' does not apply to maintenance treatment with, for example, inhaled steroids. We are only too well aware that inhalation treatment is difficult, but this does not deter us from trying to achieve maximum results with minimum side effects. As far as bronchodilators and metered dose inhalers (MDIs) are concerned, our group has shown in the past that the percentage change in FEV1 15 min after inhaling 500 itg terbutaline sulphate from an MDI was +29.5% with a slow inhaled flow rate and a breath-holding pause of 10 seconds. The same group of patients still showed improvement in FEV1 (+20%) with fast inhaled flow rate and a breath-holding pause of only 4 seconds1. The real issue is therefore to increase the
Letters to the Editor Preference is given to letters commenting on contributions recently published in the JRSMi They should not exceed
300 words and should be typed double-spaced.
Haemorheological treatment of ischaemia - facts or fancy? With reference to the editorial by Ernst (November 1991 JRSM, p 639) we suggest that this article has less emphasis on facts than fancy. There are a number of inaccuracies and omissions which we feel require correction. The author suggests that enhancing blood fluidity is recommended if vessel damage cannot be repaired, but fails to make the significant differentiation between micro and macrocirculatory pathophysiology. Current concepts of haemorheology are also studiously avoided. It is now accepted that events within the microcirculation determine outcome in ischaemia to a large extent. While it is true that red blood cells affect blood viscosity in the macrocirculation, this is not true of the microcirmulation. The main determinant of blood flow in capillaries (5-10 zm diameter) is the pressure gradient and the passage of larger cells, ie white blood cells. It has also been shown that low flow states increase interaction between leukocytes and vessel endothelium causing local perfusion defects, resulting in ischaemic damagel'2. Therefore, manipulation ofwhite cell function is thought to be of greater relevance than red cell deformability. The author is correct in stating that many drugs alter red cell deformability, but it is not surprising that mostly they have no clinical effect. One of the drugs showing good clinical results is pentoxifylline (Trental, Hoechst), whose principal method of action is not due to increased red cell deformability, but rather to actions on the white cell membrane3. Similarly, the vasodilatatory actions of these drugs contribute little when a system is maximally vasodilated. Other drugs, eg prostanoids, modify WBC behaviour and have been shown to have a beneficial clinical effect in critical ischaemia, but have not been mentioned by the author4. He then suggests that lowering plasma fibrinogen may be 'the most attractive haemorheological concept'. This statement is made without any supporting clinical evidence, and the theoretical basis is unsound as we have already stated that red cell aggregation is not the most important factor in microcirculatory flow. It is, therefore, unlikely to be 'the most valuable method of enhancing the flow properties of blood'. Finally, his statement that peripheral arterial occlusive disease (PAOD) can be treated successfully by rheological means is yet unproven in any useful clinical setting, though we would agree that research into pharmacological approaches offers potential benefits, which are now starting to be realized5'6. DAVID SHIELDS Department of Surgery SANJEEV SARINr The Middlesex Hospital, London W1N 8AA References 1 Nash GB, Thomas PRS, Dormandy JA. Abnormal flow properties of white blood cells in patients with severe ischaemia of the leg. BMJ 1988;296:1699-1701
2 Nees S, Schonharting M. Role of different blood cell types in blood rheology. In: Mandell GL, Novick WJ, eds. Pentoxifylline and leukocyte function. Hoechst-Roussel, 1987:105-14 3 Armstrong M, Needham D, Hatchell DL, Nunn RS. Effect of pentoxifylline on the flow of polymorphonuclear leukocytes through a model capillary. Angiology 1990; 41:253-62 4 de Gaetano G, Vertele V, Cerletti C. Mechanism of action and clinical use of prostanoids. In: Dormandy JA, Stock G, eds Critical leg ischaemia its pathophysiology and management. Berlin: Springer-Verlag, 1990:117-37 5 Colgan M-P, Dormandy JA, Jones PW, Schraibman IG, Shanik DG, Young RAL. Oxpentifylline treatment of venous ulcers of the leg. BMJ 1990;300:972-5 6 Lindgarde F, Jelnes R, Bjorkman H, et aL Conservative drug treatment in patients with moderately severe chronic occlusive peripheral arterial disease. Circulation
1989;80:1549-56 Do not resuscitate I was interested in McNeil's poem on the 'Do Not Resuscitate' order (August 1991 JRSM, p 512). This reminded me of a teaching hospital physician in Sydney who had recently retired. He had let it be known he did not want to be resuscitated, but when he had a cardiac arrest in another physician's surgery, cardiac massage was undertaken and he was revived. This physician went on for many years thereafter, with full mental and physical capacity and even became a computer enthusiast. He eventually did die but did not linger on into painful senility. There is a big difference from a resuscitation of 'ancient, suffering wrecks' and those who are, apart from their cardiac condition, in good physical and mental health. Methinks those who are fit but do not want to be resuscitated have made the ancient mistake of considering the heart to be the seat of the emotions. Of course, if the resuscitation is only partly successful, ones medical attendants should not be too tardy in turning off the machine! K B ORR 24 Belgrave Street Kogarah 2217, Australia
The COMA report: sugars and dental caries The views and interpretations expressed by Deery (October 1991 JRSM, p 635), in response to our letter (May 1991 JRSM, p 320), call for comment, since they are contestable in almost every respect. Deery insists that 'sugar is heavily incriminated as the major cause of dental caries'. How can this opinion be sustained in view of the fact that the recent huge changes in caries scores in western populations, the highest falls in history, occurred with no decrease in sugar intake? Next, there is the question, which stems from views advanced in the COMA report, namely -would a major fall in sugar intake alone, say by 20-25%, result in a significant fall in caries scores? While sugar certainly is an influencing factor, there must be a clear distinguishing between correlations of variables, and a specific cause and effect sequence. The results of the Vipeholm and Turku studies cited by Deery, although interesting, have limited bearing on this particular issue. Likewise, the phenomenon of rising caries scores with westernization of diet and other aspects of lifestyle (Deery mentions the Eskimos
365
366
Journal of the Royal Society of Medicine Volume 85 June 1992
and Tristan da Cuhna islanders), these changes do not provide answers to the question at issue. We remain sceptical that a significant fall in caries occurrence would follow a fall in sugar intake. May we reiterate (i) that the observations made by Rugg-Gunn et alt1, by Sundin2, as well as by ourselves3, indicate that sugar intake explains only a minuscule proportion, 5-10%, ofthe variance in caries experience which prevail, between individuals and between communities; (ii) that no prospective study has been undertaken ofthe long-term effects of a fall in sugar intake alone, of the magnitude indicated, on caries scores; and (iii) that the over-claiming and over-blaming of specific dietary components associated with disorders and diseases (whether such concerns sugar intake and caries4, salt intake and hypertension5, or fat intake and coronary heart disease and diet-related cancers6), such attitudes and responses are considered as likely to prejudice the advance of the cause of public health. A R P WALKER
Human Biochemistry Research Unit Department of Tropical Diaeases School of Pathology of the University of the Witwatersrand, and the South African Institute for Medical Research PO Box 1038, Johannesburg P E CLEATON-JONES Medical Research Council Dental Research Institute Universit-y of the Witwatersrand Johannesburg, PO Wits, 2050 South Africa
References 1 Rugg-Gunn AJ, Hackett AF, Appleton DR, et aL Relationships between dietary habits and caries increment assessed over 2 years in 405 English adolescent schoolchildren. Arch Oral Biol 1984;29:983-92 2 Sundin B. Caries and consumption of sweets. University of Lund: D. Odont Thesis, 1990 3 Cleaton-Jones P, Richardson BD, Sinwel RW, et aL Dental caries and sucrose intake in five South African pre-school groups. Community Dent Oral Epidemiol 1984;12:381-5 4 Sheiham A. Why free sugars consumption should be below 15 kg per person per year in industrialised countries: The Dental Evidence. Br Dent J 1991;171: 63-5 5 Anastos K, Charney P, Charon RA, et al. Hypertension in women: what is really known? Ann Intern Med 1991;115:287-93 6 Skrabanek P, McCormick J. Prevention of coronary artery disease. N Engl J Med 1991;325;203-5
Warts and all Dr Burns is to be commended for the wit, as well as the wisdom, in his article (January 1992 JRSM, p 37). His catalogue of treatments for the verrucous disorder omitted, however, one modality that may continue to have its advocates - suggestion. Back in the 1940s and 1950s, a New York paediatrician named Hermann Vollmer claimed great success in treating children's warts by forceful suggestion abetted by blue lights and the like. Of course most, if not all, of the 'folk' remedies Burns describes would have rested on their suggestive value, but Vollmer's method was explicit, using the aura of 'science' as its fulcrum. Perhaps others have devised similar techniques. AARON H ESMAN Department of Psychiatry Payne Whitney Psychiatric Clinic The New York Hospital - Cornell Medical Center 525 East 68th Street, New York NY 10021, USA
Inhalation therapy in asthma As an astbma sufferer the article on inhalation therapy in asthma by Di Benedetto and Clarke (January 1992 JRSM, p 3) was of interest. They observed that the ideal inhalation technique combines slow, deep inhalation with about 10 seconds ofbreath holding'. Their discussion of the advantages and disadvantages of the three types of delivery systems used to deliver therapeutic aerosols (metered dose inhalers, dry powder devices and nebulisers) and the patients' ability to use them correctly, failed to highlight the overriding factor in the effectiveness of the delivery system employed, that is the capability of the patient. Unless a physician has suffered from asthma he/she cannot easily relate to the symptoms. The closest analogy that mimics the breathlessness an asthmatic experiences is swimming underwater and feeling the need to inhale deeply before reaching the surface. The swimmer experiences breathlessness and panic similar to that experienced by an asthmatic. During an attack it is difficult and distressing to inhale deeply or hold one's breath. I only have mild attacks which I control with salbutamol. However, even knowing that salbutamol brings relief and that my pulse rate is not abnormally high, holding my breath whilst breathless produces a sensation of panic. As a fit and healthy individual of 31 with a logical and rational approach to the causes and treatment of asthma I doubt my inability to perform the ideal inhalation technique is unique. Therefore there must be many asthmatics, with a more debilitating form of asthma, who are unable to receive the recommended dose from a delivery system because their inhalation capability is severely compromised. SARAH WATSON JAMES 6a Rowallan Road Fuiham, London SW6 6AG Reference 1 Newman SP, Clark SW. The proper use of metered dose inhalers. Chest 1984;86:342-4
The authors reply below: In our Editorial we have stated that'... it is much more difficult to inhale an aerosol than to take a pill.' We have also reported that about 50% of asthmatics might use their inhalers incorrectly. Miss Watson James refers to the difficulty of using an inhaler during an asthmatic attack, of which we have observed many. The possibility of patient error during the inhalation manoeuvre does not mean that the ideal method for optimizing lung deposition should not be taught. Moreover, the 'swimmer panic' does not apply to maintenance treatment with, for example, inhaled steroids. We are only too well aware that inhalation treatment is difficult, but this does not deter us from trying to achieve maximum results with minimum side effects. As far as bronchodilators and metered dose inhalers (MDIs) are concerned, our group has shown in the past that the percentage change in FEV1 15 min after inhaling 500 itg terbutaline sulphate from an MDI was +29.5% with a slow inhaled flow rate and a breath-holding pause of 10 seconds. The same group of patients still showed improvement in FEV1 (+20%) with fast inhaled flow rate and a breath-holding pause of only 4 seconds1. The real issue is therefore to increase the
