815
degrees. Studd states that there are women who self-medicate with extra oestrogen tablets or oestradiol patches, which confirms that oral and transdermal medication also need to be studied. Dr Ginsburg feels misquoted when we wrote that "some doctors advocate offering HRT to all women". She had written about a proposed trial of HRT that "did not address the crucial issues: Why were only 9% of the patients in their study receiving menopausal instead of advocating yet more trials ... an therapy? epidemiological unit could well ask why ... 91 % of British women are missing out on treatment that reduces mortality and morbidity and improves the quality of life".’ If, in summarising, we have misrepresented her view, we apologise. We did not suggest that doctors should tolerate patients’ suffering, or that clinical practice should be changed and oestrogen withdrawn. Indeed, if dependence is shown to exist, caution should be exerted when stopping. We merely pointed to some worrying facts about HRT prescribing and formulated a model that could explain them. Our purpose was to alert physicians to a possible side-effect that they might not otherwise recognise, so that cases, if they occur, could be reported to adverse reactions monitoring systems. The medical community should remain cautious while awaiting both proper scientific research that confirms or refutes the dependence hypothesis and the epidemiological consensus on long-term oestrogen therapy. These will provide two more important considerations when weighing the risk-benefit calculation, as should always be done when prescribing powerful drugs. ...
Department of Obstetrics and Gynaecology, University College and Middlesex School of Medicine,
University College London, London WC1E 6HX, UK
SUSAN BEWLEY
Department of Addictive Behaviour, St George’s Hospital, London
THOMAS BEWLEY
1.
Ginsburg J, Hardiman P, Okolo S, Whitehead M. Hormone replacement therapy in 302: 1601-02. general practice. Br Med 1991; J
Björk-Shiley valves MR,—Ur van der (jrraal and colleagues’ paper (reb 1, p 2.) /) is a useful contribution to the debate on the reliability of Bjork-Shiley valves. Unfortunately, there is no perfect artificial heart valve and consideration of such an infrequent complication as strut fracture requires a large population for adequate statistical analysis and consequent clinical recommendations. This is impossible in most personal series, and even in this ambitious national study, subgroup size remains, at times, inadequate-eg, detailed analysis is done on a cohort of only 14 group 1 70° valves over eight years. There are also inconsistent recommendations for reoperation. Consideration of prophylactic reoperation is recommended for patients with large 60° valves but not, apparently, for those with small 70° prostheses, though the latter had a higher fracture rate in this series (fig 2). For the public peace of mind perspective is necessary. Of the total 695 (30%) deaths during the follow-up period only 3-4% were attributed to strut fracture. I and colleagues have for some years been analysing developments from the best information available. In 1987 we recommended consideration of reoperation, on an individual basis, of patients with group 1 70° CC valves.! Recently we completed a detailed analysis of 831 70° CC valves (279 patients in this high-risk group in the Dutch study) implanted in five centres. Using many variations of the Cox multiple regression analysis with nine independent variables, we found that valve size was the only highly significant factor associated with strut fracture in a particular valve group. Once valve size was considered, neither age nor valve position were significant in strut fracture.2 When considering prophylactic reoperation to replace valves at risk, one must consider patients individually, weighing factors such as fracture risk, life expectation, risks of reoperation, and the increased morbidity and complication rate of prosthetic valves in the first year. We agree that these considerations should be applied to patients with 70° CC valves of size 29 mm or greater irrespective of whether the valve is aortic or mitral. From all available information, though not specifically considered in our study, we would not extend these considerations to 60° CC valves.
We agree that patients suspected of Bjork-Shiley valve failure "should be referred without delay to a cardiothoracic centre"; this complication, though rare, is a diagnostic and surgical emergency. Royal Brompton and National Heart Hospital, London SW3 6NP, UK
GRAEME BENNETT
Horstkotte D, Bennett J, et al. The Björk-Shiley 70 degree prosthesis strut fracture problem (present status of information). Thorac Cardiovasc Surg 1987; 2: 71-77. 2. Ericsson A, Lindblom D, Semb G, et al. Strut fracture with the Bjork-Shiley 70° convexo-concave valve, an international multi-institutional follow-up study. Eur J Cardiothoracic Surg (in press).
1. Ostermeyer J,
convexo-concave
Stridor and focal laryngeal dystonia SIR,-We have seen a 5-year-old boy with symptoms similar to those described by Dr Marion and her colleagues (Feb 22, p 457). A
life-threatening stridor developed suddenly and he was referred to our casualty department with the diagnosis of acute epiglottitis, which seemed likely at first. However, detailed questioning of the mother revealed that he had been given metoclopramide for 48 hours because of vomiting. A presumptive diagnosis of druginduced stridor and pharyngolaryngeal dystonia was confirmed by slow intravenous injection of ethybenztropin (1 mg); this freed the patient immediately from his distressing symptoms. The fever and vomiting proved to be due to viral infection. Three of the six patients reported by Marion et al presented, apart from stridor, with multifocal dystonia (blepharospasm 3, spasmodic torticollis 2, and arm dystonia 1). Multifocal dystonia, especially concomitant spasmodic torticollis, is highly suggestive of druginduced dystonic reactions. Dystonic reactions induced by antiemetics, neuroleptics, and the like are more frequent in young patients but they do occur in adults as welland they are confusing symptoms since they can mimic several diseases. 1,3 Identifying dystonic reactions as such is especially difficult where only one muscle or muscle group is involved, in our experience. Any patient presenting with dystonia, including stridor and focal laryngeal dystonia, should be asked about medication. Experience has taught us to name potential dystonia inducers since some are kept in the kitchen drawer as "digestives" and are no longer considered as medicines. Department of Paediatrics, University Hospital Gasthuisberg, University of Leuven, 3000 Leuven, Belgium
MARIA CASTEELS-VAN DAELE EPHREM EGGERMONT
1. Casteels-Van Daele M, Jaeken J, Van Der Schueren P, Zimmermann A, Van Den Bon P. Dystonic reactions in children caused by metoclopramide. Arch Dis Child 1970, 45: 130-33. 2. Martindale. The
extra
pharmacopoeia, 28th ed.
London. Pharmaceutical Press, 1982:
964, 966, 1532. 3. Casteels-Van Daele M. Paroxysmal torticollis in infancy.
Pruritus after
Am J Dis Child 1970; 120: 88.
cardiopulmonary bypass
SIR,—The recognised complications of open heart surgeryl do include pruritus. Towards the end of 1989 one of us (C.W.) noted that after bypass surgery several patients had severe pruritus not
of the upper trunk. Subsequently 14 such cases were identified and we describe the clinical findings and our attempts to identify the cause.
patients were seen in the department of dermatology and 3 interviewed by telephone. A questionnaire was completed by interviewers (A.J.C., C.W., M.R.) recording medical and family history, outcome of surgery, and .details of the itch. All patients completed an Eysenck personality questionnaire (EPQ). 6 of the patients with itch at the time of interview agreed to further investigations, which included measurement of blood flow by laser Doppler velocimetry,2 resting skin temperature with a thermocouple, erythema by reflectance erythemometry, and the effect of stimulating blood flow with a topical rubefacient by laser Doppler velocimetry. Itch threshold was assessed by applying, after scarification, 2, 4, 8, 16, and 32 Ilg/ml concentrations of histamine acid phosphate monohydrateHistamine responsiveness was evaluated by measuring flare areas produced after 20 min by 11
were
816
CLINICAL DETAILS
*Operations were done between February, 1988, and July, operations CABG
=
AV R = aortic valve
replacement
coronary artery
bypass graft, MVR
=
1990 tin months after mitral valve replacement.
intracutaneous injection of 20 gg histamine by planimetry (Optimax V image analyser; Analytical Measuring Systems, Cambridge). Thresholds for dermographism were also measured.’ 4 mm diameter skin samples were removed from the affected upper trunk and unaffected forearm and stained for mast cells, the evaluation being without knowledge of the source of the specimen. The itch began 1-6 weeks after bypass surgery and was at its worst by 3 months on average; it resolved after 4-24 months. The itch was mainly seen on the upper trunk (table); it was episodic, bouts lasting 15 min or so, and was precipitated by towelling after bathing. Most patients found the itch embarrassing but only 9 had sought medical advice. Neither emollients nor antihistamines were helpful. There was a history of atopy in only 2 patients. Postoperatively most patients were put on aspirin and dipyridamole but no relief from the itch was noticed after withdrawal of these agents. Only 3 patients had high neurotic scores (EPQ). Examination showed no evidence of a primary dermatosis and an exaggerated dermographic response could not be elicited. Neither resting skin laser doppler velocimetry nor temperature and erythema measurement revealed evidence of a perfusion abnormality in the affected skin. Nor did responsiveness to stimulation with the rubefacient differ between affected and control sites. There was a diminished itch threshold to histamine in affected truncal skin (fig 1) but the response to intradermal histamine did not differ (fig 2). The normality of the dermographic response was confirmed by dermographometry. Histological examination revealed no evidence of an inflammatory cell infiltrate or altered epidermal structure, and there was no alteration in mast cell numbers. All these patients had had a thoracotomy and we thought that this might have affected truncal skin blood flow. However, our tests did not support this view. Thoracotomy not associated with
Fig 2-Flare area after intracutaneous histamine.
cardiopulmonary bypass has not been found to be complicated by pruritus, in the experience of cardiothoracic surgeons in Cardiff, The itch threshold to histamine was diminished but this did not seem to reflect a general upregulation of histamine receptors because wheal and flare responsiveness and dermographism were normal. Nor did the itch seem to be a manifestation of subclinical inflammation, and nor could medicaments be implicated. The pruritus may be one of the many subtle features of neurological
dysfunction following cardiopulmonary bypass.S Clinically, the itch in these patients resembles aquagenic pruritus6 but it can be distinguished by its distribution, spontaneous regression, and the generally stable personality of those affected. Discussion with other UK cardiothoracic centres suggests that itch following cardiopulmonary bypass is not unique to Cardiff, but that it has been overlooked. A formal assessment is underway.
Departments of Dermatology and Cardiology, University of Wales College of Medicine, Cardiff CF4 4XN, UK
ANDREW J. CARMICHAEL R. MARKS CLIVE WESTON MARK RAMSEY MICHAEL STEPHENS
Kuan P, Bernstein SB, Ellestad MH. Coronary artery bypass surgery morbidity. J Am Coll Cardiol 1984; 3: 1391-97. 2 Kohli R, Archer WI, Po ALW. Laser velocimetry for non-invasive assessment of the percutaneous absorption of nicotinates. Int J Pharm 1987, 36: 91-98. 3. Shuttleworth D, Hill S, Marks R, Connelly DM. Relief of experimentally induced pruritus with a novel eutectic mixture of local anaestheic agents. Br J Damatol 1988; 119: 535-40. 4. Edwards C, Marks R, Shall L, Black D, Caunt A. A new integrated automatic dermographometer to monitor skin reactivity to linear trauma. Bioeng Skin 1986;2: 1.
191-201 5. Shaw PJ, Bates
6.
D, Cartlidge NEF, et al. An analysis of factors predisposing to neurological injury in patients undergoing coronary artery bypass operations. Quart J Med 1989; 72: 633-46. Steinman HK, Greaves MW. Aquagenic pruritus. J Am Acad Dermatol 1985; 13: 91-95.
Painless blood sampling for self blood
glucose measurement
Fig 1-Itch threshold to percutaneous histamine.
SIR,-For self blood glucose monitoring finger sampling is usual but pain receptors are concentrated at the fingertip, and diabetic patients are unlikely to comply with regimens that require frequent sampling. I describe here a new, painless system of sampling from the abdominal wall. This method has been studied by comparing the difference in pain and also blood glucose for fmger and for abdominal sampling. 74 patients (male 45, female 29) with diabetes were studied at an outpatient clinic of Saiseikai Central Hospital. 66 had non-insulindependent diabetes, ages ranged from 19 to 79 years (mean 54), duration of diabetes from 0-1 to 40 years (12-5). 38 patients had retinopathy and 28 had persistent proteinuria. 21 patients were on diet and exercise alone, 17 were taking oral hypoglycaemic agents, and 36 were on insulin.
degrees. Studd states that there are women who self-medicate with extra oestrogen tablets or oestradiol patches, which confirms that oral and transdermal medication also need to be studied. Dr Ginsburg feels misquoted when we wrote that "some doctors advocate offering HRT to all women". She had written about a proposed trial of HRT that "did not address the crucial issues: Why were only 9% of the patients in their study receiving menopausal instead of advocating yet more trials ... an therapy? epidemiological unit could well ask why ... 91 % of British women are missing out on treatment that reduces mortality and morbidity and improves the quality of life".’ If, in summarising, we have misrepresented her view, we apologise. We did not suggest that doctors should tolerate patients’ suffering, or that clinical practice should be changed and oestrogen withdrawn. Indeed, if dependence is shown to exist, caution should be exerted when stopping. We merely pointed to some worrying facts about HRT prescribing and formulated a model that could explain them. Our purpose was to alert physicians to a possible side-effect that they might not otherwise recognise, so that cases, if they occur, could be reported to adverse reactions monitoring systems. The medical community should remain cautious while awaiting both proper scientific research that confirms or refutes the dependence hypothesis and the epidemiological consensus on long-term oestrogen therapy. These will provide two more important considerations when weighing the risk-benefit calculation, as should always be done when prescribing powerful drugs. ...
Department of Obstetrics and Gynaecology, University College and Middlesex School of Medicine,
University College London, London WC1E 6HX, UK
SUSAN BEWLEY
Department of Addictive Behaviour, St George’s Hospital, London
THOMAS BEWLEY
1.
Ginsburg J, Hardiman P, Okolo S, Whitehead M. Hormone replacement therapy in 302: 1601-02. general practice. Br Med 1991; J
Björk-Shiley valves MR,—Ur van der (jrraal and colleagues’ paper (reb 1, p 2.) /) is a useful contribution to the debate on the reliability of Bjork-Shiley valves. Unfortunately, there is no perfect artificial heart valve and consideration of such an infrequent complication as strut fracture requires a large population for adequate statistical analysis and consequent clinical recommendations. This is impossible in most personal series, and even in this ambitious national study, subgroup size remains, at times, inadequate-eg, detailed analysis is done on a cohort of only 14 group 1 70° valves over eight years. There are also inconsistent recommendations for reoperation. Consideration of prophylactic reoperation is recommended for patients with large 60° valves but not, apparently, for those with small 70° prostheses, though the latter had a higher fracture rate in this series (fig 2). For the public peace of mind perspective is necessary. Of the total 695 (30%) deaths during the follow-up period only 3-4% were attributed to strut fracture. I and colleagues have for some years been analysing developments from the best information available. In 1987 we recommended consideration of reoperation, on an individual basis, of patients with group 1 70° CC valves.! Recently we completed a detailed analysis of 831 70° CC valves (279 patients in this high-risk group in the Dutch study) implanted in five centres. Using many variations of the Cox multiple regression analysis with nine independent variables, we found that valve size was the only highly significant factor associated with strut fracture in a particular valve group. Once valve size was considered, neither age nor valve position were significant in strut fracture.2 When considering prophylactic reoperation to replace valves at risk, one must consider patients individually, weighing factors such as fracture risk, life expectation, risks of reoperation, and the increased morbidity and complication rate of prosthetic valves in the first year. We agree that these considerations should be applied to patients with 70° CC valves of size 29 mm or greater irrespective of whether the valve is aortic or mitral. From all available information, though not specifically considered in our study, we would not extend these considerations to 60° CC valves.
We agree that patients suspected of Bjork-Shiley valve failure "should be referred without delay to a cardiothoracic centre"; this complication, though rare, is a diagnostic and surgical emergency. Royal Brompton and National Heart Hospital, London SW3 6NP, UK
GRAEME BENNETT
Horstkotte D, Bennett J, et al. The Björk-Shiley 70 degree prosthesis strut fracture problem (present status of information). Thorac Cardiovasc Surg 1987; 2: 71-77. 2. Ericsson A, Lindblom D, Semb G, et al. Strut fracture with the Bjork-Shiley 70° convexo-concave valve, an international multi-institutional follow-up study. Eur J Cardiothoracic Surg (in press).
1. Ostermeyer J,
convexo-concave
Stridor and focal laryngeal dystonia SIR,-We have seen a 5-year-old boy with symptoms similar to those described by Dr Marion and her colleagues (Feb 22, p 457). A
life-threatening stridor developed suddenly and he was referred to our casualty department with the diagnosis of acute epiglottitis, which seemed likely at first. However, detailed questioning of the mother revealed that he had been given metoclopramide for 48 hours because of vomiting. A presumptive diagnosis of druginduced stridor and pharyngolaryngeal dystonia was confirmed by slow intravenous injection of ethybenztropin (1 mg); this freed the patient immediately from his distressing symptoms. The fever and vomiting proved to be due to viral infection. Three of the six patients reported by Marion et al presented, apart from stridor, with multifocal dystonia (blepharospasm 3, spasmodic torticollis 2, and arm dystonia 1). Multifocal dystonia, especially concomitant spasmodic torticollis, is highly suggestive of druginduced dystonic reactions. Dystonic reactions induced by antiemetics, neuroleptics, and the like are more frequent in young patients but they do occur in adults as welland they are confusing symptoms since they can mimic several diseases. 1,3 Identifying dystonic reactions as such is especially difficult where only one muscle or muscle group is involved, in our experience. Any patient presenting with dystonia, including stridor and focal laryngeal dystonia, should be asked about medication. Experience has taught us to name potential dystonia inducers since some are kept in the kitchen drawer as "digestives" and are no longer considered as medicines. Department of Paediatrics, University Hospital Gasthuisberg, University of Leuven, 3000 Leuven, Belgium
MARIA CASTEELS-VAN DAELE EPHREM EGGERMONT
1. Casteels-Van Daele M, Jaeken J, Van Der Schueren P, Zimmermann A, Van Den Bon P. Dystonic reactions in children caused by metoclopramide. Arch Dis Child 1970, 45: 130-33. 2. Martindale. The
extra
pharmacopoeia, 28th ed.
London. Pharmaceutical Press, 1982:
964, 966, 1532. 3. Casteels-Van Daele M. Paroxysmal torticollis in infancy.
Pruritus after
Am J Dis Child 1970; 120: 88.
cardiopulmonary bypass
SIR,—The recognised complications of open heart surgeryl do include pruritus. Towards the end of 1989 one of us (C.W.) noted that after bypass surgery several patients had severe pruritus not
of the upper trunk. Subsequently 14 such cases were identified and we describe the clinical findings and our attempts to identify the cause.
patients were seen in the department of dermatology and 3 interviewed by telephone. A questionnaire was completed by interviewers (A.J.C., C.W., M.R.) recording medical and family history, outcome of surgery, and .details of the itch. All patients completed an Eysenck personality questionnaire (EPQ). 6 of the patients with itch at the time of interview agreed to further investigations, which included measurement of blood flow by laser Doppler velocimetry,2 resting skin temperature with a thermocouple, erythema by reflectance erythemometry, and the effect of stimulating blood flow with a topical rubefacient by laser Doppler velocimetry. Itch threshold was assessed by applying, after scarification, 2, 4, 8, 16, and 32 Ilg/ml concentrations of histamine acid phosphate monohydrateHistamine responsiveness was evaluated by measuring flare areas produced after 20 min by 11
were
816
CLINICAL DETAILS
*Operations were done between February, 1988, and July, operations CABG
=
AV R = aortic valve
replacement
coronary artery
bypass graft, MVR
=
1990 tin months after mitral valve replacement.
intracutaneous injection of 20 gg histamine by planimetry (Optimax V image analyser; Analytical Measuring Systems, Cambridge). Thresholds for dermographism were also measured.’ 4 mm diameter skin samples were removed from the affected upper trunk and unaffected forearm and stained for mast cells, the evaluation being without knowledge of the source of the specimen. The itch began 1-6 weeks after bypass surgery and was at its worst by 3 months on average; it resolved after 4-24 months. The itch was mainly seen on the upper trunk (table); it was episodic, bouts lasting 15 min or so, and was precipitated by towelling after bathing. Most patients found the itch embarrassing but only 9 had sought medical advice. Neither emollients nor antihistamines were helpful. There was a history of atopy in only 2 patients. Postoperatively most patients were put on aspirin and dipyridamole but no relief from the itch was noticed after withdrawal of these agents. Only 3 patients had high neurotic scores (EPQ). Examination showed no evidence of a primary dermatosis and an exaggerated dermographic response could not be elicited. Neither resting skin laser doppler velocimetry nor temperature and erythema measurement revealed evidence of a perfusion abnormality in the affected skin. Nor did responsiveness to stimulation with the rubefacient differ between affected and control sites. There was a diminished itch threshold to histamine in affected truncal skin (fig 1) but the response to intradermal histamine did not differ (fig 2). The normality of the dermographic response was confirmed by dermographometry. Histological examination revealed no evidence of an inflammatory cell infiltrate or altered epidermal structure, and there was no alteration in mast cell numbers. All these patients had had a thoracotomy and we thought that this might have affected truncal skin blood flow. However, our tests did not support this view. Thoracotomy not associated with
Fig 2-Flare area after intracutaneous histamine.
cardiopulmonary bypass has not been found to be complicated by pruritus, in the experience of cardiothoracic surgeons in Cardiff, The itch threshold to histamine was diminished but this did not seem to reflect a general upregulation of histamine receptors because wheal and flare responsiveness and dermographism were normal. Nor did the itch seem to be a manifestation of subclinical inflammation, and nor could medicaments be implicated. The pruritus may be one of the many subtle features of neurological
dysfunction following cardiopulmonary bypass.S Clinically, the itch in these patients resembles aquagenic pruritus6 but it can be distinguished by its distribution, spontaneous regression, and the generally stable personality of those affected. Discussion with other UK cardiothoracic centres suggests that itch following cardiopulmonary bypass is not unique to Cardiff, but that it has been overlooked. A formal assessment is underway.
Departments of Dermatology and Cardiology, University of Wales College of Medicine, Cardiff CF4 4XN, UK
ANDREW J. CARMICHAEL R. MARKS CLIVE WESTON MARK RAMSEY MICHAEL STEPHENS
Kuan P, Bernstein SB, Ellestad MH. Coronary artery bypass surgery morbidity. J Am Coll Cardiol 1984; 3: 1391-97. 2 Kohli R, Archer WI, Po ALW. Laser velocimetry for non-invasive assessment of the percutaneous absorption of nicotinates. Int J Pharm 1987, 36: 91-98. 3. Shuttleworth D, Hill S, Marks R, Connelly DM. Relief of experimentally induced pruritus with a novel eutectic mixture of local anaestheic agents. Br J Damatol 1988; 119: 535-40. 4. Edwards C, Marks R, Shall L, Black D, Caunt A. A new integrated automatic dermographometer to monitor skin reactivity to linear trauma. Bioeng Skin 1986;2: 1.
191-201 5. Shaw PJ, Bates
6.
D, Cartlidge NEF, et al. An analysis of factors predisposing to neurological injury in patients undergoing coronary artery bypass operations. Quart J Med 1989; 72: 633-46. Steinman HK, Greaves MW. Aquagenic pruritus. J Am Acad Dermatol 1985; 13: 91-95.
Painless blood sampling for self blood
glucose measurement
Fig 1-Itch threshold to percutaneous histamine.
SIR,-For self blood glucose monitoring finger sampling is usual but pain receptors are concentrated at the fingertip, and diabetic patients are unlikely to comply with regimens that require frequent sampling. I describe here a new, painless system of sampling from the abdominal wall. This method has been studied by comparing the difference in pain and also blood glucose for fmger and for abdominal sampling. 74 patients (male 45, female 29) with diabetes were studied at an outpatient clinic of Saiseikai Central Hospital. 66 had non-insulindependent diabetes, ages ranged from 19 to 79 years (mean 54), duration of diabetes from 0-1 to 40 years (12-5). 38 patients had retinopathy and 28 had persistent proteinuria. 21 patients were on diet and exercise alone, 17 were taking oral hypoglycaemic agents, and 36 were on insulin.
