1443
17 between 2-4 and 11 (intermediate), and 26 1-1 than lower 1 (weak). 18 Ortho-ELISA positive samples (6 from each absorbance category) were also tested by Abbott ELISA and
(strongly reactive), RIBA:
ortho EL ISA + ve* Weak (6) Intermediate (6)
Abbott ELISA + ve 5 5 6
Strong
Chiron RIBA +
ve
0 1 6
*Cut-off value 0 451; +ve=positive.
16 samples were positive with the Abbott test and 7 with RIBA, 6 of which were strongly reactive with Ortho ELISA. The distribution
of absorbance values in Ortho ELISA was closely related to the distribution of anti-ENA ELISA vaues (r = 0-45; p =5x 10 - 6). Indeed, anti-ENA autoantibodies were found in 48 (81%) HCVpositive and 9 (26%) HCV-negative samples (Chi-square test
p< 10-6). Our
findings suggest
a relation between malaria and falseHCV results. The non-specific reacivity is probably attributable to antinuclear and other autoantibodies that arise in malaria patients.2 These can lead to false-positive reactions with HCV ELISA kits that are based on detection with an anti-IgG reagent, because of their high affinity for the solid phase.3We obtained closely similar results with Abbott and Ortho ELI SAs and found a close correlation between anti-ENA and anti-HCV optical density values. We showed false-positive tests only in intermediate and weakly reactive specimens. Our results therefore do not support Wong and colleagues’ suggestion that non-specificity can also arise in strongly reactive sera. Workers investigating HCV seroepidemiology in malarious regions should be aware of the possibility of false-positive reactions in order to establish a reliable profile of HCV antibody prevalence.
positive
This work was in part
supported by a grant from MURST, Project "Cirrosi
ed epatiti virali".
Institute for Tropical and Infectious Diseases, La Sapienza University, 00161 Rome, Italy
ANTONIO ACETI GLORIA TALIANI CARLO DE BAC ANTONIO SEBASTIANI
Manthorpe R, Bendixen G. Anti-ENA antibody in serum determined by ELISA-technique, description of method and recommended procedure. Allergy 1981; 36: 397-404. 2. Boonpucknavig S, Ekapanyakul. Autoantibodies in sera of Thai patients with Plasmodium falciparum infection. Clin Exp Immunol 1984; 58: 77-82. 3. Cafruny WA, Heruth DP, Jaqua MJ, Plagemann PGW. Immunoglobulins that bind to uncoated ELISA plate surfaces: appearance in mice during infection with lactate-dehydrogenase-elevating virus and in human anti-nuclear antibodypositive sera. J Med Virol 1986; 19: 175-86. 1. Struckmann J,
Cisapride and brittle asthma reflux disease (GORD) is fairly in chronic asthma1 and can be secondary to or aggravated by bronchodilator therapy. Oesophageal reflux contributes towards exacerbations of airflow obstruction in some asthmatics, though the mechanism is not clearControl of GORD in such patients can lead to substantial improvement in their asthma.3 Cisapride has been used successfully in the management of oesophageal reflux.1 As a prokinetic agent acting by the facilitation of cholinergic transmission in the myenteric plexus,s cisapride might affect other sites of cholinergic transmission, such as bronchial smooth muscle. We describe a chronic asthmatic whose asthma worsened after
SIR,-Gastro-oesophageal
common
cisapride. An
steroid-dependent asthma Her asthma was "brittle" with 20 hospital admissions in the preceding 12 months. Increased bronchial reactivity had been confirmed on bronchial challenge (PCj 0-09 mg/ml). Maintenance therapy included prednisolone 40 mg daily, inhaled salbutamol, inhaled beclamethasone 4000 fly daily, and oral theophylline (serum concentration 10-15 mg/1). Her asthma had been stabilised, with mean daily peak flow rates (PFR) of 4901/min (SD 23). She had confirmed disordered oesophageal motility and nocturnal pulmonary aspiration (radioisotope aspiration study), and ulcerative oesophagitis was found at 18-year-old
woman
with
severe
was admitted after an acute attack.
Peak flow rates before
(.) and after (*) cisapride.
gastroscopy. Antacids and an H2-receptor blocker were introduced, but symptoms of her reflux persisted and cisapride 10 mg thrice daily was introduced. Within 3 h of the first dose of cisapride, chest tightness and wheeze developed, and her PFR fell to 360 1/min. This pattern was also seen after the second dose. A total of four 10 mg doses were given before the drug was abandoned (figure). During the 48 hours of the cisapride trial the mean PFR was 435 1/min (42). On withdrawal of cisapride, PFR returned to baseline. It was considered unethical to rechallenge the patient once she had recovered. Asthma is not regarded as a contraindication for the use of cisapride.6 We believe that patients on cisapride with a history of asthma should be closely monitored. Although cisapride has been used in hospital patients with a history of respiratory disease,’ changes in expiratory flow rates have not been reported. The effect of cisapride on bronchial reactivity in healthy individuals and in asthmatics has not been described.
Sir Charles Gairdner Hospital, Nedlands, Perth, Western Australia
P. NOLAN M. PHILLIPS B. WILLIAMSON
1. Ekstrom T, Tibbling L.
Esophageal acid perfusion, airway function and symptoms in asthmatic patients with marked bronchial hyperactivity. Chest 1989; 96: 995-97. 2. Castell, DO. Asthma and gastroesophageal reflux. Chest 1989; 96: 2-3. 3. Perrin-Fayoue M. Long term results of surgical treatment for gastro-oesophageal reflux in asthmatic patients. Chest 1989; 96: 40-45. 4. Camilleri M, Malagehda J, Abell TL, Brown M, Hench V, Zinmeister A. Effect of six weeks of treatment with cisapride in gastroparesis and intestinal pseudoobstruction Gastroenterology 1989; 96: 704-12. 5. Tonini M, Galligan JJ, North RA. Effects of cisapride on cholinergic neurotesrismission and propulsive motility in the guinea pig ileum. Gastroenterology 1989; 96: 1257-64. 6. Drug Insert. Jansen-Cilag, 1990. 7. Malfroot A, Vandenplas Y, Verlinden M, Piepsz A, Dab I. Gastroesophageal reflux and unexplained chronic respiratory disease in infants and children. Pediatr Pulmonol 1987; 3: 208-13.
Low intraocular pressure in seasonal
affective disorder SIR,-Several psychophysiological abnormalities seem to be present in seasonal affective disorder (SAD).1 However, no exact biological basis for SAD is known. We have suggested a SADrelated lowering of ocular pressure.2.3 We have investigated intraocular pressure (IOP) in ten women with SAD (mean age 29 3 [SD 54]) and twelve female controls (27[4.8]). The women with SAD met DSM-III criteria for major depression, developing during the autumn or winter and improving in the spring, for at least two consecutive years. A score of 16 or more on the Hamilton rating scale for depression (HDRS) was required for entry to the study. The controls were hospital staff and none had had seasonal
depression. In both groups ocular examinations were normal, and most eyes emmetropic. All subjects gave written informed consent. IOP was measured four times 1 h apart, starting at 1600 h, with the were
1444
tonometer (Glaucon-Opticon). This time was chosen because winter depression is associated with a striking worsening of symptoms in the late afternoon, and because at this time IOP is stable in healthy subjects. All tonometric examinations were made during the late luteal phase of the menstrual cycle (days 20-25). The patients had higher HDRS scores in winter (February to December) than in summer (May to July) (20-7 [5’1] vs 2-6 [1’7]; p < 001). Patients had substantially lower mean (SEM) IOP values than controls in both seasons (winter 13 62 [0-43] vs 17 25 [051] mm Hg; summer 12 91 [0.39] vs 1485 [0.45] mm Hg; p < 001, Mann-Whitney U test). The difference in IOP values between women with SAD and the controls cannot be accounted for by non-specific factors such as age, time of day of ocular recordings, or phase of the menstrual cycle. Since the average IOP in the general population is higher in winter than in summer,4seasonal independence of abnormally low IOP values in a subgroup of winter depressives might be a trait characteristic of winter depression.
applanation
II Department of Psychiatry, School of Medicine in Gdansk, Gdansk-Wrzeszcz
ANDRZEJ STOJEK
Psychiatric Research Unit, 12 Wroclawska Street, 44-335 Jastrzebie-Zdroj, Poland
BOZENA KASPRZAK ANDRZEJ SLABIKOWSKI
1. Rosenthal
2.
NE, Sack DA, Gillin JCh, et al. Seasonal affective disorder. Arch Gen Psychiatry 1987; 41: 72-80. Stojek A, Bilikiewicz A. Bright artificial light lowers intraocular pressure and plasma sodium concentrations less in depressed patients than healthy controls. Plznen Lek Shorn 1988; 56: 157-60.
Stojek A, Kasprzak B, Bilikiewicz A. Changes in ocular humor dynamics in SAD patients after phototherapy. Paper presented at the 18th European conference on psychosomatic research. (August, 1990, Helsinki, Finland). 4. Blumenthal M, Blumenthal R, Peritz E, Best M. Seasonal variation in intraocular pressure. Am J Ophthalmol 1970; 69: 608-10. 3.
New drug
danger for children
SIR,-A worrying new drug danger to schoolchildren, first noted in the Netherlands and Switzerland, is starting to appear in the UK. Gifts of self-adhesive stickers, designed to be stuck on the skin as decoration, are being offered to children of all ages. After a warning from British Army headquarters in Germany, and since many service families live in the area, a Portsmouth primary school sent out a circular giving details of four drug-impregnated decorative stickers brought back to and circulated in the UK. A 15-year-old boy with adolescent behaviour difficulties attended an "acid house" party on the Isle of Wight. There was a suspicion that illegal drugs had been passed at the party, and he admitted that several types of drug-impregnated decorative stickers had been seen there and that in a few instances these had been attached to the entrance tickets. He did not admit to having or handling any of these stickers, and did not appear to have any
drug-related problems. So far the sitckers found are: (1) a blue star on white background, (2) a small token named "Window Pane" with motifs to cut out, and (3) a small card with the name "Rote Pyramide" (red pyramid) printed on it. Also there have been tiny coloured grains/seeds intended to be swallowed. The stickers are impregnated with LSD (lysergide), strychnine, and, possibly, a phenothiazine, some of which is absorbed through the skin even when the stickers are held in the hand. They may cause rapid and unpredictable reactions; a few children may get headaches, vomiting, hallucinations, and or fluctuating temperature. The aim is to cause dependency and therefore new customers for Europe’s illegal drug trade. The smaller the child the greater the relative dose absorbed and the greater the risk of symptoms. Symptoms are far more likely if the stickers are licked, as is sometimes advised. Sometimes the stickers are attached to tickets for acid house parties, which may be attended by children as young as 10 years who, in all innocence, go for the music. Parents, teachers, and doctors have a responsibility to identify and, as far as possible, to prevent these risks by publicity leading to greater awareness of the problem. Paediatric Department, St
Mary’s Hospital, Newport, Isle of Wight, PO30 5TG, UK
E. S. MUCKLOW
Digital clubbing SIR,-We wish to comment on your Oct 6 editorial on clubbing. We have studied clubbing in cyanotic heart disease, an entity in which the acropachy is constant and usually life-long,’ and in primary hypertrophic osteoarthropathy (HOA), in which the syndrome is not accompanied by any underlying illness.2 We agree that assessment of finger clubbing should be uniform so that groups of patients and/or responses to therapy can be compared; therefore, we have proposed the "digital index"3 as a simple measure of clubbing. It is reproducible and clearly distinguishes clubbing from the normal finger shape. While we agree that our fmdings with respect to bony changes in clubbed digits’ have not been confirmed by others, to our knowledge no one else has studied this systematically. The vascular changes of clubbing are not limited to vasodilatation: apart from excessive fibroblast proliferation, there is also structural vessel damage. Electronmicroscopic studies have shown endothelial cell injury.5 Our studies on pathogenesis showed normal circulating concentrations of growth hormone in both groups of patientsIn HOA, inflammatory and autoimmune changes are not found by conventional serology; therefore we proposed that a fibroblast growth factor could be responsible for the syndrome.6 This growth factor would normally be present in the central venous circulation and removed in the lung. Subsequently, Dickinson and Martin7 suggested that this growth factor could be platelet-derived. Their theory was based on a mathematical model proposed by Trowbridge et al,8 which suggested that in normal circumstances large platelets are fragmented in the lung. In patients with cardiogenic HOA we have found a bizarre platelet population with features that agree with the Trowbridge model 9 Thus, these data suggest that localised activation of platelet-endothelial cells, with the ensuing release of growth factor(s), is a key feature in the development of clubbing. The First International Workshop on HOA will be held in Dubrovnik, Yugoslavia, in September, 1991. It is hoped that this meeting will help to settle some of the controversies described here. Instituto Nacional de
Cardiologia
MANUEL MARTÍNEZ-LAVÍN CARLOS PINEDA
Ignacio Chávez, 14080 México D.F Mexico
M, Bobadilla M, Casanova JM, Attié F, Martinez M. Hypertrophic osteoarthropathy m cyanotic congenital heart disease; its prevalence and relationship to bypass of the lung. Arthritis Rheum 1982; 25: 1186-93. Martinez-Lavin M, Pineda C, Valdez T, et al. Primary hypertrophic
1. Martinez-Levin
2.
osteoarthropathy. Semin Arthritis Rheum 1988; 17: 156-62. Vazquez-Abad D, Pineda C, Martinez-Lavin M. Digital clubbing; a numerical assessment of the deformity. J Rheumatol 1989; 16: 518-20. 4. Pineda C, Fonseca C, Martinez-Lavin M. Radiologic vignette: the spectrum of soft tissue and skeletal abnormalities of hypertrophic osteoarthropathy. J Rheumatol 3.
1990; 17: 626-32. M, Cinti S, Morroni M,
et al. Pachydermoperiostosis (primary hypertrophic osteoarthropathy): report of a case with evidence of endothelial and
5. Matucci-Cerinic
connective involvement. Ann Rheum Dis 1989; 48: 240-46. 6. Martinez-Lavin M. Digital clubbing and hypertrophic osteoarthropathy: a unifying hypothesis. J Rheumatol 1987; 14: 6-8. 7. Dickinson CJ, Martin JF Megakaryocytes and platelet clumps as the cause of finger dubbing. Lancet 1987; ii. 1434-35. 8. Trowbridge EA, Martin JF, Slater DN. Evidence for a theory of physical fragmentation of megakaryocytes, impying that all platelets are produced in the pulmonary circulation. Thromb Res 1982; 28: 461-75. 9. Vazquez-Abad D, Martinez-Lavin M. Macrothrombocytes in the peripheral circulation of patients with cardiogenic hypertrophic osteoarthropathy. Clin Exp Rheumatol (in press).
Monocyte activation and increased procoagulant activity in unstable angina SIR,-Increased A
thrombin
formation
revealed
plasma concentrations (FPA) is
by raised
in unstable angina. 1-3 The causes and mechanisms of the enhanced thrombin formation are unknown. Since monocyte/macrophages are a characteristic component of the coronary atherosclerotic plaque in such patients,4-6 we investigated the role of monocytes in increased thrombin formation. We studied 28 patients with unstable angina, 18 with stable effort angina, and 30 controls matched for age. Patients with unstable angina had higher FPA plasma concentrations (mean 7-67 [0-59]
fibrinopeptide
common
17 between 2-4 and 11 (intermediate), and 26 1-1 than lower 1 (weak). 18 Ortho-ELISA positive samples (6 from each absorbance category) were also tested by Abbott ELISA and
(strongly reactive), RIBA:
ortho EL ISA + ve* Weak (6) Intermediate (6)
Abbott ELISA + ve 5 5 6
Strong
Chiron RIBA +
ve
0 1 6
*Cut-off value 0 451; +ve=positive.
16 samples were positive with the Abbott test and 7 with RIBA, 6 of which were strongly reactive with Ortho ELISA. The distribution
of absorbance values in Ortho ELISA was closely related to the distribution of anti-ENA ELISA vaues (r = 0-45; p =5x 10 - 6). Indeed, anti-ENA autoantibodies were found in 48 (81%) HCVpositive and 9 (26%) HCV-negative samples (Chi-square test
p< 10-6). Our
findings suggest
a relation between malaria and falseHCV results. The non-specific reacivity is probably attributable to antinuclear and other autoantibodies that arise in malaria patients.2 These can lead to false-positive reactions with HCV ELISA kits that are based on detection with an anti-IgG reagent, because of their high affinity for the solid phase.3We obtained closely similar results with Abbott and Ortho ELI SAs and found a close correlation between anti-ENA and anti-HCV optical density values. We showed false-positive tests only in intermediate and weakly reactive specimens. Our results therefore do not support Wong and colleagues’ suggestion that non-specificity can also arise in strongly reactive sera. Workers investigating HCV seroepidemiology in malarious regions should be aware of the possibility of false-positive reactions in order to establish a reliable profile of HCV antibody prevalence.
positive
This work was in part
supported by a grant from MURST, Project "Cirrosi
ed epatiti virali".
Institute for Tropical and Infectious Diseases, La Sapienza University, 00161 Rome, Italy
ANTONIO ACETI GLORIA TALIANI CARLO DE BAC ANTONIO SEBASTIANI
Manthorpe R, Bendixen G. Anti-ENA antibody in serum determined by ELISA-technique, description of method and recommended procedure. Allergy 1981; 36: 397-404. 2. Boonpucknavig S, Ekapanyakul. Autoantibodies in sera of Thai patients with Plasmodium falciparum infection. Clin Exp Immunol 1984; 58: 77-82. 3. Cafruny WA, Heruth DP, Jaqua MJ, Plagemann PGW. Immunoglobulins that bind to uncoated ELISA plate surfaces: appearance in mice during infection with lactate-dehydrogenase-elevating virus and in human anti-nuclear antibodypositive sera. J Med Virol 1986; 19: 175-86. 1. Struckmann J,
Cisapride and brittle asthma reflux disease (GORD) is fairly in chronic asthma1 and can be secondary to or aggravated by bronchodilator therapy. Oesophageal reflux contributes towards exacerbations of airflow obstruction in some asthmatics, though the mechanism is not clearControl of GORD in such patients can lead to substantial improvement in their asthma.3 Cisapride has been used successfully in the management of oesophageal reflux.1 As a prokinetic agent acting by the facilitation of cholinergic transmission in the myenteric plexus,s cisapride might affect other sites of cholinergic transmission, such as bronchial smooth muscle. We describe a chronic asthmatic whose asthma worsened after
SIR,-Gastro-oesophageal
common
cisapride. An
steroid-dependent asthma Her asthma was "brittle" with 20 hospital admissions in the preceding 12 months. Increased bronchial reactivity had been confirmed on bronchial challenge (PCj 0-09 mg/ml). Maintenance therapy included prednisolone 40 mg daily, inhaled salbutamol, inhaled beclamethasone 4000 fly daily, and oral theophylline (serum concentration 10-15 mg/1). Her asthma had been stabilised, with mean daily peak flow rates (PFR) of 4901/min (SD 23). She had confirmed disordered oesophageal motility and nocturnal pulmonary aspiration (radioisotope aspiration study), and ulcerative oesophagitis was found at 18-year-old
woman
with
severe
was admitted after an acute attack.
Peak flow rates before
(.) and after (*) cisapride.
gastroscopy. Antacids and an H2-receptor blocker were introduced, but symptoms of her reflux persisted and cisapride 10 mg thrice daily was introduced. Within 3 h of the first dose of cisapride, chest tightness and wheeze developed, and her PFR fell to 360 1/min. This pattern was also seen after the second dose. A total of four 10 mg doses were given before the drug was abandoned (figure). During the 48 hours of the cisapride trial the mean PFR was 435 1/min (42). On withdrawal of cisapride, PFR returned to baseline. It was considered unethical to rechallenge the patient once she had recovered. Asthma is not regarded as a contraindication for the use of cisapride.6 We believe that patients on cisapride with a history of asthma should be closely monitored. Although cisapride has been used in hospital patients with a history of respiratory disease,’ changes in expiratory flow rates have not been reported. The effect of cisapride on bronchial reactivity in healthy individuals and in asthmatics has not been described.
Sir Charles Gairdner Hospital, Nedlands, Perth, Western Australia
P. NOLAN M. PHILLIPS B. WILLIAMSON
1. Ekstrom T, Tibbling L.
Esophageal acid perfusion, airway function and symptoms in asthmatic patients with marked bronchial hyperactivity. Chest 1989; 96: 995-97. 2. Castell, DO. Asthma and gastroesophageal reflux. Chest 1989; 96: 2-3. 3. Perrin-Fayoue M. Long term results of surgical treatment for gastro-oesophageal reflux in asthmatic patients. Chest 1989; 96: 40-45. 4. Camilleri M, Malagehda J, Abell TL, Brown M, Hench V, Zinmeister A. Effect of six weeks of treatment with cisapride in gastroparesis and intestinal pseudoobstruction Gastroenterology 1989; 96: 704-12. 5. Tonini M, Galligan JJ, North RA. Effects of cisapride on cholinergic neurotesrismission and propulsive motility in the guinea pig ileum. Gastroenterology 1989; 96: 1257-64. 6. Drug Insert. Jansen-Cilag, 1990. 7. Malfroot A, Vandenplas Y, Verlinden M, Piepsz A, Dab I. Gastroesophageal reflux and unexplained chronic respiratory disease in infants and children. Pediatr Pulmonol 1987; 3: 208-13.
Low intraocular pressure in seasonal
affective disorder SIR,-Several psychophysiological abnormalities seem to be present in seasonal affective disorder (SAD).1 However, no exact biological basis for SAD is known. We have suggested a SADrelated lowering of ocular pressure.2.3 We have investigated intraocular pressure (IOP) in ten women with SAD (mean age 29 3 [SD 54]) and twelve female controls (27[4.8]). The women with SAD met DSM-III criteria for major depression, developing during the autumn or winter and improving in the spring, for at least two consecutive years. A score of 16 or more on the Hamilton rating scale for depression (HDRS) was required for entry to the study. The controls were hospital staff and none had had seasonal
depression. In both groups ocular examinations were normal, and most eyes emmetropic. All subjects gave written informed consent. IOP was measured four times 1 h apart, starting at 1600 h, with the were
1444
tonometer (Glaucon-Opticon). This time was chosen because winter depression is associated with a striking worsening of symptoms in the late afternoon, and because at this time IOP is stable in healthy subjects. All tonometric examinations were made during the late luteal phase of the menstrual cycle (days 20-25). The patients had higher HDRS scores in winter (February to December) than in summer (May to July) (20-7 [5’1] vs 2-6 [1’7]; p < 001). Patients had substantially lower mean (SEM) IOP values than controls in both seasons (winter 13 62 [0-43] vs 17 25 [051] mm Hg; summer 12 91 [0.39] vs 1485 [0.45] mm Hg; p < 001, Mann-Whitney U test). The difference in IOP values between women with SAD and the controls cannot be accounted for by non-specific factors such as age, time of day of ocular recordings, or phase of the menstrual cycle. Since the average IOP in the general population is higher in winter than in summer,4seasonal independence of abnormally low IOP values in a subgroup of winter depressives might be a trait characteristic of winter depression.
applanation
II Department of Psychiatry, School of Medicine in Gdansk, Gdansk-Wrzeszcz
ANDRZEJ STOJEK
Psychiatric Research Unit, 12 Wroclawska Street, 44-335 Jastrzebie-Zdroj, Poland
BOZENA KASPRZAK ANDRZEJ SLABIKOWSKI
1. Rosenthal
2.
NE, Sack DA, Gillin JCh, et al. Seasonal affective disorder. Arch Gen Psychiatry 1987; 41: 72-80. Stojek A, Bilikiewicz A. Bright artificial light lowers intraocular pressure and plasma sodium concentrations less in depressed patients than healthy controls. Plznen Lek Shorn 1988; 56: 157-60.
Stojek A, Kasprzak B, Bilikiewicz A. Changes in ocular humor dynamics in SAD patients after phototherapy. Paper presented at the 18th European conference on psychosomatic research. (August, 1990, Helsinki, Finland). 4. Blumenthal M, Blumenthal R, Peritz E, Best M. Seasonal variation in intraocular pressure. Am J Ophthalmol 1970; 69: 608-10. 3.
New drug
danger for children
SIR,-A worrying new drug danger to schoolchildren, first noted in the Netherlands and Switzerland, is starting to appear in the UK. Gifts of self-adhesive stickers, designed to be stuck on the skin as decoration, are being offered to children of all ages. After a warning from British Army headquarters in Germany, and since many service families live in the area, a Portsmouth primary school sent out a circular giving details of four drug-impregnated decorative stickers brought back to and circulated in the UK. A 15-year-old boy with adolescent behaviour difficulties attended an "acid house" party on the Isle of Wight. There was a suspicion that illegal drugs had been passed at the party, and he admitted that several types of drug-impregnated decorative stickers had been seen there and that in a few instances these had been attached to the entrance tickets. He did not admit to having or handling any of these stickers, and did not appear to have any
drug-related problems. So far the sitckers found are: (1) a blue star on white background, (2) a small token named "Window Pane" with motifs to cut out, and (3) a small card with the name "Rote Pyramide" (red pyramid) printed on it. Also there have been tiny coloured grains/seeds intended to be swallowed. The stickers are impregnated with LSD (lysergide), strychnine, and, possibly, a phenothiazine, some of which is absorbed through the skin even when the stickers are held in the hand. They may cause rapid and unpredictable reactions; a few children may get headaches, vomiting, hallucinations, and or fluctuating temperature. The aim is to cause dependency and therefore new customers for Europe’s illegal drug trade. The smaller the child the greater the relative dose absorbed and the greater the risk of symptoms. Symptoms are far more likely if the stickers are licked, as is sometimes advised. Sometimes the stickers are attached to tickets for acid house parties, which may be attended by children as young as 10 years who, in all innocence, go for the music. Parents, teachers, and doctors have a responsibility to identify and, as far as possible, to prevent these risks by publicity leading to greater awareness of the problem. Paediatric Department, St
Mary’s Hospital, Newport, Isle of Wight, PO30 5TG, UK
E. S. MUCKLOW
Digital clubbing SIR,-We wish to comment on your Oct 6 editorial on clubbing. We have studied clubbing in cyanotic heart disease, an entity in which the acropachy is constant and usually life-long,’ and in primary hypertrophic osteoarthropathy (HOA), in which the syndrome is not accompanied by any underlying illness.2 We agree that assessment of finger clubbing should be uniform so that groups of patients and/or responses to therapy can be compared; therefore, we have proposed the "digital index"3 as a simple measure of clubbing. It is reproducible and clearly distinguishes clubbing from the normal finger shape. While we agree that our fmdings with respect to bony changes in clubbed digits’ have not been confirmed by others, to our knowledge no one else has studied this systematically. The vascular changes of clubbing are not limited to vasodilatation: apart from excessive fibroblast proliferation, there is also structural vessel damage. Electronmicroscopic studies have shown endothelial cell injury.5 Our studies on pathogenesis showed normal circulating concentrations of growth hormone in both groups of patientsIn HOA, inflammatory and autoimmune changes are not found by conventional serology; therefore we proposed that a fibroblast growth factor could be responsible for the syndrome.6 This growth factor would normally be present in the central venous circulation and removed in the lung. Subsequently, Dickinson and Martin7 suggested that this growth factor could be platelet-derived. Their theory was based on a mathematical model proposed by Trowbridge et al,8 which suggested that in normal circumstances large platelets are fragmented in the lung. In patients with cardiogenic HOA we have found a bizarre platelet population with features that agree with the Trowbridge model 9 Thus, these data suggest that localised activation of platelet-endothelial cells, with the ensuing release of growth factor(s), is a key feature in the development of clubbing. The First International Workshop on HOA will be held in Dubrovnik, Yugoslavia, in September, 1991. It is hoped that this meeting will help to settle some of the controversies described here. Instituto Nacional de
Cardiologia
MANUEL MARTÍNEZ-LAVÍN CARLOS PINEDA
Ignacio Chávez, 14080 México D.F Mexico
M, Bobadilla M, Casanova JM, Attié F, Martinez M. Hypertrophic osteoarthropathy m cyanotic congenital heart disease; its prevalence and relationship to bypass of the lung. Arthritis Rheum 1982; 25: 1186-93. Martinez-Lavin M, Pineda C, Valdez T, et al. Primary hypertrophic
1. Martinez-Levin
2.
osteoarthropathy. Semin Arthritis Rheum 1988; 17: 156-62. Vazquez-Abad D, Pineda C, Martinez-Lavin M. Digital clubbing; a numerical assessment of the deformity. J Rheumatol 1989; 16: 518-20. 4. Pineda C, Fonseca C, Martinez-Lavin M. Radiologic vignette: the spectrum of soft tissue and skeletal abnormalities of hypertrophic osteoarthropathy. J Rheumatol 3.
1990; 17: 626-32. M, Cinti S, Morroni M,
et al. Pachydermoperiostosis (primary hypertrophic osteoarthropathy): report of a case with evidence of endothelial and
5. Matucci-Cerinic
connective involvement. Ann Rheum Dis 1989; 48: 240-46. 6. Martinez-Lavin M. Digital clubbing and hypertrophic osteoarthropathy: a unifying hypothesis. J Rheumatol 1987; 14: 6-8. 7. Dickinson CJ, Martin JF Megakaryocytes and platelet clumps as the cause of finger dubbing. Lancet 1987; ii. 1434-35. 8. Trowbridge EA, Martin JF, Slater DN. Evidence for a theory of physical fragmentation of megakaryocytes, impying that all platelets are produced in the pulmonary circulation. Thromb Res 1982; 28: 461-75. 9. Vazquez-Abad D, Martinez-Lavin M. Macrothrombocytes in the peripheral circulation of patients with cardiogenic hypertrophic osteoarthropathy. Clin Exp Rheumatol (in press).
Monocyte activation and increased procoagulant activity in unstable angina SIR,-Increased A
thrombin
formation
revealed
plasma concentrations (FPA) is
by raised
in unstable angina. 1-3 The causes and mechanisms of the enhanced thrombin formation are unknown. Since monocyte/macrophages are a characteristic component of the coronary atherosclerotic plaque in such patients,4-6 we investigated the role of monocytes in increased thrombin formation. We studied 28 patients with unstable angina, 18 with stable effort angina, and 30 controls matched for age. Patients with unstable angina had higher FPA plasma concentrations (mean 7-67 [0-59]
fibrinopeptide
common
