764
they suggested that because nifedipine produces little venodilatation, first-dose hypotension should not arise with this agent. Nifedipine has become established as an important agent in all grades of hypertension. However, we would like to remind our colleagues that it, like other antihypertensive drugs, can cause unpredictable and severe hypotension. We are unaware of other reports implicating in this effect the tablet form of this drug rather than the capsule, and it should be noted that the retard form of indeed
nifedipine is not strictly slow release although its onset of action is more gradual that that of the capsule.4 We believe that there are no ideal agents for the management of hypertension and that treatment should begin with drugs in low dose with strict bed-rest and careful blood pressure monitoring in hospital, avoiding rapid reductions except in a few real severe
emergencies. Cardiology Department, Royal Hallamshire Hospital, Sheffield S10 2JF, UK
P. WOODMANSEY K. S. CHANNER
1. Wachter RM. Symptomatic hypotension induced by nifedipine in the acute treatment of severe hypertension. Arch Intern Med 1987; 147: 556-58. 2. O’Mailia JJ, Sander GE, Giles TD. Nifedipine associated myocardial ischaemia or infarction in the treatment of hypertensive urgencies. Ann Intern Med 1987; 107: 185-86. 3. Leavitt AD, Zweifler AJ. Nifedipine, hypotension, and myocardial injury. Ann Intern Med 1988; 108: 305. 4. Pasanisi F, Meredith PA, Reid JL. Pharmacokinetics of nifedipine. Int J Clin Pharm Res 1985; 5: 63-66. 5. Raemsch KD, Sommer J. Pharmokinetics and metabolism of nifedipine. Hypertension 1983; 5 (suppl II): 18-24. 6. Taburet AM, Singlas E, Colin J, Banzet O, Thibonnier M, Corvol P. Pharmacokinetic studies of nifedipine tablet. Hypertension 1983; 5 (suppl II): 29-33. 7. Capewell C, Capewell A. "First dose" hypotension and venodilation. Br J Clin Pharmacol 1991; 31: 213-14.
Narrowing inequalities
in children’s
height
SiR,—There is substantial evidence that over the past decades differences between socioeconomic groups in adult mortality rates have increased in many industrialised countries.1-3 Although this suggests that the welfare state has not been as successful at reducing health inequalities as was hoped originally, it is important not to jump to conclusions before more health indicators have been
investigated. Data on inequalities in children’s height provide an opportunity for studying another aspect of health. Although body height attained at different ages is dependent on genetic factors, conditions during childhood relevant to health, such as nutrition and disease, determine whether the individual realises full growth potential. Differences in children’s height between socioeconomic groups as indirect measures for health status difference. In the Netherlands there has been a tradition of monitoring children’s height that goes back to the 19th century.’ Although a
may therefore be used
SOCIOECONOMIC DIFFERENCES IN HEIGHT OF CHILDREN IN NETHERLANDS, 1964-66 AND 1980
NA, not available *Children classified according to occupational status of father In each study, 3 categories were distinguished high, middle, and low High category contained about 5% of children in 1964-66, and about 8% in 1980 Low category contained about 60% of children m 1964-66, and about 50% m 1980 tNatlonwlde, representative sample of about 55 000 children, differences calculated from data in ref 4 tNat!onwde, representative sample of about 42 000 children, differences calculated from data m ref 7
formal comparison between the results of these early studies and present fmdings is difficult, because of variations in sampling and socioeconomic classification, differences have become much smaller. Differences of 5-10 cm at various ages between children whose father had a low versus a high occupational status were common in the 19th and early 20th centuries,6 whereas differences now are about 1-3 em.4,7 A comparison of the results of two surveys (1964-66 and 1980) shows that the reduction of inequalities in children’s height continued up to 1980 (table). Both surveys were of large representative samples of Dutch children and used the same socioeconomic classification based on the occupational status of the child’s father.4,7Although the 1980 survey still showed differences in average body height between children in high and low socioeconomic groups, these were inconsistent at younger ages, and substantially smaller than those in the 1964-66 survey. Although similar findings have been reported for some other countries,8,9 the relevance of such data to the debate on health inequalities has not been fully recognised until now. These reports suggest that in a period with increasing adult mortality differentials, inequalities in children’s health status may have been decreasing, and that the development over time of inequalities in health does not present a consistently gloomy picture. Department of
Public Health and Social Medicine, Erasmus University, 3000 DR Rotterdam, Netherlands
J. P. MACKENBACH
1. Marmot MG, McDowell ME. Mortality decline and widening social inequalities Lancet 1986; ii: 274-76. 2. Vågero D. Klass och dodlighet. In: Diderichsen F, et al, eds. Klass och halsa. Stockholm: Tidens forlag, 1991. 3. Kunst AE, Looman CWN, Mackenbach JP. Socio-economic mortality differences in the Netherlands in 1950-84: a regional study of cause-specific mortality. Soc Sci Med 1990; 31: 141-52. 4. van Wieringen JC. Seculaire groeiverschuiving. Leiden: Nederlands Institut voor Praeventieve Geneeskunde TNO, 1972. 5. Coronel S. De ligchamelijke ontwikkeling in verband tot den maatschappelijke toestand en den arbeid der kinderen. Schat der Gezondheid 1862; 5: 193-215. 6. Moquette JJR. Onderzoekingen over volksvoeding in de gemeente Utrecht. Utrecht. University Thesis, 1907. 7. Roede MJ, van Wieringen JC. Growth diagrams 1980; Netherlands third nation-wide survey. Tijdschr Soc Gezondheidsz 1985; 63 (suppl): 1-23. 8. Nystrom Peck M, Vagero DH. Adult body height and childhood socio-economic group in the Swedish population. J Epidemiol Comm Health 1987; 41: 333-37. 9. Teasdale TW, Sørensen TIA, Owen DR. Fall in association of height with intelligence and educational level. Br Med J 1989; 298: 1292-93.
Calcipotriol and hypercalcaemia SiR,—The vitamin D analogue calcipotriol has been introduced for the treatment of psoriasis. Because of low absorption and rapid degradation it is said to have little effect on serum calcium.’ We report a patient with severe symptomatic hypercalcaemia after treatment with topical calcipotriol (’Dovonex’). A 67-year-old woman with exfoliative psoriasis covering 40% of her body was prescribed the ointment (calcipotriol 50 flg/g) to be used twice daily. We estimate that over a week she applied 200 g. After 7 days of treatment she became unwell with nausea, muscle weakness, and abdominal pain. Her serum calcium was 351 mmol/1 (corrected to an albumin of 44 g/1); the normal range is 2-2-26 mmol/l. The calcipotriol was stopped and a high fluid intake maintained. Her serum calcium soon fell and eventually returned to normal:
The patient had a moderate degree of renal impairment but was other relevant medication. Her serum calcium 2 weeks before the calcipotriol treatment had been normal, as were previous estimations over 4 years. on no
765
The patient had exceeded the recommended maximum dose of 100 g weekly and had applied the treatment to extensive unstable psoriasis. According to the manufacturer’s data sheet (Leo Laboratories) calcipotriol is known to cause increased serum calcium if applied in daily doses of 50-100 g of the 50 )ig/g ointment. Bower et al2 reported that application of the ointment under occlusion produced hypercalcaemia in two patients. The irritated condition of the skin and an occlusive effect from added emollient may have contributed to increased absorption in our patient. Calcipotriol is now being recommended for localised plaque psoriasis.’ Our experience with this patient indicates that its use on extensive unstable disease is potentially hazardous. We recommend adherence to the manufacturer’s recommended maximum dose of 100 g per week and its use on cases of stable mild-to-moderate
psoriasis. Department of Dermatology Stobhill General Hospital, Glasgow G21 3UW, UK
COLM DWYER R. S. CHAPMAN
Kragballe K, Gjertsen BT, de Hoop D, et al. Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris. Lancet 1991; 337: 193-95. 2. Bower M, Colston KW, Stein RC, et al. Tropical calcipotriol treatment of advanced 1.
g/1 or less obtained from women with increased scalp hair shedding is not at variance with this hypothesis, nor is it a cut-off point for all individuals. In fact, subject 2 in our study conceived with a serum ferritin concentration of 36 ug/1; however, she still had excessive hair shedding. Worwood cites Cook et al2, but that study makes no comparisons
40
between stainable iron in the bone marrow and the indices used to assess iron sufficiency. Additionally, a disproportionately high number of individuals were anaemic, none of whom were excluded from their homogeneous subsets. One could postulate therefore that their median serum ferritin value of 27 ug/1 suggests that 50% of the US female population less than 45 years old may have ferritinrelated fertility problems. We feel that it is noteworthy that the post-menopausal median value was 63 ig/1. If fertility is affected by depleted iron stores, and our data suggest that it is, the only point of contention is the range over which serum ferritin concentrations indicate this association. We believe that the lower reference value of 15 ug/1 generally cited for premenopausal women is too low, and that the male or post-menopausal female range offers a much more reliable guide to iron depletion. Clearly, further work is required to resolve this and other issues raised by our
findings.
breast cancer. Lancet 1991; 337: 701-02.
Ferritin and
fertility
SIR,-Dr Rushton and colleagues (June 22, p 1554) propose that "conception is prevented in women with depleted iron stores, as assessed by serum ferritin values". If it is correct, this observation is very important since it suggests that efforts to eradicate iron deficiency anaeniial
may accelerate further the increase in world
population. Their indication
for depleted iron stores is a serum ferritin concentration of less than 40 p.g/1. This cut-off point was established by comparison with a range of 40-165 pg/1 in 10 healthy controlsZ However, the supposition that women with a serum ferritin concentration of less than 40 )ig/l have depleted iron stores is incorrect. In healthy people, serum ferritin concentration is generally accepted to indicate the level of iron stores. Mean concentrations are higher in men than in women and values of less than 15 g/1 are associated with the absence of storage iron.3 The most comprehensive population surveys have been done in North America, and in women under 45 years the median serum ferritin concentration is about 25 )g/l. This value corresponds to about 300 mg of storage iron.4 There is thus no evidence to support Rushton and colleagues’ statement that serum ferritin concentrations of less than 40 (ig/1 indicate storage iron levels that can be regarded as depleted, at least with respect to young women. Department of Haematology, University of Wales College of Medicine,
MARK WORWOOD
Heath Park, Cardiff CF4 4XN, UK 1.
Report of an IAEA, USAID, WHO joint meeting. Control of nutritional anaemia with special reference to iron deficiency. Geneva: World Health Organisation: Tech Rep
Ser 580, 1975. 2.Rushton DH, Ramsay ID, James KC, Norris MJ, Gilkes JJ. Biochemical and trichological characterization of diffuse alopecia in women. Br J Dermatol 1990; 123: 187-97. 3. Worwood M. Serum ferritin. In Jacobs A, Worwood M, eds. Iron in biochemistry and medicine, II. London: Academic Press, 1980: 203-44. 4. Cook JD, Skikne BS, Lynch SR, Reusser ME. Estimates of iron sufficiency in the US
population. Blood 1986; 68: 726-32.
**This letter has been shown whose reply follows. -ED. L.
to
Dr Rushton and his
colleagues,
SIR,-We agree with Dr Worwood that our findings could have important consequences for some women with fertility difficulties. However, the point of our report was that depleted iron stores may be associated with fertility difficulties. Worwood ignores data from young
healthy
women
in whom
serum
ferritin concentrations
as
high as 52 g/1 have been associated with an absence of stainable iron in the bone marrow.1 From this and Worwood’s data it seems that depleted iron stores are estimated by a range of serum ferritin concentrations. Contrary to his suggestion, our proposed cut-off of
School of Pharmacy and Biomedical Sciences, Portsmouth Polytechnic, Portsmouth PO1 2DZ, UK
D. H. RUSHTON I. D. RAMSAY J. J. H. GILKES M. J. NORRIS
J. Serum ferritin in the evaluation of iron status m young healthy women. Acta Obstet Gynecol Scand 1980; 95 (suppl): 35-41 2 Cook JD, Skikne BS, Lynch SR, Reusser ME. Estimates of iron sufficiency in the US population. Blood 1986; 68: 726-31. 1. Puolakka
Role of thrombelastography in bleeding diatheses and regional anaesthesia SIR,-Dr Cross and colleagues (July 20, p 187) rightly point out the dilemma that increasingly faces anaesthetists when assessing the risk/benefit ratio of major regional anaesthesia in patients with potential bleeding diatheses due to pre-eclampsia, or to anticoagulant therapy with aspirin or subcutaneous heparin. The possibility of an epidural haematoma, in the absence of an adequate test to identify coagulation derangement, can lead to patients being denied epidural anaesthesia.1 They query the potential role of thrombelastography as a predictor of bleeding in patients on aspirin. The thrombelastograph (manufactured by Haemoscope and PPG, Hellige) fulfils many of the criteria for a sensitive, specific, and rapid way to assess coagulation in these patients. It enables a wide assessment of haemostatic function to be made from one blood sample, documenting the process of clot initiation as well as the structural characteristics of the formed clot and its stability.2 The tracings provide information on clotting factor activity, platelet function, and any clinically significant fibrinolytic process within 20-30 min. Thrombelastography (TEG) is a far more sensitive indicator of the response to heparin than activated partial thromboplastin time.3 Heparin affects several TEG indices, especially reaction time (r) (the time from blood sampling until the clot begins to form). This value represents intrinsic clotting and is very sensitive to thromboplastin procoagulants. The maximum amplitude (ma) achieved by the TEG tracing indicates the strength of the fibrin clot and is a direct function of the maximum dynamic properties of fibrin and platelets. Platelet abnormalities substantially disturb this index. In patients with pre-eclampsia epidural anaesthesia is often beneficial. However, coagulopathy may develop rapidly as the disease progresses, with decreased platelet count, abnormal platelet function, and increased platelet consumption.4 TEG is more useful than standard coagulation tests for evaluating coagulopathies in such patients.s Since functional quality rather than number of platelets is important, thrombocytopenia (< 100 000/ul) in the presence of a normal ma would not be a contraindication for regional anaesthesia. A reduced ma, even with an acceptable platelet count, alerts the anaesthetist to the increased risk of complications with epidural anaesthesia. Other than the use of template bleeding time, which has its