Bisphosphonate-induced bronchoconstriction in aspirin-sensitive asthma

being evaluated in controlled trials (such as aspirin therapy and calcium supplements) are not discussed. The unreferenced statement that "the higher incidence of pre-eclampsia in women of low socioeconomic groups has been related to lower protein intake", is unhelpful. Historically, both low and high protein diets have been vociferously. advocated in the prevention and treatment of pre-eclampsia, a debate that Arbogast and colleagues seem determined to resurrect, oblivious to the lack of evidence from either

observational epidemiological studies or randomised controlled trials of a link between protein intake and preeclampsia.2 Furthermore, there is no consistent evidence that the incidence of pre-eclampsia is higher in lower socioeconomic groups.3 Pre-eclampsia is essentially a disorder of implantation that is

nulliparous women and is associated with reduced placental perfusion and generalised endothelial dysfunction, secondary to the condition.4 There is evidence that pre-eclampsia is modified by environmental factors. For instance, it is commoner in the obese, in women with hypertension, and in non-smokers.3 Arbogast’s hypothesis would be more persuasive if it accommodated observations such as these and in particular the intriguing inverse association between cigarette smoking and the risk of preeclampsia.

commoner

bisphosphonates are likely to become in the prophylaxis and treatment of corticosteroid-associated osteoporosis, whether the effect observed by Rolla et al represents an idiosyncratic response or a major therapeutic side-effect needs to be established. is not clear. Since

important agents

Stephen J Gallacher, Kenneth Anderson, Stephen W Banham, lain T Boyle University Department of Medicine and Respiratory Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK

Tashjian AH. Prostaglandins, hypercalcaemia and cancer. N Engl J Med 1975; 293: 1317-18. Gallacher SJ, Fraser WD, Cruickshank AM, Shenkin A, Boyle IT. The response of plasma interleukin-6 (IL-6) to pamidronate. Bone 1990; 11: 384.

1 2

in

Mohs surgery SIR—The Mohs technique for the evaluation of excision of skin

lesions, the subject of Dzubow’s commentary (Feb 19, p 433), has much to commend it. There are, however, some practical

drawbacks, the main one being that since the skin specimen has to be processed for cryotomy in its entirety little or no representative tumour tissue may remain for paraffin section examination. This can sometimes make it difficult to arrive at a definitive microscopic diagnosis. Also the cutting of the multiple cryotome blocks required is time-consuming and

Ivan J Perry Department of Public Health, Royal Free Hospital School of Medicine, London NW3 2PF, UK

expensive. 1 2

3 4

Weed DL. On the logic of causal inference.

Am J Epidemiol 1986;

123:

965-79. Brown MA. Non-pharmacological management of pregnancy-induced hypertension. J Hypertens 1990; 8: 295-301. Eskenzi B, Fenster L, Sidney S. A multivariate analysis of risk factors for preeclampsia. JAMA 1991; 266: 237-41. Pre-eclampsia: more than pregnancy-induced hypertension. Lancet 1993; 341: 1447-51.

Bisphosphonate-induced bronchoconstriction in aspirin-sensitive asthma SiR-Rolla and colleagues (Feb 12, p 426) describe two patients who had exacerbation of asthma associated with the use of intravenous clodronate and oral etidronate. We have treated a total of 83 patients with corticosteroid-dependent asthma or chronic obstructive airways disease with three different bisphosphonates and have not recorded this reaction. 27 patients received intravenous pamidronate at a dose of 30 mg once every three months, 21 patients oral clodronate at a dose of 800 mg per day for three months out of every six, and 35 patients oral etidronate (Didronel PMO). All patients treated with intravenous pamidronate received their first infusions as inpatients to observe side-effects, including changes in peak expiratory flow rate (PEFR). No problems were encountered other than the development of a transient self-limiting fever in about 30% of patients. PEFR was not formally recorded before and after bisphosphonate therapy in patients treated with oral or etidronate; however, no patient reported significant deterioration in their asthma over this time.

clodronate

Rolla

et

any

al suggest that the bronchoconstriction in their

patients might be due to alterations in prostaglandin activity. Although there is some evidence that prostaglandin E2 is associated with increased bone resorption, this effect is likely to be small as treatment with prostaglandin synthase inhibitors do not substantially suppress bone resorption.1 The use of intravenous bisphosphonates has been shown to be associated with cytokine release (particularly interleukin-6)though whether this might have a role in inducing bronchoconstriction 924

There are alternative methods, which allow full margin evaluation on paraffin sections but without the need for extensive cryotomy since the whole specimen can also be submitted for paraffin processing (figure). The normal skin at the periphery of the ellipse of skin surrounding the lesion can be marked with the tip of a scalpel dipped in indian-ink or equivalent dye and the tip of the scalpel is then run around half of the perimeter of the biopsy area.1 Transverse and cruciate blocks of the lesion are taken, as required, and the whole specimen may be blocked out for histology. With microwave fixation techniques, skin specimens can now be definitively evaluated with "routine" histological techniques, without the Mohs technique, in less than 12 hours from the receipt of the skin specimen in the laboratory. Perhaps Mohs technique should be reserved for those situations where the adequacy of excision of a skin lesion is in doubt and where a second procedure (ie, re-excision) is undesirable, rather than as a primary form of management and pathological margin

Figure: Excision margin marking, permitting subsequent whole specimen histology Broken tines = orientation sutures; inked with scalpel tip.

arrow=

margin