EVALUATION OF TEST KITS FOR GONADOTROPINS

616

tightness and pain in chest followed with tingling in lower arms, agitation and restlessness, then soreness in lower back". He gradually recovered. A 21-year-old woman (on oral contraception) took two 60 mg tablets in 1 day and experienced euphoria, giddiness, in a "high"; she started giggling at anything and had to be home from work. To our knowledge this is the first series of adverse non-sedating CNS symptoms to be reported after the first doses of terfenadine in adults. If there is a causal relation, the patients are probably hypersusceptible and the incidence is probably very low. The symptoms resemble those reported with the older, sedating antihistamines.1,2 Terfenadine is thought not to cross the bloodbrain barrier readily in therapeutic dosage,2.3 but even if only half the cases presented were causally related some drug penetration of the brain must have occurred.4 The male/female ratio of 1 to 4 in this small series is interesting but needs confirmation. sent

Department of Pharmacology, University of Montreal, Montreal, Quebec H3C 3J7, Canada; and Product Related Disease Division,

EDWARD NAPKE PIERRE BIRON

Health Protection Branch, Health and Welfare, Ottawa

Postgrad Med 1986; 79: 75-86. 2. Brandon ML. New non-sedating antihistamines: will they replace older agents? Drugs 1985; 30: 377-81. 3. Lunde I. Antihistamines. In: Dukes MNG, ed. Side effects of drugs annual 10. Amsterdam: Elsevier, 1986: 135-36. 4. Adverse Drug Reactions Advisory Committee. Terfenadine. Australian Adverse Drug Reactions Bull 1987 (Nov). 1. Schuller DE, Turkewitz D. Adverse effects of antihistamines.

PERCUTANEOUS EXCIMER LASER CORONARY ANGIOPLASTY

SIR,-Initial attempts at percutaneous laser assisted coronary angioplasty (PTCA) with an argon laser-heated metal probe were limited by the difficulties of manoeuvering the device through tortuous coronary lesions1 and by thermally induced thrombosis.2 It has been suggested that pulsed excimer laser irradiation, which vaporises fibrocalcific lesions and causes less thermal damage to underlying neointima, may be safer and more effective than thermal laser angioplasty systems. Dr Litvack and colleagues (July 8, p 103) report the use of excimer PTCA. Our experience is as follows. A 66-year-old man with a 1-year history of progressive angina and a positive stress test on treatment underwent conventional PTCA of an 80% proximal left anterior descending stenosis that could only be reduced to 30% residual stenosis because of the eccentricity of the lesion (fig A, B). The patient was pain-free for two months but then symptoms recurred. Repeat angiography confirmed restenosis (fig C) and excimer laser assisted balloon angioplasty was done in an attempt to achieve a better result by partly vaporising the lesion. A xenon chloride (308 nm) pulsed excimer laser generator (CVX-300, Spectranetics, Colorado

Excimer laser assisted coronary

angioplasty.

A, 80% eccentric proximal LAD stenosis before initial PTCA; B, 30% residual stenosis after PTCA with a 3-5 mm balloon catheter; C, restenosis lesion; D, fmal angiographic result with no residual stenosis after excimer laser assisted angioplasty.

Springs, USA) and a 4-5 F central lumen catheter consisting of 13 concentrically arranged 200 Nun optic fibres were used to recanalise the lesion and reduce the stenosis to 50% (30 mj/mm, 25-35 Hz, 949 pulses). Subsequent balloon angioplasty with the same size balloon catheter used in the earlier attempt (35 mm) resulted in no residual stenosis (fig D). The patient was discharged and remains symptom-free three months post procedure. Overall, the feasibility of this percutaneous coronary excimer laser angioplasty system as an adjunct to PTCA has been assessed in 23 patients. In contrast to some coronary experience with laser probe devices,l-4 there was no acute spasm, thrombosis, or perforation associated with the pulsed excimer laser procedure in these patients. In this patient a pulsed excimer laser and a percutaneous coronary delivery system have been successful in providing a better angiographic result than an earlier attempt with the same size balloon catheter. Although these initial results are encouraging, confirmation that any laser system improves the treatment of coronary artery disease awaits six months angiographic follow-up in randomised trials.

Division of Cardiology, Department of Medicine, Mount Sinai Medical Center, New York, NY 10029, USA; and The New York Cardiac Center

TIMOTHY A. SANBORN RONNIE A. HERSHMAN SABINO R. TORRE WARREN SHERMAN MARC COHEN JOHN A. AMBROSE

1. Sanbom TA, Faxon DR, Kellett MA,

Ryan TJ. Percutaneous coronary laser thermal angioplasty. J Am Coil Cardiol 1986; 8: 1437-40. 2. Cumberland DC, Starkey IR, Oakley GDG, et al. Percutaneous laser-assisted coronary angioplasty. Lancet 1986; ii: 214. 3. Sanbom TA, Bonan R, Cumberlandf DC, et al. Percutaneous coronary laser-assisted balloon angioplasty with flexible central lumen laser probe catheters. Circulation 1988; 78 (suppl II): 295 (abstr). 4. Linnemeier TJ, Bonan R, Cumberland DC, et al. Human percutaneous laser-assisted coronary angioplasty of saphenous vein bypass grafts: early multicenter experience. Circulation 1988; 78 (suppl II): 295 (abstr).

EVALUATION OF TEST KITS FOR GONADOTROPINS

SIR,-We have evaluated seven commercial kits for the of luteinising hormone (LH)l and follicle stimulating hormone (FSH)z in serum. We found, as already shown in the national external quality assessment scheme, that the immunometric assays with monoclonal antibodies give considerably lower values for LH concentration in serum specimens than the radioimmunoassays with polyclonal antibodies. This difference is partly a result of the greater specificity of the measurement

monoclonal antibodies which do not measure subunits of LH and FSH and, more importantly, the measurement of particular epitopes of the glycoproteins in serum. The various monoclonal antibodies measure different epitopes. We found that the concentration of LH varied between patients’ samples with different kits (figure). Although some kits (IDS, Medgenix, NETRIA, and Serono) show a relation in LH concentration between specimens similar to the Baxter kit, the Behring and LKB (Pharmacia) kits do not. The Behring kit measured LH concentration for specimen 7 more than five-fold higher than the other specimens. The Serono kit also gave a much higher concentration for specimen 7; but it also showed this in specimen 8. It seems that the monoclonal antibodies used in these kits recognised an epitope of LH with a high concentration in specimens 7 and 8, not recognised by the other kits. These differences cannot be explained by assay imprecision since these 7 kits have a high performance, with a within-assay error of less than 5%. These differences will have a considerable effect on reference ranges and could make interpretation of patients’ results difficult. The differences between kits for LH were not shown for FSH. In fact, the levels of FSH measured by immunometric assay are not greatly different from those measured by radioimmunassay. Therefore, the ratio of LH to FSH in a specimen depends on the assay technique used and will be much lower when immunometric assays are used. The rule that a characteristic of the polycystic

617 expect the response to pamidronate in patients with hypercalcaemia due to breast cancer to be much better than the 47% success in their series of 15 patients with malignancies of various origins. We have studied the response to intravenous pamidronate in 25 patients with breast cancer and symptomatic hypercalcaemia (duration of follow-up at least 14 days). In 23 patients thirty-four episodes of hypercalcaemia could be easily controlled with rehydration followed by pamidronate. Serum calcium returned to normal in 6 days on average (SEM 1 day); pamidronate was administered for 6 (0-5) days and the total dose was 75 (9) mg. In these patients the serum phosphate concentration immediately before each course of pamidronate was normal or above normal. In 1 patient the serum calcium did not return to normal despite three courses of pamidronate. The serum phosphate was lownormal before the first course (0 84 mmol/1) and clearly subnormal before the last two (073 and 0 59 mmol/1). The other patient responded twice to pamidronate but resistance developed when serum phosphate concentrations became subnormal (060 mmol/1). Our data are in accord with the conclusion of Gurney et al that in patients with hypercalcaemia of malignancy and pseudohyperparathyroidism pamidronate is less effective. Furthermore, our fmdings confirm that mammary carcinoma rarely produces a PTH-like factor. Division of Endocrinology, Department of Medicine, St Radboud Hospital,

L. BEEX A. HERMUS A. SMALS

University of Nijmegen, 6500 HB Nijmegen, Netherlands

1. Stewart A, Horst R, Deftos L, et al. Biochemical evaluation of patients with cancer-associated hypercalcemia: evidence for humoral and nonhumoral groups. N

Engl J Med 1980; 303: 1377.

LH serum concentrations in 11 prepubertal children, measured seven

by

commercial kits.

Baxter Healthcare radioimmunoassay kit which gives consistently higher results than other kits, used as reference. LH concentrations, joined for ease of interpretation.

ovarian syndrome is an LH/FSH ratio greater than 3 is now clearly wrong when immunometric assays are used. We advocate that its use should now be dropped from scientific investigations of this

syndrome. Department of Health Evaluation Unit, Department of Chemical Pathology, St Thomas’ Hospital,

SiR,—The interesting observations of Dr Gurney and his colleagues prompted us to review the relation between renal tubular phosphate threshold and calcium-lowering response in 55 patients treated with intravenous pamidronate over the past 4 years. The doses ranged from repeated daily infusions of 15 mg for 3-10 days1 to single infusions of 5-45 mg.2 Allocation to treatment was randomised; in Gurney’s series patients with the most severe hypercalcaemia got the highest doses. Methods used were as described/,2 the notional renal tubular threshold for calcium reabsorption (TmCa/GFR) was calculated with the computer program that Gurney et al used (Rorer Pharmaceuticals). The

nadir

of

serum

calcium

post-treatment correlated with the following

significantly (Spearman’s rank correlation) M. J. WHEELER

London SE1 7EH

AGNES D’SOUZA

NHS Procurement Directorate, Department of Health, London WC1

A. N. HORN

biochemical variables pre-treatment: serum inorganic phosphate (r = - 0-43, p< 0-001), serum calcium (r=0’37, p < 0-006), and renal tubular phosphate threshold (TmP/GFR) (r = - 0-35, p < 0-009). There was a positive correlation between TmCa/GFR and the nadir of serum calcium (r = 0-25), but this was not significant. In the subgroup of patients treated with repeated infusions of pamidronate (n = 11) the correlation between TmCa/ GFR and nadir of serum calcium values was significant (r 0-62, =

1. D’Souza A, Wheeler MJ, Horn AN. An evaluation of commercial kits for the measurement of serum and plasma LH (part II). London: Department of Health 1989:

STD/89/05.

2. D’Souza A, Wheeler MJ, Horn AN. An evaluation of commercial kits for the measurement of serum and plasma FSH (part II) London: Department of Health

p

<

0’04).3 CLINICAL AND BIOCHEMICAL VARIABLES IN GOOD AND POOR

RESPONDERS*

TO INTRAVENOUS PAMIDRONATE

(in press).

PAMIDRONATE AND HYPERCALCAEMIA OF MALIGNANCY

SIR,-Dr Gurney and colleagues (July 29, p 241) suggest that the response to pamidronate (aminopropylidene diphosphonate, APD) in hypercalcaemia of malignancy is less favourable in patients demonstrating changes associated with the action of a parathyroid hormone (PTH)-like factor. In their study a low renal phosphate threshold was the best single indicator of failure of response to pamidronate. In advanced breast cancer, with possible rare exceptions, is thought to result from osteolysis by bone metastases, and not from production of a PTH-like factor by tumour tissue.’ If Gurney’s hypothesis were correct one might

hypercalcaemia

Values are medians (range). *Serum (albumin-adjusted) calcium greater than 2-65

mmol/1.