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patches.’ In sheep, progesterone reverses the increase in uterineblood flow seen after oestradiol administration, and a similar effectmay be expected with potent synthetic progestagens such as

norethisterone. Norethisterone has a half-life of up to 12 h, hence acarry-over effect has to be considered. The stage in the treatment

cycle at the time of observation may be critically important. Theresolution of currently available ultrasound equipment does notallow accurate measurement of endometrium less than 1 mm thick;thus, the data presented cannot serve as a measure of compliancewith treatment.

Oestradiol may act via a genomic or classic oestrogen receptormechanism to bring about changes in vessel wall distensibility byprotein synthesis. These would be reflected in the PI, as

demonstrated by Bourne et al. However, oestradiol is known to actas a vasodilator by mechanisms independent of the cytosol/nuclearoestradiol receptor3 which may involve eosinophil migration intothe uterus.4

Department of Obstetrics and Gynaecology,St Mary’s Hospital Medical School,London W2 1PG, UK R. W. STONES

1. Stanczyk FZ, Shoupe D, Nunez V, et al. A randomized comparison of nonoralestradiol delivery in postmenopausal women. Am J Obstet Gynecol 1988; 159:1540-46.

2. Resnik R, Brink GW, Plumer MH. The effect of progesterone on estrogen-induceduterine blood flow. Am J Obstet Gynecol 1977; 128: 251-54.

3. Penney LL, Frederick RJ, Parker GW. 17-&bgr;-estradiol stimulation of uterine bloodflow in oophorectomized rabbits with complete inhibition of uterine RNAsynthesis. Endocrinology 1981; 109: 1672-76.

4. Tchernitchin A, Roorijck J, Tchernitchin X, et al. Dramatic early increase in uterineeosinophils after oestrogen administration. Nature 1974; 248: 142-43.

Acute compartment syndrome secondary totheophylline overdose

SIR,-We describe a patient who had an acute compartmentsyndrome after an overdose with aminophylline-a complicationwhich has not been previously reported.A 41-year-old woman was admitted 12 hours after taking an

unknown number of aminophylline slow-release 225 mg tablets.She was alert with a sinus tachycardia of 110 beats per minute.Abnormal laboratory findings included hypokalaemia (2-3 mmol/1),hypocalcaemia (total calcium 1-83 mmol/1, albumin 43 g/1), andneutrophilia (26-5 x 106/1). Theophylline concentration was 165mg/1 (therapeutic range 10-20 mg/1). Immediate treatment withoral activated charcoal and magnesium sulphate was instituted,together with intravenous potassium and calcium chloride.

Episodes of supraventricular tachycardia occurred, necessitatingtreatment with intravenous atenolol and cardioversion. She had

grand mal seizures which continued, together with intense musclespasms, despite diazepam and propofol sedation. Oliguric renalfailure developed with pigmented urinary casts and a creatine kinaseof over 144 000 IU/1. 40 hours after ingestion there was a secondaryrise in theophylline (figure) associated with further seizures andprofound hypotension. Charcoal haemoperfusion resulted in rapidhaemodynamic improvement and a halving of theophyllineconcentrations. Her calves were swollen and tight and the skinoverlying her anterior tibial compartments was discoloured, raisingthe possibility of acute compartment syndrome. The compartmentpressures were measured with the slit catheter technique’ whichconfirmed compartmental hypertension (right anterior 48 mm Hg,left anterior 65 mm Hg, right deep posterior 17 mm Hg, and leftdeep posterior 10 mm Hg; normal below 10 mm Hg). The patienthad immediate surgical exploration of both lower limbs throughtwo longitudinal incisions. Although the anterior tibial and peronealmuscle groups of both legs were of questionable viability there wasno obvious muscle necrosis and the tissues were left for 24 h to allowfull recovery if possible. Subsequent exploration, however, revealedcomplete muscle necrosis in the anterior compartments, and themuscles were radically excised. She made a good recovery,remained dialysis dependent until 25 days after admission, and,despite the absence of anterior tibial and peroneal muscle groups inboth legs, could walk with the aid of sticks.Acute compartment syndrome is an important, but uncommon,

clinical entity.2,3 If missed, it can lead to substantial morbidity and in

0 I . I . 1 . I . 1 . I . I . I . I

0 20 0 40 60 80 100 120 140 160 0

Time after overdose (hours)

Hourly theophylline concentrations after overdose.

severe cases amputation of the affected limbs.’ Causes includefractures, soft tissue injuries, prolonged limb compression, andarterial injuries. Although compartment syndrome after drugoverdose with barbiturates and opiates has been described,5,6 it hasnot been reported following theophylline overdose. Mechanismsinclude pressure necrosis due to prolonged limb compression,’uncontrolled muscular activity due to seizures, and possibly a directmyotoxic event.5,6 In our patient the compartmental damage wasbilateral and the patient lay in bed at home after the overdose,making pressure necrosis unlikely. The fitting was exacerbated byhypocalcaemia, a recognised feature of rhabdomyolysis-inducedrenal failure.8 We conclude that theophylline is a myotoxic drug,and that an acute compartment syndrome can, rarely, complicate itsoverdosage. Furthermore, compartmental pressure monitoring isan important clinical investigation and should be mandatory insuspected cases of acute compartment syndrome, especially in theunconscious patient.We thank Mr W. W. Barrie, Dr J. Feehally, and Dr J. Walls for theirpermission to report this patient.

Departments of Surgery, and Nephrology,Leicester General Hospital,Leicester LE5 4PW, UK

DAVID M. LLOYDSIMON P. K. PAYNECHARLES R. V. TOMSONMICHAEL R. BARNESMICHAEL J. ALLEN

1. Barnes MR, Gibson MJ, Scott J, Bentley S, Allen MJ. A technique for the long termmeasurement of intra-compartmental pressure in the lower leg. J Biomed Eng 1985,7: 35-39.

2. MacDonald JB, Jones HM, Cowan RA. Rhabdomyolysis and acute renal failure aftertheophylline overdose. Lancet 1985; i: 932-33.

3. Rumpf KW, Wagner H, Cnee CP, et al. Rhabdomyolysis after theophylline overdose.Lancet 1985; i: 1451-52.

4. Mubarak SJ, Hargens AR, eds. Compartment syndromes and Volkmann’scontracture. Monographs in clinical orthopaedics, vol III. London W B Saunders,1981: 205.

5. Richter RW, Challener YB, Pearson J, Kagen LJ, Hamilton LL, Ramsey WH. Acutemyoglobinuria associated with heroin addiction. JAMA 1971; 216: 1172-76

6. Perin AS, Rowland LP, Fraser DW Drugs, coma and myoglobinuria. Arch Neurol1972; 26: 336-43.

7. Owen CA, Mubarak SJ, Hargens AR, Rutherford L, Garetto LP, Akeson WHIntramuscular pressures with limb compression: clarification of the pathogenesis ofthe drug induced muscle compartment syndrome N Engl J Med 1979; 300:1169-72.

8. Knochel, JP. Rhabdomyolysis and myoglobinuria. In: Suki WN, Eknoyan G, edsThe kidney m systemic disease. New York: John Wiley, 1981: 263.

In-vitro production of TNF-&agr; in bloodsamples

SIR,-In a study of tumour necrosis factor (TNF-a) and open-heart surgery blood was taken during bypass when the patient isanticoagulated with heparin, and for this reason all non-bypasssamples, including preoperative and postoperative samples, werealso taken into plastic tubes with heparin. The sandwich ELISA’made use of rabbit polyclonal and mouse monoclonal antibodies torecombinant TNF-a and avidin-biotin-peroxidase complexdetection. TNF-a in phosphate-buffered saline containing 2%