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the 4 infertile women conceived. Galactorrhoea was alleviated in 6 of 11women with this complaint. Minor side-effects occurred in only three instances-transient nausea in 1 woman and vaginal irritation in 2. Administration of bromocriptine by the vaginal route avoids the adverse side-effects of oral therapy. In many instances this route could be used as first-line treatment. The development of a sustained-release preparation, as produced for oestriol8 or progestagens,9 would considerably improve compliance.

CLINICAL FEATURES OF THREE FATAL CASES

out

Departments of Endocrinology, and Chemical Pathology, Royal Free Hospital Medical School and Royal Free Hampstead NHS Trust, London NW3 2QB, UK

JEAN GINSBURG PAUL HARDIMAN MICHAEL THOMAS

Kocijancic A, Prezel JJ, Vrhovec I, Lancranjan I. Parlodel LAR in the treatment of macroprolactinomas. Acta Endocrinol Copenh 1990; 122; 272-76. 2. Cuellar FG. Bromocriptine mesylate (Parlodel) in the management of amenorrhoea/ galactorrhoea associated with hyperprolactinaemia. Obstet Gynecol 1980; 55: 1

278-84. 3. Vermesh M, Fossum GT, Kletzky OA. Vaginal bromocriptine: pharmacology and effect on serum prolactin in normal women. Obstet Gynecol 1988; 72: 693-98. 4. Katz E, Schran HF, Weiss BE, Adashi EY, Hassell A. Increased circulating levels of bromocriptine after vaginal compared with oral administration. Fertil Steril 1991; 55: 882-84. 5. Katz E, Schran HF, Adashi EY. Successful treatment of a prolactin-producing pituitary macroadenoma with intravaginal bromocriptine mesylate: a novel approach to intolerance of oral therapy. Obstet Gynecol 1989; 73: 517-20. 6. Kletzky OA, Vermesh M. Effectiveness of vaginal bromocriptine m treating women with hyperprolactinaemia. Fertil Steril 1989; 51: 269-72. 7. Schran HF, Schwarz HJ, Talbot KC, Loeffler LJ. Specific radioimmunoassay of ergot peptide alkaloids in plasma. Clin Chem 1979; 25: 1928-33. 8. Diczfalusy E, Landgren BM. New delivery systems vaginal rings. In: Chang CF, Griffin D, Woolman A, eds. Recent advances in fertility regulation. Geneva. Arar 9.

SA, 1981: 43-69. Ginsburg J, O’Reilly B, Fink RS, Collms WP, Weiss P. Hormonal effects of a new sustained release vaginal oestriol pessary J Gynaecol Endocrinol 1987; 1: 1-7.

Malignant hyperthermia and Hirschsprung’s disease SIR,-Malignant hyperthermia (MH) is a familial disease with genetic inheritance. However, Brownell/ in a comprehensive review, found that patients with King-Denborough syndrome, Duchenne muscular dystrophy, and central core disease are susceptible to MH; and Peterson and Davis2 and Denborough et a13 have described an association of sudden infant death syndrome (SIDS) with MH. We report here a possible link with Hirschsprung’s disease. Between September, 1983, and August, 1990, 20 cases of Hirschsprung’s disease in 17 males and 3 females aged 11days to 5 years were seen. The diagnosis was confirmed by the absence of myenteric parasympathetic ganglia on histological examination of a full-thickness rectal wall biopsy specimen. The 9 patients treated by a completely diverting transverse colostomy and a definitive Swenson’s pull-through procedure 6-14 months later, under general anaesthesia, are the focus of this letter. As a result of a third perioperative death from MH among 6 patients operated on between March, 1985, and October, 1987, we stopped using succinylcholine and halothane, which are known triggering agents for MH. We replaced these agents with pancuronium, droperidol, barbiturates, nitrous oxide, and morphine for general anaesthesia in all subsequent operations on patients with Hirschsprung’s disease. In the next 3 patients managed by Swenson’s procedure there has been no MH. The 1 postoperative death was due to wound complications. Interview of the families of all these patients revealed no history ofMH. Details of the 3 fatal cases are given in the table. In case 1 MH was suspected during closure of the abdominal wound after completion of perineal anastomosis 1hours after multifactorial

induction of anaesthesia. The bowel was very hot and the muscle was too rigid for the wound to be approximated. There was tachycardia and irregular pulse. The skin was mottled, and lips and nail beds were cyanosed. The urine output within the 12h was 55 ml and pH was 4-7. Halothane was discontinued and anaesthesia maintained with nitrous oxide, pancuronium, and oxygen. Sodium bicarbonate 3 mg/kg was given intravenously. Surface cooling with iced water and nasogastric lavage with iced saline were started. The

temperature fell to 38’2°C and the procedure was completed. When this patient’s temperature rose again in the intensive care unit he did not respond to symptomatic treatment. He had convulsion and remained unconscious until death 8 hours postoperatively. The other 2 cases had similar presentations (but no convulsions) and management. 1 died during the operation and the other died 2 hours after surgery. Hirschsprung’s disease is a common cause of large bowel obstruction in infants and children in Port Harcourt, Nigeria.4 The 5 patients who survived the definitive Swenson procedure all have a good result functionally. However, perioperative mortality was high (44%) and 3 of the 4 deaths were due to fuhninant intraoperative MH. Since there was no family history of MH and no evidence of concurrent infections, we feel that patients with Hirschsprung’s disease are unusually susceptible to MH. Hyperthermia was not observed in infants and children operated on for other conditions during the same period and MH was not encountered when we stopped using the triggering agents succinylcholine and halothane for anaesthesia in subsequent Swenson procedures. Triggering agents apart, mechanical stimulation of the splanchnic sympathetic nervous system may have led to increased release of catecholamines and thus potentiated or caused MH in these patients. The MH developed during or immediately after the manipulation and resection of the aganglionic segment of colorectum, which is rich in sympathetic nervous supply. MH did not develop when transverse colostomy was done under such anaesthesia, probably because the aganglionic part of the colorectum was not manipulated. Mortality from MH in cases treated symptomatically remains high even if the diagnosis is made early (28%).’ The case-fatality rate has been reduced to 10%5 when dantrolene was used early in conjunction with symptomatic treatment.5,6 Our 3 fatal cases received late symptomatic treatment and dantrolene was not available. Departments of Surgery and Anaesthesia, University of Port Harcourt, PO Box 450 Choba,

EDWIN N. ELECHI

Teaching Hospital, Port Harcourt, Nigeria

P. DAKARAJU

1. Brownell AKW. Malignant hyperthermia: relationship to other diseases. Br J Anaesth 1988; 60: 303. 2. Peterson DR, Davis N. Malignant hyperthermia diathesis and sudden infant death syndrome. Anaesth Analg 1986; 65: 209-13.

3. Denborough MA, Galloway GJ, Hopkinson KC. Malignant hyperpyrexia and sudden infant death Lancet 1982; ii: 1068-69. 4. Elechi EN. Gastrointestinal obstructions experience in Port Harcourt, Nigeria. Br J Clin Pract 1988; 42: 364-67. 5. Ranklev E, Fletcher R. Investigation of malignant hyperthermia in Sweden. Acta Anaesth Scand 1986; 30: 693. 6. Kolb ME, Home ML, Martx R. Dantrolene in human malignant hyperthermia: a multicenter study. Anaesthesiology 1982; 56: 254-62.

Lysis of middle-cerebral-artery occlusion with alteplase SiR,—Occlusion of the middle cerebral artery (MCA) has a very poor prognosis. Recanalisation within 3 h of the stroke may prevent severe neurological damage, so any therapeutic procedure must be done quickly. Local injection of a fibrinolytic agent via an arterial catheter proximal to the thrombus is widely used for thrombolysis in myocardial infarction. In this percutaneous transluminal coronary recanalisation, tissue plasminogen activator (tPA) shows greater clot selectivity than streptokinase or urokinase. The use of tPA in brain infarcts is controversial, even when the agent is given systemically, though intra-arterial administration for basilar artery occlusion has been reported.’ We describe here the emergency

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artery. 10 min after the procedure the neurological picture was unchanged and haematuria occurred. With further informed consent, we administered 20-7 mg tPA in the same manner. Soon after the procedure, the patient’s left leg moved and a repeat arteriogram revealed partial recanalisation of the MCA. So we then administered 17mg tPA over 60 min (total dose 0 58 mg/kg). Arteriography 163 min after onset of the stroke showed complete recanalisation (fig 2). Further treatment consisted of heparin and 42 h of barbiturate therapy (3 mg/kg/h). Cranial computerised tomographic scans 3 and 18 h after fibrinolysis did not reveal any haemorrhagic complications; a right cerebral small infarct became clear in scans after 43 h. The patient regained consciousness after 4 days and was extubated on day 5 with no neurological deficit. Departments of Cardiovascular Surgery and Neurosurgery, Kitaibaraki City Hospital, Ibaraki, Japan

JUNICHI SAKURAI TAIHEI EGASHIRA YUZO YAMADA NOBUTAKA NOMURA

1. Henze T, Boeer A, Tebbe U, Romatowski J. Lysis of basilar artery occlusion with tissue plasminogen activator. Lancet 1987; ii: 1391.

Whiplash injury SIR,-Dr Radanov and colleagues (Sept 21, p 712) and your (p 728) do not clearly define the injury mechanism of whiplash. Radanov et al refer to non-contact trauma involving editorial

and exclude people with loss of consciousness. In your editorial you refer to studies in the 1960s and at that time neck supports were not usually fitted in cars. Whiplash injury as originally described-starting with hyperextension-is very rare today, since almost all cars now have neck supports. Usually a whiplash injury, especially in rear-end collisions, involves a head-neck trauma on the neck support followed by hyperflexion. Therefore, I do not understand Radanov and colleagues’ reference to non-contact trauma. Their patients will probably also have struck their head on the neck support. Chronic headache and some symptoms such as dizziness and blurring of vision can arise and persist, despite the fact that there is no loss of consciousness. This was especially true when neck supports were not present. One should remember, however, that any head trauma (except when the head is hit by two opposite and equal forces) entails a traumatic bump or pull on the neck. With colleagues, I have shown that the headache index in 19 patients with post-traumatic headache was inversely correlated with the extension-flexion motion of the neck’ and positively correlated with dizziness and some eye and ear symptoms.2 One might speculate, which of the so-called postconcussional symptoms arise from the neck and which from the brain?

hyperextension/hyperflexion,

Fig 1-Total occlusion of MCA before tPA. of a patient with an MCA thrombosis using tPA via (alteplase) a catheter in the left internal carotid artery. A 69-year-old man with a history of myocardial infarction and unstable angina suddenly became comatose with right-sided hemiplegia coinciding with atrial fibrillation while on the table of a cineangiography room after coronary arteriography. He was breathing spontaneously via a nasotracheal tube and his eyes deviated to the left. Left cerebral arteriography revealed MCA occlusion (fig 1).With the informed consent of the patient’s relatives we gave a continuous injection of 240 000 units urokinase via the catheter placed in the petrous portion of the left internal carotid treatment

Department of Rheumatology, Aarhus Amtssygehus, 8000 Aarhus C, Denmark

OLE KUDSK JENSEN

1.

Jensen OK, Justesen T, Nielsen FF, Brixen K. Functional radiographic examination of the cervical spine in patients with post-traumatic headache. Cephalalgia 1990; 10:

2.

Jensen OK, Nielsen FF, Vosmar L. An open study comparing manual therapy with the use of cold packs in the treatment of post-traumatic headache. Cephalalgia 1990;

295-303.

10: 241-50.

Fig 2-Complete recanalisation.

SIR,-Your Sept 21 editorial, commenting on Dr Radanov and colleagues’ report, ignores several observations basic to the understanding of the post-traumatic syndrome, generally known as whiplash injury. The experiments in animals are irrelevant to the syndrome, since monkeys cannot complain of the symptoms of whiplash. The extrapolation from experimental injuries, sometimes severe enough to avulse tendons, is invalid, since whiplash does not occur in severe injuries. In fact, this syndrome is commonly seen in patients with no head injury and with a well supported head rest on their car seat. Tinnitus, deafness, and nystagmus rarely (if ever) occur in whiplash, and careful history-taking indicates that dizziness is the vague subjective disturbance seen in anxiety states or depression, and is not true vertigo. The main features of the syndrome,