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foscamet to his maintenance ganciclovir. He died six months later ofpneumonia with no evidence of active CMV disease.Case 2—A 39-year-old HIV- seropositive homosexual man was

diagnosed as having bilateral CMV retinitis. He was treatedsuccessfully with ganciclovir 10 mg/kg per day for two weeks, whichwas maintained at 5 mg/kg per day for five consecutive days everyweek. Sixteen weeks later he was admitted with a six-day history offever and hepatomegaly. Histological examination of the liverrevealed focal areas of hepatocellular necrosis, which were highlysuggestive of CMV infection; foscamet was added to his treatmentregimen. His fever settled and his hepatomegaly resolved rapidly.Repeat histological examination of the liver showed neither focalnecrosis nor evidence suggestive of persistent CMV infection.We support Nelson et al’s suggestion that refractory CMV

retinitis may respond to combinaton treatment with ganciclovir andfoscamet, and also suggest its use in CMV disease affecting otherorgans where sole therapy is ineffective. We also wish to emphasisethe importance of being alert for other systemic signs of CMVinfection despite apparent quiescence of retinal disease.

Departments of Genitourinary Medicineand Ophthalmology,

Jefferiss Wing,St Mary’s Hospital,London W2 1NY, UK

R. J. COKERD. TOMLINSONP. HORNERC. MIGDAL

J. R. W. HARRIS

Sedative and hypnotic withdrawal states inhospitalised patients

SIR,-Our psychiatric consultation service is located in a

university teaching hospital and has encountered a noticeable rise inthe cases of delirium among inpatients, which seems to be caused bysedative-hypnotic drug withdrawal. These observations have beenmade during a period when house staff were being warned againstthe routine prescription of benzodiazepines for night-time sedation.I will report one case that serves as a typical example.A 68-year-old woman was admitted to hospital for repair of a

thoraco-abdominal aneurysm. On her sixth postoperative day, shebecame acutely agitated in the early evening. Psychiatricconsultation revealed disorientation to place and time, extrememotor restlessness, paranoid delusions, and visual hallucinations.Further examination was unremarkable and a review of all

laboratory tests could not identify what caused the delirium. Thepatient was given haloperidol 5 mg intramuscularly with littlebenefit. Review of the case-notes showed that the cardiovascular

surgeon had prescribed lorazepam 2 mg for "insomnia secondary topre-operative anxiety" about 12 weeks before admission. We

thought that abrupt cessation had caused an acute benzodiazepinewithdrawal. Haloperidol was discontinued and lorazepam 2 mg atbedtime was restarted. This patient’s delirium resolved within 24 h.She later confirmed that she had been taking lorazepam regularlyfor the 12 weeks before hospital admission.This case is typical of a growing difficulty among our inpatients

and, I suspect, is not limited only to our institution. Not only shouldmedical and surgical house staff be more discriminating in theirprescription of sedative-hypnotic medications among inpatients,but they must also be vigilant as to the dangers of iatrogenicwithdrawal states.1

Sunnybrook Health Science Centre,Toronto, Ontario M4N 3M5, Canada JAY H. Moss

1. Sellers EM. Alcohol, barbiturate and benzodiazepine withdrawal syndromes: clinicalmanagement. Can Med Assoc J 1988; 139: 113-20.

Treatment of anterior tibial artery occlusion

SIR,-I was surprised that Dr Bannerjee and colleagues (June 29,p 1603) believed that their approach to anterior tibial occlusion waseither novel or an important advance. Cannulation of the tibialarteries for selective thrombolysis, augmented, when appropriate,by clot aspiration, has been a standard radiological technique formany years.’ Angiography completed with the type of fluoroscopicequipment available in many operating theatres is often less thansatisfactory. There is limited capability for recording investigations

and the quality of the fluoroscopic image is frequently poorer thanthat available in conventional angiography suites.

Although fluoroscopy may be a useful adjunct in an emergency ifsurgical embolectomy is only partly successful, a better result maybe expected when selective angiography is completed with properangiographic equipment and by experienced angiographers. Thisapproach is especially important if the procedure is likely either tobe prolonged or to require multiple aspirations and long-termthrombolytic therapy. Such procedures have long been the

province of the interventional radiologist and should continue to beso.

New England Deaconess Hospital,Boston, Massachusetts 02215, USA GEORGE G. HARTNELL

1. Traughber PD, Cook PS, Mieklos TV, Miller FJ. Intraarterial fibrinolytic therapy forpopliteal and arterial obstruction: comparison of streptokinase and urokinase. AJR1987; 149: 453-56.

SiR,—The quality of intra-operative angiograms may be inferiorto those obtained by conventional means, although failure tovisualise vessels in the lower calf in a critically ischaemic limb byconventional angiography is well recognised. However, we use asimple technique of instillation of contrast medium into either thesuperficial femoral or profunda femoris arteries during in-flowocclusion. On no occasion have we failed to show the lower tibialand plantar arteries during screening. Our equipment (PhillipsBV25 image intensifier) provides images of excellent quality, whichmay be stored on video (Phillips XTV5 HQ medical TV channel).Angiography after embolectomy will show incomplete clearance ofthrombus, which requires further embolectomy, in up to 30% ofcases.1We disagree that angiography and thrombolysis are the sole

province of the interventional radiologist. Vascular surgeons whoundertake such procedures should, like us, work in collaborationwith their radiological colleagues. Sadly, radiological supportcannot be guaranteed—and, in the UK, its absence has been themain limitation to the widespread use of intra-arterial

thrombolysis That vascular surgeons have adopted proceduresthat they label as "minimal access" is hardly surprising, but they doso sound in the knowledge that they can proceed to an openoperation in the event of failure or complications.

Department of Surgery,Worcester Royal Infirmary, Worcester WR1 5AS, UK

ANJAN K. BANERJEENICHOLAS HICKEYRICHARD DOWNING

1. Bosma HW, Jorning PJG. Intraoperative arteriography in arterial embolectomy. Eur JVasc Surg 1990; 4: 469-72.

2. Browse DJ, Barr H, Torrie EPH, Galland RB. Limitations to the widespread usage oflow dose intra-arterial thrombolysis. Eur J Vasc Surg 1991; 5: 445-49.

Late-onset homozygous protein C deficiencySiR,—The importance of protein C in haemostasis is shown by

the frequent occurrence of thrombotic disease in those with lowplasma concentrations of this factor. Hereditary protein Cdeficiency is usually but not always transmitted as an autosomaldominant trait; heterozygotes are at risk for thrombophlebitis, deepvein thrombosis (DVT), and pulmonary embolism (PE). Althoughthe homozygous deficiency state was thought to be incompatiblewith life, several adults are now known to have low plasma protein Cconcentrations but with much milder symptoms or a later onset ofdisease.1,2 However formal proof of recessive inheritance requiresconfirmatory DNA sequencing.We have previously studied a Middle Eastern family with severe

type I protein C deficiency and recurrent thrombosis (figure).3Individuals 11-6,11-7,111-1, and 111-2 (5-14% protein C activity,5-16% protein C antigen) have had recurrent DVTs and PEs. Nosymptoms of thrombotic disease are evident in 11-1,11-3, and 11-4(52-57% activity, 50-73% antigen), or in 11-5 (110% activity,105% antigen).DNA fragments from 11-7 containing the nine exons and splice

junctions of the protein C gene were amplified by the polymerasechain reaction and directly sequenced as described.4 A previouslyunidentified single nucleotide difference was found when his genesequence was compared with that of the wild-types (a homozygous