BRAINSTEM HERPES VIRUS ENCEPHALITIS

690 DUAL MEANING OF MEMBERSHIP

SiR,—Dr Coleman and Dr Mant (Aug 1, p 265) criticise the Royal Colleges and Faculties in general and the Faculty of Community Medicine in particular. Their broader criticisms received a prompt and admirable response from Professor Brandon (Aug 15, p 396). However, the allegation of "blackmail" levelled at the Faculty of Community Medicine calls for a specific reply. Coleman and Mant interpret the Faculty’s standing orders on non-payment of subscription correctly up to a point. What they do not say is that the Treasurer of the Faculty is authorised to remit or reduce the registration fee and the annual or other subscription at any time at his discretion if individuals find themselves in difficulty over payment. This is a charitable gesture; such charity is not the hallmark of blackmail. Faculty of Community Medicine of the Royal Colleges of Physicians of the United Kingdom, 4 St Andrew’s Place,

MICHAEL

London NW1 4LB

Registrar

O’BRIEN,

CONFLICT OF INTEREST IN MEDICINES CONTROL

SiR,—Earlier this

year

one

of your Round the World

correspondents gave you an inaccurate report of problems that arose following allegations by a former Cilag employee about Prof Rudolf Preisig, chairman of the advisory committee to the Swiss drug regulatory agency (Interkantonale Kontrollstelle fur Heilinittel, [IKS]).1 Subsequently, Professor Preisig presented the facts known that time.2 On Aug 3 all judicial proceedings against Professor Preisig were closed. The attorney general stated that there was no evidence that he had deviated from the highest standards of integrity and unbiased, independent, critical judgment in his advisory work for IKS on the one hand and for the pharmaceutical industry (in particular for Cilag) on the other. The Canton of Berne was ordered to pay Professor Preisig’s legal fees and any expenses incurred during the judicial proceedings. An investigation within IKS by a former judge of the Federal Court concluded with an opinion identical to that of the attorney general. On Aug 21 the committee of directors of the IKS decided that Professor Preisig can continue his chairmanship of the advisory committee. The committee of directors, besides deciding upon various organisational changes (including increased staffing) within IKS, has passed regulations on the relations between members of the advisory committee and the pharmaceutical industry. These regulations are designed to protect members of the committee from future attempts at defamation. at

Interkantonale Kontrollstelle fur Heilmittel, 3000 Bern 9, Switzerland

J. PFANNER, Director

1. Anon A conflict of interest in medicines control. Lancet 1987, i: 320. 2. Preisig R. Medicines control in Switzerland Lancet 1987; i: 451.

SPECIMENS IN THE POST

SIR,-We act for a commercial medical laboratory that offers a pathology service, including screening for human immunodeficiency virus. We have been in correspondence with the Post Office’s solicitors’ department, and it has emerged that the Post Office has changed a long-standing policy on the transmission by post of pathological specimens. This change applies to all full

commercial laboratories. The Post Office will now

not

deliver any

pathological specimen posted by a member of the public, even when it is sealed and in an approved container. Under Section 11(1) (a) of the Post Office Act 1953 it is a criminal offence "to send or attempt to procure to be sent a postal package which encloses any deleterious substance or any article or thing whatsoever is likely to injure a person engaged in the business of the Post Office". Pathological specimens now come under this definition, if posted by a member of the public. The Post Office will accept specimens that have been sealed in an approved container and packaging by a recognised

laboratory or by a doctor, dentist, or veterinary surgeon.

Many commercial laboratories have hitherto been in the habit of receiving smears, blood samples, or other pathological specimens which, though taken by a qualified person, have been sealed and posted by the member of the public concerned. Such a procedure in future could, according to the Post Office’s solicitor, lead to legal proceedings. Our client considers this to be a far-reaching change reached in an arbitrary manner, and one that all medical laboratories and doctors should be

aware

of.

Hughes & Co, 16 Pittville Street, Cheltenham, Gloucestershire GL52 2LJ

JOHN M. HUGHES

MATERNAL RUBELLA AFTER 18 WEEKS

SIR,-Dr Munro and colleagues (July 25, p 201) state that their data suggest "that if there is good evidence of rubella having occurred later than the sixteenth week of pregnancy, the risk of fetal damage is very small". From fig 1, it appears that they evaluated about 15 cases of confirmed congenital rubella with proven maternal infection after 18 weeks’ gestation. The upper 95 % confidence limit ofa zero/n rate is roughly 3/n.l Thus, with only 15 patients in the denominator Munro et al could have missed a 20% frequency of congenital abnormalities with rubella infections after the 18th week. A possible 20 % risk of fetal damage should not be classified as "very small". Center for Women and Children, Toledo Hospital, and Department of Obstetrics and Medical College of Ohio, Toledo, Ohio 43699, USA 1.

Gynecology,

ROGER R. LENKE

Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? JAMA 1983; 249: 1743-45.

***This letter has been shown follows.-ED. L.

to

Dr Munro, whose

reply

disagree with Dr Lenke’s calculations, provide a basis for calculating the chance of an individual fetus escaping damage after maternal rubella at different gestational ages". The possibility that we could have missed a 20% frequency for congenital rubella defects following infections after the 18th week of gestation is based SIR,-Whilst

our

we cannot

paper did stress that the data "do not

15 cases. For the 20 children associated with infections after the 17th week (all without defects) the largest risk that could have been missed falls to 15%. Cases are reported to the programme on a voluntary basis and we are more likely to be notified of damaged than of undamaged children and of rubella exposures earlier rather than later in gestation. It would be more appropriate to apply the "zero numerator" calculation to data collected in a large prospective study of the outcome of maternal infection at differing gestational stages, such as that of Miller and colleagues.1 They reported no defects among 63 children infected after the 16th week of gestation, a possible missed incidence of rubella defects of about 5 %. on

Department of Paediatrics, University of Sheffield, Children’s Hospital,

N. D. MUNRO

Sheffield S10 2TH 1. Miller

Pollock TM. Consequences of confirmed maternal stages of pregnancy. Lancet 1982; ii: 781-84.

E, Cradock-Watson JE,

rubella

at successive

BRAINSTEM HERPES VIRUS ENCEPHALITIS

SiR,—We report here a case of herpetic brainstem encephalitis with "locked-in" syndrome and basilar thrombosis. A few hours before admission a 34-year-old man had sudden vertigo. On admission he was unconscious; noxious stimuli produced extensor responses on the left side of the body, but decorticate responses on the right. The right pupil was slightly larger than the left, both reacted to light; corneal responses were normal, as were oculocephalic and oculovestibular reflexes. The neck was supple. All the tendon reflexes were normal; both plantar

691 extensor. Respiration was irregular, and the patient by managed artificial ventilation via an endotracheal tube. The blood pressure was 130/90 mm Hg, pulse 65/min regular, temperature normal. General physical examination unremarkable. Before admission he had been in good health and there was no significant medical history. Chest X-ray, CT brain scan, ECG, blood chemistry, and liver function tests were normal. 2 h later his condition improved. He remained unconscious but had spontaneous limb movements and withdrew appropriately from noxious stimuli; the pupils were equal, and respiration was

responses

were

was

normal.

day he deteriorated with intermittent spasms of decerebrate rigidity. Cerebral angiography revealed occlusion of the basilar artery. By day 5 the patient had paralysis of both arms and both legs and the area served by the lower cranial nerves. On day 6 a CT scan showed a low-density lesion in the midbrain. Intrathecal herpes simplex virus (HSV) antibody synthesis was demonstrable with an increase in CSF/serum HSV antibody ratio. On day 7 HSV was isolated in the CSF and acyclovir (10 mg/kg 8-hourly each day for 10 days) was given intravenously. Thereafter his condition remained static and then began gradually to improve. He became progressively alert and able to communicate with some eyelid The next

Both vertical and horizontal eye movements were present. At 6 months he had normal mental status and a moderate right-sided hemiplegia. Speech was dysarthric but intelligible. Neuro-ophthalmologic signs and radiological findings indicated a lesion of the midbrain, ventral to the oculomotor nuclei. Supratentorial lesions were not seen; however, the early stage of illness suggests a cerebral localisation with impending transtentorial hemiation, which rapidly resolved with artificial ventilation. Since either viral brainstem encephalitisl or basilar thrombosis might cause a locked-in syndrome, it is difficult to assign symptoms to one or other disorders, but the likely sequence was that HSV directly caused the syndrome. However, we cannot say whether the basilar thrombosis was related to the HSV infection or the more usual causes .2

movements.

Dr A. Scalzini, department of infectious disease first suspected the HSV encephalitis; Prof A. Turano, department of microbiology, arranged for the

virological investigations. Department of Anaesthesiology and Intensive Care, University of Brescia, Brescia, Italy 1.

N. LATRONICO A. CANDIANI

Cherington M. Locked-in syndrome after ’swine flu’ inoculation.

Arch Neurol

1977;

conclude that while the association between HBV and glomerulonephritis may shed light on the pathogenesis of glomerulonephritis, the causative role of HBV in endemic areas has been overemphasised. The demonstration of viral antigens on renal biopsy is not proof of cause-and-effect. The reason why HBV does not appear to cause more cases of glomerulonephritis may be because in endemic areas exposure to HBV often occurs in infancy. Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong

M. K. CHAN

1 Sham

MK, Pun KK, Yeung CK, Ng WL, Chang WK, Chan MK Hepatitis B induced glomerulonephritis, fact or fiction? Aust NZ J Med 1985; 15: 356-58. 2. Lai KN, Lai FM, Chan KW, Chow CB, Tong KL, Vallence-Owen J. The clinico-pathologic features of hepatitis B virus-associated glomerulonephritis. Quart J Med 1987, 63: 323-33. 3. Chan MK, Lam SS, Chan PCK, Cheng IKP. Continuous ambulatory peritoneal dialysis (CAPD): Experience with the first 100 patients in a Hong Kong centre. Int J Artif Organs 1987; 10: 77-82.

SIR,-Your Aug 1 editorial argues that the association between HBV infection and glomerulonephritis is causal, a view based on the idea that circulating immune complexes are the primary cause of glomerulonephritis. For several reasons this idea is probably erroneous,’ and the conflicting reports on HBV-associated glomerulonephritis do not make it more likely. Chronic HBV and glomerulonephritis may have a common cause. Since persistence of circulating HBV antigen means that the immune system of the carrier is defective, the factor to blame may be one which is both immunotoxic and nephritogenic. Certain chemicals meet this description, and there is evidence that they are responsible in many cases.23 The frequency of tubulointerstitial lesions in glomerulonephritis accords well with this finding because most nephritogenic chemicals are also tubulotoxic; renal function and clinical course are better predicted by tubulointerstitial than by glomerular changes.4 Most nephritogenic chemicals (eg, hydrocarbons, gold, mercury, and silicon) are immunotoxic,4 possibly explaining the immune defects found in a large proportion of patients.’ One could argue that toxic exposure is unlikely in HBV-associated glomerulonephritis because most patients are children. But in a study of another glomerulonephritis subgroup questioning after such exposure revealed that children may be exposed.5 The primary goal in HBV-associated glomerulonephritis may be to detect and eliminate immunotoxic and nephrotoxic factors, not to treat their consequences.

34: 258.

CS, Adams RD. Occlusion of the basilar study. Brain 1946; 69: 73-121.

2 Kubik

artery. A clinical and

pathological

Olshogsv 14, S-223 60 Lund, Sweden

U. RAVNSKOV

1. Couser WG. What

HEPATITIS B VIRUS AND GLOMERULONEPHRITIS

SIR,-Your Aug 1 editorial on hepatitis B virus (HBV) and glomerulonephritis rightly concludes that the issue is "of more than theoretical importance". Unfortunately, the possible socioeconomic impact of HBV-induced glomerulonephritis was not mentioned. As you say, glomerulonephritis is the commonest cause of renal failure leading to dialysis. In Hong Kong HBV is endemic, the HBsAg carrier rate being close to 10%. If HBV is an important cause of glomerulonephritis, and if HBV-induced glomerulonephritis leads to renal failure, nephrologists in Hong Kong would face a big problem. However, our experience1.2 is very different. While accepting that HBV is likely to be a cause of membranous glomerulonephritis (we found that the frequency of HBsAg in male patients with membranous glomerulonephritis was four times that of the general population) we concluded that HBV does not cause glomerulonephritis of endemic proportions. The number of cases of membranous glomerulonephritis associated with HBsAg was small, only 15/378 (4%), and among patients with end-stage renal failure (serum creatinine above 1000 limol/1) only 7-1 % were HBsAg positive. HBsAg-positive patients have been regularly accepted for maintenance dialysis at our unit since 1983, and in the first 100 patients treated with peritoneal dialysis there were 10 HBsAg-positive patients.3 The frequency of HBsAg carriage is thus almost identical to that of the general population. We

are circulating immune complexes doing in glomerulonephritis? N Engl J Med 1981; 304: 1230-32. 2. Churchill DN, Fine A, Gault MH. Association between hydrocarbon exposure and glomerulonephritis. An appraisal of the evidence Nephron 1983; 33: 169-72. 3. Bell GM, Gordon ACH, Lee P, et al. Proliferative glomerulonephritis and exposure to organic solvents. Nephron 1985; 40: 161-65. 4. Ravnskov U. Possible mechanisms of hydrocarbon-associated glomerulonephritis. Clin Nephrol 1985; 23: 294-98. 5 Ravnskov U. Exposure to organic solvents a missing link in poststreptococcal glomerulonephritis? Acta Med Scand 1978; 203: 351-56.

SiRj—The pathogenetic mechanism of HBV antigenaemia in inducing glomerulonephritis remains speculative. Immunecomplex mediated glomerular injury is a distinct possibility since circulating immune complexes are found in sera from patients with HBV-associated glomerulonephritis.12 Membranous nephropathy is the commonest pathological entity in HBV-associated glomerulonephritis. Japanese workers have found deposits of HBeAg along the basement membrane without HBsAg3,4 but HBsAg and/or HBcAg have been reported separately by others.5Þ In our recent studies, the monospecificity of the staining for HBV antigens was checked by blocking and absorption procedures.6,7 We failed to demonstrate HBeAg in renal biopsy tissue using the polyclonal antiserum. The difference between our observations6 and those of Hirose and co-workers’ could well be due to the difference of specificity of antisera or the properties of the antigen.