731

THE LANCET

infection SiR,—Transmission of HIV is primarily through intimate sexual with an infected individual or contact with infected blood via shared needles among intravenous drug users, occupational exposure to contaminated "sharps", or transfusions with contaminated blood products, for example. We present a case of possible HIV infection via a previously undescribed route. A 49-year-old heterosexual male was referred for evaluation of HIV seropositivity found on screening during a routine application for life insurance. A repeat ELISA and subsequent western blot were both reactive for HIV. The patient had been married for over 25 years and had three children. His wife’s serum was non-reactive for HIV antibody. He denied ever having sex with a man, nor with another woman since marriage, and claimed he had been impotent for about 10 years. He denied ever having received blood products. He had used intravenous drugs once, 3 years previously, but distinctly remembered not sharing needles but using a needle from an unopened package. On repeated questioning he adamantly denied using drugs on any other occasion. This was all independently corroborated by his wife. On a follow-up visit the patient, dissatisfied with the explanation that the alleged one-time exposure to intravenous drugs was his risk factor, inquired if contact with infected blood on cuts of the skin could lead to infection. He said that in 1982-88 he worked as a truck driver, primarily in the New York/New Jersey area. During that time he admitted that he and work colleagues would go out "gay bashing". They sought out places frequented by gay men and systematically beat them. The patient admitted doing this "too many times to count", and would frequently get large amounts of the victim’s blood on himself. He frequently sustained small lacerations on his hands while administering the beatings. On the patient’s first examination we noted several small scabbed lacerations over his proximal interphalangeal joints that had, allegedly, resulted from a recent fight. Mucocutaneous exposure to infected blood has been confirmed as the route of infection in several health-care workers with AIDS.’ One man seroconverted after contact with another’s blood when they both sustained numerous lacerations in a motor vehicle accident.2 Although we cannot prove that contact with blood from infected persons during gay bashing was the mechanism of acquisition in this case, it is certainly plausible. Perhaps this case will serve as a deterrent to the dreadful practice of "bashing" people simply because they belong to a particular minority. contact

Department of Internal Medicine, Medical Center, University of Nebraska, Omaha, Nebraska 68198, USA

PAUL CARSON JONATHAN C. GOLDSMITH

1. CDC.

Update: human immunodeficiency virus infections in health care workers exposed to blood of infected patients. MMWR 1987; 36: 285-89. 2. Hill DW. HIV infection following motor vehicle trauma in central Africa JAMA 1989; 261: 282-83.

Transiently positive HIV antibody test after treatment with tetanus immune globulin SIR,-A 25-year-old nurse injured her hand on the edge of an operating-table. She was given a prophylactic injection of tetanus immune globulin (TIG). The following day a blood sample was taken to test for hepatitis B virus (HBV) markers and HIV antibody, as is routine at this hospital in cases of possible accidental exposure to HBV and HIV. HBV markers were negative but she was anti-HIV positive with both ELISA tests used in our laboratory (Sorin Biomedica, Behring), and the same sample was western blot positive (Sorin Biomedica), showing reactivity against all viral proteins. A careful history excluded

any risk factor for HIV

infection other than hospital employment. A second blood sample, taken 12 days later, was anti-HIV negative by ELISA but showed reactivity for gp 120 and p24 by western blot. A third sample, taken 1 month after the first, was negative by both ELISA and western blot. The passive transfer of HIV antibodies

proteins have been detected in HBIG. The history and serological findings in this case suggest passive transfer of HIV antibodies by TIG given 24 hours before the first blood sample was taken. This could explain the initial reactivity, and the progressive disappearance of reactivity in western blot tests is consistent with this explanation. We could not test the TIG preparation for HIV antibody because neither lot number nor manufacturer were

HIV

"Gay bashing" as possible risk for HIV

known. A. GONNELLI P. ALMI M. RUBINO M. TOTI

Division of Infectious Diseases,

Ospedale S Maria della Scale, 53100 Siena, Italy

1. Schlench WF, Spencer SHS, Cook J, et al. Passive transfer of HIV antibody by hepatitis B immuneglobulin. JAMA 1989; 261: 411-13. 2. Wood CC, Williams AE, McNamara JG, et al. Antibody against the human immunodeficiency virus in commercial intravenous gammaglobulin preparations. Ann Intern Med 1986; 105: 536-38. 3. Lai-Goldman M, McBride JH, Howanitz PJ. Presence of HTLV III antibodies in immune serum globulin preparations. Am J Clin Pathol 1987; 87: 635-39. 4. Steele DR. HTLV III antibodies in human immune gammaglobulin. JAMA 1986; 255: 609.

Potential molecular

competitor for

SiR,—The theory of genotypic selection (ref 1 and unpublished) that a non-pathogenic HIV-1 strain might be identified

predicts

that could compete in vivo with virulent strains and ameliorate the course of disease. The phenotype of a non-pathogenic virus (which may be confused with "long-latency") should result in a symptom-free HIV-positive status. An epidemiological search of one affected population identified an individual who might be harbouring such a strain: he had HIV-1 (DNA-PCR gag, strong western blot, probable infection for longer than 10 years, no antiviral treatment), T4 lymphocyte counts about 1000/pJ, and normal mitogenic and delayed-type hypersensitivity skin test (DTH) responses. History revealed multiple high-risk contacts and intravenous drug abuse, suggesting exposure to numerous wild-type pathogenic strains from partners who subsequently died from AIDS as early as 1983. Viral growth in culture was uncharacteristically slow. This donor was negative for active hepatitis, syphilis, herpes, cytomegalovirus,

Epstein-Barr virus, toxoplasma, cryptococcus, and histoplasma. 11severely immunocompromised patients (T4 mean 66/pi) with immunological deterioration and disease progression despite zidovudine or dideoxyinosine treatment provided informed consent and agreed to discontinue all antiviral treatment. Each patient received two inoculations of blood z2-0 ml) from the putative non-pathogenic donor. Strains from symptomless donors must be characterised for competition and non-pathogenicity before inoculation. Patients have now been followed up weekly for six months and clinically 4 have improved, 3 have shown a mixed response, 3 have regressed, and 1 has died. Apart from transient myalgia, low-grade fever, and diarrhoea, no new symptoms were noted. After a zero to trace DTH response at baseline, all 10 survivors progressed to a moderate to strong response in six months (one responding to all of eight antigens and another to seven of eight), suggesting a gradual return of cell-mediated immunity.* Average total T, T4, and T8 cell numbers and percentages remained stable, fluctuating around baseline mean for six months. The above observations are paradoxical in the absence of antiviral therapy or in the presence of progressive immunological deterioration, but indicate that no harm was caused by the infusions. Importantly, an epitope of p17 (a fragment of gag product), appearing strongly in the donor strain and initially absent or weakly present in the inoculated population, subsequently increased strikingly in all patients who improved. These preliminary findings suggest a variable degree of in vivo colonisation and perhaps competition between a putative nonpathogenic strain and wild-type virulent strains. If the inoculated strain merely had a phenotype of long latency and pathogenicity, we should not have seen clinical improvement and restoration of

by hepatitis B immune

globulin (HBIG) has been demonstratedl-4 but neither HIV

nor

HIV

*Details available from The Lancet or Immuvax.

732

cell-mediated immunity as well as the absence of progressive T4-cell loss. This approach deserves further investigation. Immuvax, PO Box 481222, Los Angeles CA 90048, USA; Oncologic Institute, Los Angeles, and

MICHAEL SCOLARO ROY DURHAM GEORGE PIECZENIK

Department of Anatomy,

Mount Sinai Medical Center, New York

1. Pieczenik G. Predicting coding function from nucleotide sequence "fitness" of tRNA. Proc Natl Acad Sci USA 1980; 77: 3539-43.

or

survival of

Fetoplacental passage of 2’,3’-dideoxyinosine SIR,-Data have been reported on the fetoplacental passage of zidovudine and of its glucuronide metabolite.l,2 Other nucleoside analogues--eg, ddI (2’,3’-dideoxyinosine)-are known to have antiretroviral activity, but with few adverse effects on haematopoiesis.3 This finding may be important in view of the theoretical toxicity of zidovudine on fetal myelopoiesis. To examine if ddI given during pregnancy would damage the fetus, we attempted both to find out whether the drug crossed the placental barrier and to establish the pharmacokinetics of ddI in pregnant women. Two pregnant women aged 24 and 28 were studied; both were HIV seropositive, Centers for Disease Control stage II, and were scheduled for voluntary pregnancy termination. Length of amenorrhoea was 21 and 24 weeks, respectively. The study was approved by an independent ethical committee and patients gave written consent. Both were treated with a single oral dose of 375 mg ddI. Maternal blood was taken by venepuncture at hours 0 (before administration of ddI), 05,1,2,3,4,5,6,7,8, and 12 (after administration of ddI). Amniotic fluid and fetal blood samples were taken 65 min after treatment in patient 1 and 78 min after treatment in patient 2. Amniotic fluid was sampled by amniocentesis under untrasound control. ddI was measured by

high-performance liquid chromatography. Pregnancies were terminated by mifepristone and prostaglandin analogues. Blood samples of the two women were compared with mean concentrations obtained in non-pregnant patients.4 We found no difference in pharmacokinetics between pregnant and non-pregnant subjects. The half-life of ddI was 0 76 h in patient 1 and 118 h in patient 2. ddl crossed the placental barrier in both patients. Concentrations in fetal blood (ng/ml) were lower than those in maternal blood and the same was Maternal blood

Patient

true

Fetal

blood

for amniotic fluid: Amniotic fluid

These data show that ddI crosses the placental barrier during the second trimester of pregnancy. However, we cannot recommend ddI therapy during pregnancy until we know if the drug is toxic to the fetus.

J. C. PONS

Hôpital, Antoine Béclère 92141, Clamart, France;

Hôpital Bicêtre; and Hôpital Cochin,

Paris

M. C. BOUBON A. M. TABURET E. SINGLAS V. CHAMBRIN R. FRYDMAN E. PAPIERNIK J. F. DELFRAISSY

1. Gillet JY, Garraffo R, Abrar D, Bongain A, Lapalus P, Dellamonica P. Fetoplacental passage of zidovudine. Lancet 1989; ii: 269-70. 2. Pons JC, Taburet AM, Singlas E, Papiernik E, Delfraissy JF. Transplacental passage of azathiothymidine (AZT) during second trimester of pregnancy. Eur J Obstet

Gynaecol Reprod Biol (m press). 3. Yarchoan R, Mitsuya J, Thomas RV, et al. In vivo activity against HIV and favorable toxicity profile of 2’,3’-dideoxyinosine. Science 1989; 245: 412-15. 4.Hartman NR, Yarchoan R, Pluda JM, et al. Pharmacokinetics of 2’,3’ -dideoxyadenosine and 2’,3’-dideoxyinosine in patients with severe human immunodeficiency virus infection. Clin Pharmacol Ther 1990; 47: 647-54.

Radon in pottery workshops SiR,—Dr Bowie and Professor Bowie (Feb 16, p 409) discuss the average annual effective dose equivalents from radon indoor levels in the UK and the related risk factors for lung cancer. They stress that a link between indoor radon levels and lung cancer in the general public is not yet proved. However, until the question of the health risk of indoor radon is answered unambiguously a worst-case scenario must be assumed, especially if children are concerned. We have measured a radon level up to 740 Bq/m3 in classrooms for pottery lessons in Innsbruck. This figure is higher by a factor of 30 than the mean indoor radon level in the UK.l Although teachers and pupils are usually in the pottery room for those lessons only, the health risk to children from radon is higher than that for adults.2 A simple and effective way to avoid this risk is frequent ventilation of the rooms by opening the windows and secure storage of pottery materials in otherwise unused rooms. Institute of Medical Physics, University of Innsbruck, A-6020 Innsbruck, Austria

O. ENNEMOSER W. AMBACH

Institute of Radiochemistry, Versuchsstelle fur Strahlenschutz und Kerntechnik, Innsbruck

P. SCHNEIDER P. BRUNNER

1. Wrixon

AD, Green BMR, Lomas PR, et al. Natural radiation exposure in UK dwellings: NRPB-R190. London: HM Stationery Office, 1988. 2. American Academy of Pediatrics. Radon exposure: a hazard to children Pediatrics 1989; 83: 799-802.

Glycine and neurodegenerative disease SIR,-Excitatory aminoacid neurotransmitters (EAAs) such as glutamate have been implicated in the pathogenesis of certain neurodegenerative disorders. Glutamate analogues such as p-methylaminoalanine, p-N-oxalylamino-L-alanine, and domoic acid are neurotoxic and have been linked to neurological disorders in man." Glutamate and its analogues act at N-methyl-D-aspartate (NMDA) receptors on neurons. Glycine has an established function as an inhibitory neurotransmitter in the brainstem and spinal cord. Glycine binds to a strychnine-sensitive receptor and causes increased chloride conductance and hyperpolarisation in a similar way to y-aminobutyric acid. However, recent evidence suggests that glycine is also an allosteric modulator at the NMDA receptor, where it potentiates activity of EAAs.5 Glycine may enhance NMDA-mediated neurotoxicity. Ketotic and non-ketotic hyperglycinaemia in infants causes severe encephalopathy and seizures, and rare cases of familial non-ketotic hyperglycaemia have been reported in adults who present with a slowly progressive motor neuron disorderWe have shown that patients with sporadic motoneuron disease have increased cerebrospinal fluid (CSF) glycine concentrations and show a reduced rate of clearance of glycine from blood after an oral glycine load.7,sAmong 32 cases of motoneuron disease and 13 neurological disease controls, we found 1 patient with a significantly raised fasting blood glycine concentration. A 59-year-old woman with claustrophobia and panic attacks was treated for a few weeks in 1986 with clomipramine 20 mg at night. A few months later she noticed progressive gait ataxia followed by upper limb ataxia and slurring dysarthria, together with some impairment of memory. In March, 1988, general physical examination was normal but neurological examination revealed slight optic disc pallor, generalised mild spasticity with hyperreflexia, cerebellar signs in the limbs, and striking truncal ataxia. There was no nystagmus, plantar responses were flexor, and higher cerebral functions were intact, although she had pronounced pout and palmomental and glabellar reflexes. Investigations, which included blood film, visual evoked responses, electromyography, . CSF examination, and vitamin E measurements, were normal but brain computed tomography showed mild cerebellar atrophy. There was no evidence of malignant disease. By March, 1990, she was wheelchair-bound. She had phasic nystagmus on lateral gaze and

severe generalised limb weakness. Neuropsychological revealed testing significant cognitive decline compared with premorbid estimates. A glycine challenge test was completed.’I