695

Their clinical

remained

satisfactory, except in one in whom developed; opportunistic infections did not Kaposi’s occur. However, even though CD4 cell counts were stabilised over the treatment period, specific cellular immune responses to HIV or to recall antigens (PPD, candidin) were not restored,’ as if the proliferation of specific T-cell clones that characterise such responses had been inhibited (cytostasis) by HIV infection. This limitation prompted us to design a new strategy for vaccine therapy aiming at overcoming the cytostasis. A description of this second generation immunotherapy and preliminary clinical results showing partial restoration of cellular immunity in HIV-infected immunodeficient patients will be published. status

sarcoma

Université Pierre et Marie Curie, 75005 Paris, France

D. ZAGURY

P, Defer MC, et al. AIDS vaccine therapy: phase I trial Lancet 1990; 336: 179. 2. Picard O, Lebas J, Imbert JC, Bigel P, Zagury D. J AIDS 1991; 4: 641-43. 3. Guillaume JC, Salag P, Wechsler J, Lescs MC, Roujeau JC. Vaccinia from recombinant virus expressing HIV genes. Lancet 1991; 337: 1034-35. 1. Picard O, Giral

Safe

are

unacceptably

common

among

health-care workers. Since recapping used needles is the most frequent cause of needlestick injuries, the Centers for Disease Control (CDC) issued a policy in 1987 recommending that used needles should be discarded without recapping.l However, after serious controversy over this recommendation, several safe-needle devices were developed and tried.2 None of the proposed preventive methods has gained wide acceptance. I therefore submit the following solution. After uncapping the needle, the cap should be placed on the side-table or bed with the open end facing the health worker. Once used the tip is guided back into the cap, with the operator keeping his hands behind the needle, while the cap remains untouched on the side-table or bed. After the needle tip re-enters the cap, it is angled upwards allowing the loose cap to slide down the needle shaft covering it completely. Finally, the needle is wedged into the cap by pushing it against the side of the table or bed until it snaps. In the two years since I have developed this method, I have been

able

to

teach it

to

several

nurses

and medical students. The

technique proved easy to learn and quickly replaced the traditional way of recapping with both hands. Others’have independently proposed a similar method.3 This skill is simple, practical, and easy to learn and does not require additional devices or the movement of hands towards the sharp ends of used needles. It could, if coupled with appropriate education of all concerned,’ help to reduce accidental needlestick injuries. University of Oklahoma Health Sciences Center, and Mercy Health Center, Oklahoma City, Oklahoma 73120, USA

or

thrombosis) and (2) amniotic puncture before peritoneal space (Dr Shepard and colleagues,

obliteration of the

May 4, p 1092). We use the ’Chorionscope’ (Wolf, Knittlingen, Germany) for CVS. This instrument operates transcervically with a lateral approach to chorionic villi, which are cut and colic cted under direct vision.1 Villi are normally taken from the margin of the placenta, where only few vascular villi are present and perforation of the amnion is impossible. Among 100 children born after chorionscopic CVS we found 1 case of transverse limb reduction. The mother was 38 years old with two previous pregnancies. CVS was done at 11 weeks plus 1 day (78 days) gestational age. The placenta was attached low posteriorly. 20 mg vascular villi were, unusually, sampled from chorion frondosum, near the implantation site of the placenta. After an uneventful pregnancy a baby girl was born with hypoplasia of the 4th and 5th finger of the right hand, absence of two distal phalanges of these fmgers, and syndactily of the 3rd, 4th, and 5th finger. No inherited hand malformations were recorded in the

family. In this case we can exclude both chorion and amnion perforation. However, vascular disruption after the critical period of 66 days might have taken place, with less severe consequences because of the advanced gestational age. We do not believe that puncture of the

recapping of used needles

SIR,-Needlestick injuries

haemorrhage

H. SAADAH

1. Centers for Disease Control. Recommendation for prevention of HIV transmission in health-care settings. MMWR 1987; 36 (suppl): 3S-18S. 2. Goldwater P, Law R, Nixon A, Officer J, Cleland J. Impact of a recapping device on venepuncture-related needlestick injury. Infect Control Hosp Epidemiol 1989; 10: 21-25. 3. Coiner C. Compliance with needle disposal policies. Am J Infect Control 1989; 17: 44-45. 4. Wright G, Farrer J. Potential for the prevention of "needle-stick" injuries in hospitals.

Med J Aust 1990; 152: 111-12. 5. Becker M, Janz N, Band J, Bartley J, Snyder M, Gaynes R. Noncompliance with universal precautions policy: why do physicians and nurses recap needles? Am J Infect Control 1990; 18: 232-39. 6. Jagger J, Hunt EH, Pearson RD. Recapping used needles: is it worse than the alternative? J Infect Dis 1990; 162: 784-85.

Exocoelomic space, limb reduction, and CVS SiR,—After Dr Firth and colleagues’ report (March 30, p 762), limb defects have been recorded as a possible complication of chorionic villus sampling (CVS) between 56 and 66 days, although Dr Monni and colleagues’ (May 4, p 1091) record some cases when CVSwas done later in pregnancy. Two main aetiological mechanisms are proposed: (1) vascular disruption (chorionic

amniotic sac is relevant in these disruptions. In transabdominal CVS, puncture of the amnion is certainly more frequent. The amnion is resistant to perforation; chorion perforation and insertion of an endoscope into the peritoneal space seem to be harmless.2 CVS is only suspected to cause limb defects. Nevertheless, we emphasise the need for investigation of the placenta after birth (eg, absence of a cotyledon in the sampling site) and avoidance of sampling at the placenta implantation site, before drawing conclusions about the possible role of CVS in limb reduction. Division of Obstetrics and Gynaecology, Franchini Hospital, I-42027 Montecchio Emilia, Italy

Laboratory of

G. GHIRARDINI

Cytogenetics, L. CAMURRI

USL 9, Reggio Emilia

1. Ghirardini G, et al Chorionic villi sampling by means of a new endoscopic device. In: Fraccaro F, Simoni G, Brambati B, eds. First trimester fetal diagnosis. Berlin: Springer Verlag, 1985. 2. Ghirardini G. Embryoscopy. old technique new foe in the 1990s? Am J Obstet Gynecol 1991; 164: 1361-62.

antibody HA-1A for gram-negative shock

Monoclonal

SIR,-Dr Lehner and Dr Cohen, and Dr Boardman (April 27, p 1036) comment about HA-1A (’Centoxin’) and its clinical use. HA-IA is a human IgM monoclonal antibody that binds specifically to the lipid A moiety of endotoxin. The clinical trial of HA-1A was designed with the expectation that the drug would, therefore, be most effective in patients with endotoxaemia.1 In the absence of a practical bedside test for endotoxin, gram-negative bacteraemia (GNB) is a good clinical surrogate for endotoxaemia2.3 and patients with this condition were therefore chosen prospectively as a group of primary interest for analysis. Thus the main objective of the trial, as stated in the protocol, was to show a reduction of mortality in septic patients with GNB. The frequency of endotoxaemia was measured in a subset of patients and was highly correlated with GNB. The reduction in mortality was highest in the group with endotoxaemia, as would be expected for an antiendotoxin antibody.4 Although there were numerical differences between HA-IA and placebo, in various subgroups of patients without gram-negative infection, none of these differences was significant. HA-1A has been shown to be safe in the treatment of septic patients. Transient flushing, localised urticaria, and hypotension only have been reported and are rare (=$1%) in patients receiving HA-IA. Antibodies against HA-1A have not been detected. It is also reassuring that HA-IA has now been given safely to nearly 1000 patients world wide. The entry criteria used in the clinical trial of HA-IA selected

a

patient population with a 37% frequency of GNB. We believe that

696

by focusing the use of HA-IA on diseases that are predominantly caused by gram-negative organisms, the positive predictive value of these criteria can be improved. From our subsequent open label trial and assessment of select patient types from the original trial there is evidence that doctors can predict GNB about 50% of the time. These patient types have sepsis with either shock, nosocomial pneumonia, peritonitis complicating abdominal surgery or trauma, or wound or soft tissue infection complicating surgery or multiple trauma. We agree that better predictors for endotoxaemia are needed. However, even without these tests, and with the clinical criteria described here, we believe that there is a very high benefit-to-risk ratio for use of HA-IA in septic patients with a presumptive diagnosis of gram-negative bacteraemia, especially those with septic shock. Economic analyses have shown that HA-IA is a highly cost-effective treatment compared with many routine medical practices. The mechanism of action of HA-IA has lately been widely studied. Information is emerging that explains why investigation of the mechanism of action in certain animal models has been so difficult. The data suggest that HA-IA prevents activation of inflammatory mediators in vitro and enhances the normal mechanism for clearance of endotoxin from the circulation in man.

Centocor, Malvern, Pennsylvania 19355, USA

CRAIG SMITH CORNELIUS WORTEL WENDY DIXON

University of California, San Diego

ELIZABETH ZIEGLER

Ziegler EJ, Fisher CJ Jr, Sprung CL, et al. Treatment of Gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. N Engl J Med 1991; 324: 429-36. 2. van Deventer SJH, ten Cate JWT, Buller HR, Sturk A, Pauw W. Endotoxaemia: an early predictor of septicaemia in febrile patients. Lancet 1988; i: 605-09. 1.

3. Stumacher JR, Kovnat NJ, McCabe WR. Limitations of the usefulness of the limulus assay for endotoxin. N Engl J Med 1973; 288: 1261-64. 4. Wortel C, Sprung C, van Deventer S, Lubbars M, ten Cate J. Anti-endotoxin treatment with HA-1A: possible mechanism of beneficial effects in patients with Gram-negative septicaemia. International Congress for Infectious Diseases.

Montreal, Canada, July 15-19, 1990 (abstract 495).

Malignant mesothelioma after exposure to asbestos in dental practice SiR,—There is a well-recognised association between exposure asbestos and the development of malignant mesothelioma.’1 Occupational exposure often results in the development of this disease after 30-45 years’ latency.’ In some occupations the exposure to asbestos may be slight or transitory. Unlike the association between high levels of asbestos exposure and asbestosis, the amount of exposure, particularly to crocidolite (blue asbestos), leading to malignant mesothelioma may be relatively small.’ We report malignant mesothelioma in a dental practitioner after to

exposure to crocidolite asbestos fibres.

A 60-year-old retired dentist presented with recurrent left pleural effusions. Malignant cells highly suggestive of mesothelioma were seen in aspirates, and he subsequently underwent a left pleurectomy. Histology of the resected material confirmed malignant mesothelioma. His condition deteriorated, paraplegia developed, and he died 10 months after presentation. At postmortem examination the left pleural cavity was replaced by firm white tumour, which surrounded the left lung and extended into the interlobar fissures, pericardial cavity, chest wall, and paravertebral tissue. Histological examination showed a malignant mesothelioma of mixed type. Mineral analysis of lung tissue revealed 0-7 x 1066 crocidolite fibres per gram of dry lung. This amount of crocidolite is not as high as would be expected in a case associated with longstanding occupational exposure, but represents a greater level of exposure than in the general population. Asbestos is a generic term for several hydrated silicate minerals, which are commercially available as serpentine fibres, of which chrysotile is the type most commonly used, and as amphibole fibres, of which crocidolite is an example. Crocidolite is substantially more oncogenic than chrysolite. However, both fibre types have a dose-response relation to the development of malignant

mesothelioma.4 Until the mid 1970s paper and powder containing these fibres were used, respectively, in the manufacture of metal prostheses (fillings) and as a binder in periodontal dressing. In the first procedure the paper was used to line casting rings and crucibles. It was supplied on large dry rolls, from which crocidolite fibres were readily released into the air. Liners were also used for casting dentures. During heat treatment the asbestos became brittle and consequently between 21 and 27 fibres per ml of air were released on dismantling of the moulds.s This contrasts with the current UK regulations of release of 0-6 fibres crocidolite per ml air; and 1 ’5 fibres chrysotile per ml air in 10 min.6 In the past it was common practice for undergraduates at dental schools to cast a minimum of 40 sets of dentures. This is likely to have exposed large numbers of dentists to airborne asbestos fibres, even if they were infrequently exposed subsequently. The risk to dental technicians who would have been exposed for longer periods would be greater, and 20 years ago one of us saw pleural mesothelioma in a dental technician (J. S. P. J., unpublished). The dust from the dry rolls of asbestos paper was a further source of exposure and may continue to be so if there are forgotten stores of paper. There was no formal protocol for its disposal when the danger was realised. Periodontal dressings were prepared from a powder in which chrysotile asbestos acted as a binding agent and there was a risk of inhaling airborne fibres during the mixing of the materialThe potential danger to dental personnel was realised and such products were no longer accepted in the USA after 1976. The danger to the patient was regarded as negligible.7 The use of such dressings was apparently confined to specialist dental practices in the UK. In our patient chrysotile fibres were not found in the lung tissues. However, this may be consistent with a clearance effect.4 Asbestos has now been replaced by kaolin and aluminium hydroxide. In our patient the Health and Safety Executive found no other source of exposure to asbestos, and no previous reports of malignant mesothelioma in dental personnel. This first reported case thus illustrates another potential occupational association between asbestos exposure and mesothelioma. We thank Prof A. E. Tattersfield for permission to report this case, Dr Allen Gibbs and Mr M. Griffiths for the mineral analysis of post-mortem lung tissue, Mr F. D. Beggs, Prof M. Braden, and Mr M. E. Pendlebury for advice on dental practice and references, and Dr Alan Scott (Nottingham Health and Safety Executive).

Department of Histopathology, City Hospital, Nottingham NG5 1 PB, UK, and Bio-materials Laboratory, Kings College Medical School, London SE5

A. S. REID B. E. CAUSTON J. S. P. JONES I. O. ELLIS

1. Hillerdal G.

Malignant mesothelioma 1982: review of 4710 published cases. Br J Dis Chest 1983; 77: 321-43. 2. Chen W, Mottet NK. Malignant mesothelioma with minimal asbestos exposure. Hum Pathol 1978; 9: 253-58. 3. Bashar Bakdash M, Frydman A. Asbestos m periodontal dressings: a possible health hazard. Quint Intern 1976; 10: 61-65. 4. Rogers AJ, Leigh J, Berry G, Ferguson DA, Mulder HB, Ackad M. Relationship between lung asbestos fiber type and concentration and relative nsk of mesothelioma. Cancer 1991; 67: 1912-20. 5. Brune D, Beltesbrekke H. Levels of methylmethacrylate, formaldehyde and asbestos in dental workroom air. Scand J Dent Res 1981; 89: 113-16. 6. Control of asbestos at work regulations 1987. S.I. 1987/2115 as amended by S I. 1988/712. London: HM Stationery Office, 1987. 7. Council on Dental Therapeutics. Hazards of asbestos in dentistry. J Am Dent Assoc 1976; 92: 777-78.

Aortic

distensibility

SiR,—Dr Dart and colleagues (Aug 3, p 270) and your editorial in same issue (p 288) explain that techniques such as echocardiography permit the measurement of systolic-diastolic changes of diameter in the thoracic aorta. It is suggested that the state of comparatively accessible parts of the circulation, such as the transverse aortic arch, can tell us about the less accessible coronary arteries, for example. the

These and similar papers show a lack of understanding of the function of the aorta. The characteristic of this vessel that is essential to its function is not distensibility (or the previously fashionable

Monoclonal antibody HA-1A for gram-negative shock.

695 Their clinical remained satisfactory, except in one in whom developed; opportunistic infections did not Kaposi’s occur. However, even though CD...
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