551

ICU OUTCOMEAND MEAN DA!LYT!SSATGUY’SHOSP!TAL, 1991

In our unit, only when TISS is more than 40 points do we see such a mortality rate (table). Moreover, in the past six months, the mean daily TISS for patients with APACHE II scores of 15-25 at Guy’s was 38 points. The discrepancy between mortality and TISS in the Argentinian study casts doubt on whether their small changes in therapy, guided by pHi measurement, were likely to have had any discernible effect on outcome. Another point concerns the substantial proportion of patients, 44% in this study and 38% in their previous study,l in whom pHi deteriorated over the first 24 h despite therapy. This is in striking contrast to our own findings in which only 8 % of patients showed this pattem.2 Even more disconcertingly, no improvement in survival could be demonstrated in the group with a low pHi on admission, despite the fact that in Gutierrez and co-workers’ previous report1 patients in whom a low pHi became normal over 12 h had a pronounced reduction in mortality rate (65-4% to 36-4%). We have been able to confirm this observation, and the lack of effect of their treatment protocol in this high-risk group casts doubt on its ability to alter pHi. We believe that this study demonstrates little more than the

prognostic importance of pHi

in critically ill patients and fails to resolve the issue of whether its manipulation improves outcome.

Departments of Surgery and Guy’s Hospital,

Intensive Care,

London SE1 9RT, UK

NICHOLAS MAYNARD RICHARD BEALE MARK SMITHIES DAVID BIHARI

favour of an experimental HIV vaccine.3 Another showed that four patients with pneumonia developed severe bone-marrow aplasia 12 weeks after initiation of AZT; three recovered within 4 weeks of discontinuation of the drug.4 Moreover, there is no proof that HIV causes AIDS.l It follows that AZT therapy for antibody-positive persons is indeed a "cause for concern". In view of this I can understand why Wellcome, the producer of AZT, declined an invitation to discuss these concerns with Meditel, the programme’s producers, but it seems arrogant for medical scientists running the Anglo-French Concorde trial of AZT to decline as well. Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA

Duesberg PH. AIDS epidemiology: inconsistencies with human immunodeficiency virus and with infectious disease. Proc Natl Acad Sci USA 1991; 88: 1575-79. 2. Duesberg PH. The role of drugs in the origin of AIDS. Biomed Phamacother 1992; 46: 1.

3-15. 3. Scolaro M, Durham R, Pieczenik G. Potential molecular competitor for HIV. Lancet 1991; 337: 731-32. 4. Gill PS, Rarick M, Byrnes RK, Causey D, Loureiro C, Levme AM. Azidothymidine associated with bone marrow failure in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1987; 107: 502-05.

HIV

Paid donations

HlVpositive No Rate (per 105) Risk ratio (and 95%

(in press).

HIV

as

Scoring System: update 1983. Crit

target for zidovudine

SIR,-Your note (Feb 15, p 421) on a British television documentary on zidovudine (azidothymidine, AZT) asserts that HIV undergoes antigenic drift and "is constantly able to escape" neutralising antibodies and is thus a legitimate target for AZT

therapy. A legitimate target is one that is susceptible to DNA chain termination by AZT because it is actively engaged in DNA synthesis. However, there is no evidence that HIV drifts antigenically in antibody-positive persons, in the presence or absence of AZT. For example, the "AID S test" only works because antibodies against HIV from all virus carriers react with the same patented, standard HIV strain. Indeed, only a minority of viral antigens can drift without eliminating the viability of a virus, which is the reason that vaccines work. If viruses in general could evade immunity by antigenic drift, the immune system would be little more than a vestigial burden to the host. The television programme pointed out, correctly, that HIV is not a legitimate target for inhibition with a chain terminator of DNA synthesis in people with antibodies against HIV. No study has detected HIV DNA synthesis from viral DNA, and virtually none has found free HIV in such people, because antiviral immunity effectively inhibits HIV replication to undetectable levels.l This is why it is notoriously difficult to isolate HIV from AID S patients. In antibody-positive individuals AZT can only inhibit that HIV proviral DNA which is already integrated into cell DNA; in other words it has to kill the cell to inhibit HIV. Since only 1 in 500 T-cells contains HIV DNA, AZT must kill 500 uninfected cells to kill just HIV-infected cell.2 Several studies demonstrate the resulting toxicity of AZTOne of these, published in The Lancet, demonstrated that 10 of 11 AIDS patients recovered cellular immunity on discontinuing AZT in one

seropositivity in paid blood donors

SiR,—European Community directive 89/381 demands "the production and use of products derived from human blood or human plasma coming from voluntary unpaid donations". Whether the implementation of this requirement will improve the safety of blood supplies in Europe is still being debated. Since in other European countries information about the impact of paying donors on blood product safety is scarce, data from Germany may be of interest. Over 6 million randomly selected blood and plasma donations, collected in different regions of former West Germany between 1985 and 1991, show the following picture:

1. Doglio G, Pusajo J, Egurrola M, et al. Gastric mucosal pH as a prognostic index of mortality in critically ill patients. Crit Care Med 1991; 19: 1037-40. 2. Maynard ND, Bihari D, Mason R, et al. A comparison between gastric intramucosal pH and pulmonary artery oxygen transport measurements on the ITU. Br J Surg 3. Keene AR, Cullen DJ. Therapeutic Intervention Care Med 1983; 11: 1-3.

PETER H. DUESBERG

CI)

(n=1447 290J

Unpaid donations (n 4670 257)

222 15-34

90 1-93 8-0

=

(6-2-10-2)

These figures suggest that with remunerated donations measures aimed at eliminating at-risk donors before laboratory screening are not

effective enough.

Red Cross Blood Donation Service, 4400 Munster, Germany

H. FIEDLER

Exposure to chemicals and development of malignant disease SiR,-Your Feb 1 editorial about a possible association of brain gliomas and industrial or hospital laboratory chemical exposure has important implications for further epidemiological research and industrial practice. We report two cases of malignant gliomas in fairly young patients who had prolonged exposure to volatile reactive organic compounds in the chemical industry. Both patients were non-smokers and no other potential cause of malignant disease could be identified. Patient 1-A 41-year-old man presented with paraesthesiae of the right fingertips followed by a progressive right hemiparesis. Computed tomography (CT) revealed a left frontoparietal tumour, which was histologically grade III-IV astrocytoma. The patient had worked for 25 years in the chemical industry and had been exposed to chemicals used in the production of vinylidene chloride and other solvents. Patient 2-A 43-year-old man presented with frontal headaches, nausea, tremor, and difficulty with fine movements of the right hand. CT revealed a large left frontoparietal tumour, which proved to be a glioblastoma multiforme on histology. The patient had been closely involved in the development of paraquat production with exposure to agents such as 4,4’ bipyridyl. We are also concerned about the pattern of registration for brain tumours reported by the Mersey Cancer Registry (1983-87). The standardised registration ratios (SRRs) for all health districts in the Mersey region were calculated with the England and Wales cancer

552

statistics (1985)2 as the standard reference. SRRs of 173 (Halton), 152 (Wirral), and 146 (Chester) were found for male subjects at all ages. Lower ratios were seen in all other districts. There is a concentration of petrochemical industrial plants along the upper Mersey estuary, especially around Halton, and these are encircled by these health districts. Slightly lower ratios were found for some other districts that include chemical industries-123 (Macclesfield) and 133 (Warrington). Organic chemicals with high partition coefficients can probably be absorbed by inhalation or ingestion and cross the blood-brain barrier. Those with critical chemical structures may induce malignant disease by interaction with DNA. Highly lipid-soluble

cytotoxic drugs (eg, carmustine, lomustine, procarbazine)

are

absorbed via the gastrointestinal tract, cross the blood-brain barrier, and are active in the treatment of malignant gliomas. Similar mechanisms may be involved in the induction of malignant cerebral tumours.

Mersey Regional Centre for Radiotherapy and Oncology, Clatterbndge Hospital, Bebington, Merseyside L63 4JY,

BLEDDYN JONES UK

CAROL BLEASDALE

Youngsen JH, Ashby D, Hussey RM. Cancer in Mersey: incidence of cancer in Mersey region and its constituent health districts 1983-1987. Liverpool: Mersey Cancer Registry, Mersey Regional Health Authority, Liverpool, 1991. 2. Office of Population Censuses and Surveys. Cancer statistics registration 1985. London: HM Stationery Office, 1990. 1.

Infection after subcutaneous interleukin-2 SIR,-Dr Jones and colleagues (Jan 18, p 181) report a high frequency of bacteriologically proven infection in patients receiving subcutaneous interleukin-2 (IL-2) and interferon-ot (IFNa), which they attribute to IL-2 treatment. They advise careful monitoring of treatment with subcutaneous IL-2, and the investigation of the role of prophylactic antibiotics in this context. We have reported an outpatient regimen with subcutaneous IL-2 in patients with disseminated renal-cell cancer.1 In short, patients received daily subcutaneous injections of 18 x 106 IU IL-2 (EuroCetus, Amsterdam, Netherlands) on days 1-5 in the first week, the dose in the first 2 days of the following weeks being reduced to 9 x 106 IU. Up to January, 1992, 24 men and 18 women (mean age 59 years, range 29-76) received 468 weeks of treatment. We found clinical evidence of infection for which antibiotics were indicated on six occasions (1 3%). 1 patient with a spinal cord lesion and atonic bladder was treated three times for recurrent urinary infections that were related to the urinary catheter. A second patient received antibiotics for a local infection with group B haemolytic streptococci in the leg that was compromised with a thrombotic venous occlusion. 1 patient with multiple lung metastases received treatment for a clinical pulmonary infection, and 1 was treated for a clinical epididymitis. Although routine blood cultures were not done and symptomless bacteraemia cannot be excluded, the low incidence of clinical infection in this group of 42 patients and the absence of symptoms that could be ascribed to bacteraemia suggest that there is no indication for the use of prophylactic antibiotics in patients treated with subcutaneous IL-2 alone. Since no excess of infection in cancer patients receiving IFNa has been reported,2,3 the relation between combination therapy with IL-2 and IFNoc and infection needs further investigation.

J. BUTER Department of Medical Oncology, University Hospital, 9713 EZ Groningen, Netherlands 1.

E. G. E. DE VRIES D. TH. SLEIJFER P. H. B. WILLEMSE N. H. MULDER

Sleijfer DTh, Janssen RAJ, Willemse PHB, et al. Low-dose regimen of interleukin-2

for metastatic renal carcinoma. Lancet 1990; 335: 1522-23. 2. Muss HB. Interferon therapy for renal cell carcinoma. Sem Oncol 1987; 14 (suppl 2): 36-42. 3. Creagan ET, Twito DI, et al. A randomized prospective assessment of recombinant leucocyte A human interferon with or without aspirin in advanced renal adenocarcinoma. J Clin Oncol 1991; 9: 2104-09.

Hypersensitivity to Samsum ant SiR,—Insect sting allergy is usually associated with bees and Among the ants only the more primitive subfamilies have

wasps.

retained their sting.1 Allergic reactions to the sting of the fire ant (Solenopsis invicta and S richteri) are a well-recognised hazard in much of North America.2 Pachycondyla sennaarensis (Mayr), known locally as the "Samsum ant", is widely distributed in the Arabian Peninsula. This small black ant is notorious for its painful sting. We report that the sting of this ant can result in severe anaphylaxis. The only ants previously known to cause IgEmediated allegy belong to the genera Solenopsis and Pogonomyrmex (harvester ants), both in the myrrnicinae subfarnily.3,4 During the period November, 1987, to March 1990,40 patients with generalised reactions to the sting of the Samsum ant were evaluated in the allergy clinic, Tawam Hospital. Some were brought directly to the emergency room and others were referred from elsewhere in the United Arab Emirates. Both groups were seen again later in the allergy clinic for questionnaire and allergy evaluation. Thus, information on signs and symptoms were based mainly on records, whereas information on the time of onset of reactions, history, previous reactions, and so on was provided by the patients in the clinic. Most patients were skin-prick tested with fire ant (S invicta) whole-body extract and a range of common allergens, and a radioallergosorbent test (RAST) was done against these allergens in a reference laboratory. Total serum IgE was measured by radioimmunoassay. We also questioned 40 people who had been stung by the Samsum ant but who had no systemic reaction. Most patients described the ant accurately and some brought specimens to the clinic. Other specimens were sent to the British Museum (Natural History) in London where they were identified as P sennaarensis (Mayr). Most patients were young women with a history of allergy and about half had had four or more generalised rections to the ant sting: No

-

11/29

M/F 32

Mean age (range) History of "allergy"*

(13-64) yr 29

History of anaphylactic reactions to ant sting 3 times 4 times Time of onset of symptoms < 15 min 15-60 min 1-3 h Not known *Mainly asthma and/or allergic rhinitis and/or conjunctivitis. < >

18 22 24 8 5 3

The most common symptoms involved the respiratory system and the skin:

Sign/symptom Respiratory Wheezing Dyspnoea Spasmodic cough without wheezing Laryngeal oedema Laryngeal pruritis without oedema Hoarseness Skin Generalised oedema Generalised urticaria

No

Sign/symptom

No

Gastrointestinal 27 31 5 12

6 5

Vomiting, nausea Abdominal pain Pharyngeal oedema

Neurological Syncope Headache Other

Fatigue/malaise Rhinitis

22 27

Conjunctivitis Chills

3 3 4 5 6 13 12 9 3

We know of 2 other people, known to be allergic to the Samsum ant, who died after its sting; another woman went into coma, with sequelae on recovery; and a 32-year-old woman went into anaphylactic shock after a sting from this ant. 18 of 35 patients tested had skin reactivity and 10 of 36 had specific IgE antibodies to fire ant allergens. 73% (27/37) had total IgE levels above the upper limit of normal for the reference

laboratory (180 IU/mi). As far as we are aware, this is the first report of hypersensitivity reactions to the sting of the Samsum ant. This species is widely distributed in the Arabian Peninsula and in tropical Africa (B. Bolton, personal communication), so it is likely that hypersensitivity reactions do occur elsewhere. Our series suggests that atopic

Exposure to chemicals and development of malignant disease.

551 ICU OUTCOMEAND MEAN DA!LYT!SSATGUY’SHOSP!TAL, 1991 In our unit, only when TISS is more than 40 points do we see such a mortality rate (table). M...
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