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demonstrate a late response only. Lee and associates failed toappreciate this important point-namely, that our group of isolatedlate responders gave negative skin prick test responses to therelevant allergen, possessed only allergen-specific IgG4 antibodiesin their sera, and were only identified as a result of screening the seraof a large group of atopic subjects. 2These differences in approach to the selection of patients could

possibly explain why patients 7, 10, 11, and 12 in the study of Lee etal. gave dual reactions in the apparent absence of circulating IgG4antibody. Alternatively, this could be due to the adoption of adifferent criterion for the presence or absence of allergen-specificantibodies of this IgG subclass in the patients’ sera. We

compared our RAST results with the mean value obtained fromanalysis of the sera of thirty normal (non-allergic) individuals,considering any test serum value which was 2SD above this mean tobe raised significantly. Lee et al. related their test serum RASTbinding value to that of a positive ’references serum, apparentlyassigned an arbitrary value of 100 U/ml of IgG4 antibody which wasdirected against an irrelevant allergen (milk). The basis on whichthis particular serum was selected as reference for sera containingIgG4 antibodies of other specificities, and the reason for considering atest value greater than 20% in relation to this as significantly raised,is not stated. Hence, it is possible that one laboratory is being morestringent than the other in deciding what RAST value correspondsto a raised serum IgG4 level. For instance, if one takes the limit ofpositivity of the RAST values of Lee et al. as 5 U/ml, theirimmunological findings on patients 4-13 inclusive are not

inconsistent with our findings. ,2Lee et al. claimed that we used only one control but we clearly

stated that we did control provocation tests on two of us (one ofwhom, T. A., was allergic to a non-test allergen) and on an intrinsicasthma patient. We also indicated that the patients were challengedwith full-strength control solution, thus acting as their owncontrols. We made no mention of medication at the time of

challenge since we assumed that it would be taken for granted thatwe would not have done provocation testing without stopping alldrugs for at least 24 h before challenge.

Lee and associates did not indicate whether any of their grass-pollen-sensitive patients had previously undergone hypo-sensitisation. We avoided including any such patients in our

study because there is some evidence that IgG4 antibodies to grasspollens produced as a result of such treatment may not behave in thesame way as those found in the circulation of non-hyposensitisedhayfever patients.We suggest that there is scope for further bronchial provocation

testing and other clinical studies (preferably by other laboratories,too), before IgG4 antibodies are dismissed as being "unlikely to playan important role in allergic disease".

Rheumatology and Allergy Research Unit,Department of Immunology,Medical School,University of Birmingham,Birmingham B15 2TJ

C. M. GWYNNT. ALMOSAWID. R. STANWORTH

URINE SPECIFIC GRAVITY TEST STRIPS

SIR,-I would like to comment on the letter from Dr Robson andcolleagues (Nov. 20, p. 1164). We too have evaluated the newreagent strip ’N-Multistix SG’.3 We tried to draw attention to thefact that evaluation of simple ward tests of this sort should recognisethat the clinician is searching for a broad classification for hispatient and that he is unlikely to (and should not) place the sameemphasis on this as he might place on a physiological measurementof urine osmolality. To compare the two techniques by a correlationcoefficient is an oversimplification. We have taken particularinterest in patients whose results do not correlate when two or moreof the traditional methods of assessing concentration are contrastedwith the new Ames test strip.

2. Gwynn CM, Almosawi T, Stanworth DR. Clinical associations with serum allergen-specific IgG4 antibodies. Clin Allergy 1982; 12: 459-64.

3. Frew AJ, McEwan J, Bell G, Heath M, Knapp MS. Estimation of urine specific gravityand osmolality using a simple reagent strip. Br Med J 1982; 285: 1168.

Unlike Robson and colleagues I would encourage the use of thisnew strip, cautiously at this stage. We plan to publish our analysis ofpatients in whom there has been a discrepancy between a

conventional measurement of concentration and the N-multistixSG result. If others keep a careful note of patients in whom there issuch a discrepancy the correct role for this new method may emerge.Until then I suggest that an assesment of urine concentration by thismethod is much better than no measurement of urine concentration atall in a case where such information helps clinical decision making.Tests should not be used in isolation to make major decisions, and

caution is always necessary when a new method is introduced. Isuspect that most of the concern expressed by Robson andcolleagues is based on the implied correlation between specificgravity and the result of the new test. The manufacturer’s literatureshows that something very different from the weight of dissolvedsolids is being measured: the test is a guide to what the specificgravity may be, not a measure of it. There are situations wherespecific gravity is not a good measure of urine concentration, and Iagree that urine osmolality must be measured when a veryimportant clinical decision has to be made.10 1 Lambley Lane,Burton Joyce,Nottingham NG 14 5BL MARTIN S. KNAPP

PROPRANOLOL AND ARTERIAL AMMONIA IN LIVERCIRRHOSIS

SIR,-We read with interest the article on the effect of propranololon arterial ammonia concentrations in liver cirrhosis by Dr vanBuuren and colleagues (Oct. 30, p. 951). Four of their six patientswith cirrhosis had raised basal arterial ammonia levels. In two of

these, ammonia levels rose after 3 days’ treatment with propranololand then started to fall after 6 days of treatment; the level in oneother patient rose during propranolol treatment to reach a peak 3days after the drug was stopped; the fourth patient’s arterial bloodammonia did not change. They further illustrate two cirrhoticpatients with normal basal arterial ammonia levels in whom theconcentration rose with propranolol therapy and three other

patients with fatty infiltration whose ammonia levels appeared tofall with therapy.These are small numbers on which to attempt to analyse the

altered pharmacodynamic effects of propranolol on arterialammonia levels, and the results are difficult to interpret. It is

unjustified to assert that the rise in ammonia levels of similarproportions in the patients with normal basal levels "arguesagainst" the proposal that saturation of an overloaded uptakemechanism by reduced hepatic blood flow could account for thechange. Ammonia levels do not accurately follow the degree ofhepatic damage and can be affected by many factors other thansolely hepatic function (diet, intestinal bleeding, bacterial floral).Normal basal levels therefore do not imply that an uptake system isnot operating at a saturated level.Two of the three patients with fatty infiltration had significant

hypoalbuminaemia, which suggests at least a moderate degree ofabnormal hepatocellular function, yet these patients had no rise inthe arterial ammonia levels during beta blockade. The cirrhoticpatients used in this study represent patients with severe liverdisease (four had persistent ascites despite diuretic therapy, threehad serum albumin levels less than 30 g/1, and one had a serumbilirubin of 298 j1molll). Patient 3, without ascites or oesophagealvarices, showed no significant change in arterial ammonia levelswith propranolol therapy. This patient, the only cirrhotic patient inwhom the arterial ammonia did not rise, was also the only patient tobe taking an antibiotic known to affect the intestinal bacteria florainvolved in the synthesis of ammonia. 1The average age of the patients with fatty infiltration was only 44,

compared with the average for the cirrhotic group, which was 65.Hence, comparisons between these two groups must be made withcare.

Department of Medicine,Ninewells Hospital and Medical School,Dundee DDI 9SY

P. C. HAYESA. N. SHEPHERD

1. Sherlock S. Disease of the liver and biliary system, 6th ed. Oxford: Blackwell ScientificPublications, 1981 chap. 8.