1036 The "real false-positive". Either the media are not able to sustain growth with few organisms not visible by z.N., or the organisms seen with auramine are artefacts.


SIR,-Dr Hoo’ says that deletion of the short arm of the human X chromosome not involving segment b of his figure (corresponding to Xpll of the Paris Nomenclature) does not cause any clinical symptoms. From this he concludes that segment a (corresponding to Xp2 and part of Xpl) is present fourfold in the female. He cites a case reported on at the meeting of the German Cytogenetical Society2 with a short-arm deletion at band pll in a mother and daughter, both of whom apparently were without any clinical manifestations. Dr Hoo seems to be unaware of a case published by Boczkowski and Mikkelsen3 with a similar X short-arm deletion at band pll, who showed signs of Turner’s syndrome, including primary amenorrhcea, short stature, and webbing of the neck. It follows that segment a may not be present four-fold, as Dr Hoo suggests, and therefore that his theory of sex-chromosome evolution may not be correct. Institute of Genetics, Basle University Children’s Hospital, CH-4000 Basle, Switzerland.

carefully at the morphology In our experience, some of these particles. found when blood is have been auramine stains false-positive The in the morphology of these fluorescent present sputum. particles is sometimes difficult to evaluate. Some of them are platelets (which stain with auramine). If there is gross contamination with blood, there is no problem in identifying the probable cause of the false-positive smear. If there is occult blood in the sputum, there is the possibility of false-positive auramine stain, and the z.N. will be negative. We are now investigating the auramine staining of artificially platelet-contaminated sputum in order to evaluate the extent of the falsepositive auramine staining. Also, we use it to train technicians to look more carefully at the morphology of the fluorescent In the last case, of the fluorescent

should look

particles. Brown

University, Hospital,


Pawtucket, Rhode Island 02860,








Dr Weinstein and his

colleagues say (July 26, 173), "ongoing analysis" of sputum specimens is essential for early detection of smears false-positive for mycobacteria. False-positive smears are smear-positive, culture-negative spe-

are concerned about the implications of your edi(Sept. 27, p. 593), suggesting that tuberculosis is now disappearing to such an extent that one can afford to be complacent. The reasons for abandoning the routine tuberculin testing of 13-year-old schoolchildren and giving B.c.G. are, firstly, that an insignificant number of children are picked up




cimens. One

must distinguish between the false-positive due to laboratory contamination and the smears that Dr Mitchison and her colleagues (Aug. 9, p. 281) call the "genuine falsepositive", where no reasons are found for failure of growth after a positive smear. The interpretation by the clinician of these positive smears is extremely difficult. This is even more important with auramine staining of sputum,’ which is easier to perform and read and more sensitive than the Ziehl-Neelsen (z.N.). Does the finding of a positive auramine stain alone, in patients not on chemotherapy, warrant starting antituberculous therapy without waiting for the results of the culture? More data on the follow-up of patients with positive smears only should be made available. The decision to treat or not to treat has to be made at the time of the smear. Retrospective

studies, which include the results of the cultures, have


with tuberculous infection relative to the expense and work involved, and, secondly, that the incidence of tuberculosis is now so low that there is no need to protect the population, Tuberculosis has definitely not disappeared. Amongst 13-year-olds Heaf-tested in North Hampshire in the past two academic years, 47 were found to have strongly positive reactions ; and, of these, 4 had active tuberculosis. 2 of the children had primary infections which had ulcerated into the bronchial wall and were therefore infectious. As these 4 all came from different comprehensive schools, with the number of pupils varying from 1087 to 1435, this involved a large amount of additional screening with serious public-health implications. In the past year, from the town of Alton (population 13 800), there have been 23 cases of tuberculosis notified. 13 of these were from the same source; 3 adults had active tuberculosis; 10 children were found to have primary infections, and 7 of these are now receiving treatment. Of the further 10 additional cases, only 2 men who work in the same business have had any known contact with each other. Amongst the 5 children in this group, 2 have extrapulmonary infections; and, among the children in Alton receiving treatment, 6 are 6 years of age or younger. We are not convinced that tuberculosis has been conquered, and we cannot therefore, afford to be complacent about this potentially serious disease. J. C. BOWE Basingstoke District Hospital, J. M. DARMADY Park Prewett, T. E. ROBERTS Basingstoke, P. TOMLINSON Hants RG24 9NA


far as treatment is concerned. This laboratory follows the procedures of the Communicable Disease Center, Atlanta, Georgia. The sputum is stained with auramine, and only the positives are stained with Z.N. All specimens are cultured. In three years, 4669 specimens have been processed. The positives results can be classified in five as



Category 1.-Stain-negative, culture-positive. This is why cultures done. Specimens are negative to both stains, probably because there are too few mycobacteria to be picked up. Category 2.-All positive. Enough bacteria to be picked up by both are




Category 3.-Auramine-positive, z.N.-negative, with a positive culDemonstrates the advantage of the auramine stain. Category 4.--Positive with both stains, culture negative. Either the bacteria were not viable or the media were inadequate to support their growth. Culture media do not sustain growth as well as the lungs do. Category 5.-Auramine-positive, z.N.-neganve, culture-negative.


1. Hoo, J.-J. Lancet, 1975, i, 1299. 2. Van den Berghe, H. Meeting of the German Cytogenetical Society Berlin, 1974. 3. Boczkowski, K., Mikkelsen, M. J. med. Genet. 1973, 10, 350. 4 Bennedsen, J, Larsen, S. O. Scand. J. resp. Dis. 1966, 47, 114.


SIR,-How should corticosteroids be withdrawn from a patient maintained on them? You say in your editorial (Sept. 20, p. 537) that 1 mg prednisone or its equivalent should be withdrawn about every three days. Dr Bloom (Oct. 4, p. 659) thinks this is too quick; and Grant’ would withdraw only 1 mg per month. Naturally, withdrawal should be gradual, since we assume 1. Grant, I. W. B. Prescribers

J. 1975, 15, 46.

1037 that the adrenal cortex has suffered a loss of function or even some atrophy. This change will be the greater, the longer the previous corticosteroid treatment has been given and the higher the maintenance dose. Therefore the loss of function in each case will differ widely and the method of withdrawal must be adapted to it accordingly. Thus, there cannot be any hardand-fast rule about the speed of withdrawal, as suggested by the authors I have cited. If I, for instance, prescribe prednisone in severe asthma, I start with 30 or 25 mg/day for five to seven days. If successful, the dose is reduced by 5 mg/day every five days until 15 mg/day is reached; then by 2.5 mg/day every seven days until 10 mg is reached, and then by 1.25 mg/day every week. During this descent either the maintenance dose is found or the drug can be withdrawn completely. I have not seen a single case of withdrawal symptoms during the past twenty years and in what must be over 1000 patients. However, the rate of withdrawal may be much slower if the starting doses are higher, as in some malignant conditions, or in rheumatoid arthritis, where the higher daily doses may have to be given for longer periods. 9 Park Crescent, London N3 2NL.



SIR,-We read with interest the report by Dr Toivanen and others (Aug. 2, p. 205) contrasting their results with those of Davies et al.1 on the significance of raised titres of antibodies against milk proteins in patients with myocardial infarction. Though it seems from these investigations that such antibody titres bear little relation to the aetiology of myocardial infarction and the pathogenesis of coronary heart-disease, it would indeed be premature to discount the possible role of bovinemilk consumption in atherogenesis. Perhaps a crude analogy might illustrate what we mean. A clinically asymptomatic luetic patient is known to have a positive v.D.R.L. or Wassermann test. These immunological indicators of latent treponema infection do not anatomically identify the luetic lesion. Similarly, the existence of circulatory bovine-milk-prbtein antibodies can indicate the intraorganismal presence of atherosclerotic lesions without pin-pointing their sites (peri-

pheral arteries, aorta, or coronary arteries). The mere presence of such antibodies in a large patient population certainly suggests the intestinal absorption of large intact and undigested protein molecules, and suggests that more attention should be directed to the detection by sensitive techniques of more specific bovine-milk-protein antibodies. Our laboratory has shown a much better correlation between the presence of atherosclerotic disease processes and the titre of antibodies to bovine-milk xanthine oxidase.2 We were able to confirm the work of Davies et al., using his method and also employing dried whole-milk antigen. A total of 75 cases, including controls, were tested for 75 degrees of freedom. The antibody-to-milk protein test had an independent t value of 2.89, and Davies et al., with 48 degrees of freedom in 50 cases, obtained a t value of 2.85. However, the antibodies to electrophoretically pure bovine xanthine oxidase had an independent t value of 4.86 (p < 0.001) in the sera of the same group of patients, which is extremely significant. Accordingly, we strongly recommend greater investigative discrimination between specific bovine-milk antibodies rather than the crude estimation of "milk antibodies," a non-specific category which generates a pot pourri of non-significant immune responses between patient and control group, as reported by Toivanen et al. and Davies et al. A more refined sample selection between a milk-consuming and a non-bovine-milk-consuming population control group, such as Central American Indians or 1. Davies, D. F., Davies, J. R., Richards, M. A. J. Atheroscler. Res. 1969, 9, 103. 2. Oster, K. A., Oster,

J. B., Ross, D. J. Am. Lab. August, 1974.

Blacks with lactose intolerance, would serve to emphasise the impact of dietary differences on atherogenesis. Department of Biology, Fairfield University, Fairfield, Connecticut 06430, U.S.A.



SIR,-Dr Thacker (Oct. 18, p. 770) has provided a very useful and cogent response to Dr Galperin-Lemaitre and his colleagues (Oct. 4, p. 662) by questioning the latters’ contention that ultrasound properly employed for diagnostic purposes might have a mutagenic effect on cellular D.N.A. Dr Thacker marshalled the recent experimental evidence refuting this suggestion, he pointed out that appropriate use of the term "mutagenic" involves effects upon progeny, and that where stresses are sufficiently high to damage cellular D.N.A. these stresses are likely to cause cell disruption and death without genetic involvement. We wish to support Dr Thacker’s views by emphasising the great difference in molecular conformation, and the consequent mechanical force interactions possible, between the cellular (chromosomal) D.N.A.-protein nucleohistone complex and D.N.A.-salt in aqueous solution. The former exists in a tightly coiled conformation and has greatly restricted access for contact with neighbouring molecular species. Conversely D.N.A. in aqueous solution is free to elongate when stressed and is in intimate chemically related contact with the solvent molecules. Polymers exposed to ultrasound of a sufficiently high intensity are degraded to a )i" ’"_1 - no!ecular weight,’ implying that the mechanical stresses involved require a minimum molecular length before being capable of disrupting the polymer. Other forms of radiation can interact irreversibly with D.N.A. at point locations. We suggest, therefore that, other forms of radiation notwithstanding, the application of the mechanical forces delivered to macromolecules via ultrasonic waves are such that extraordinary caution must be exercised in extrapolating results of studies of solutions to in-vivo consequences. When biopolymer degradation occurs at the intensities (200 mW/cm2) quoted by Dr Galperin-Lemaitre and his colleagues the effect can usually be shown to arise from the stress set up about excited gas bubbles (cavitation) in the sample. The quoted intensity is at the lower end of the wide range of intensities reported as cavitation thresholds at 1 MHz.23 When cavitation occurs at such low intensities it is usually found that reflections from the rear of the treatment assembly produce a quasi-standing wave field which traps bubbles of different size ranges at pressure antinodes or nodes and affords them an opportunity to grow in the sound field to a size at which they can damage macromolecules or cells in the medium. The work of Dr Galperin-Lemaitre and his associates is of interest therefore in drawing attention again to the fact that cavitation can arise in water at intensities used in clinical practice. The conditions under which cavitation can occur in tissues have not been well defined. It is probable that quasi-standing waves are produced in the body when continuous ultrasound is used in therapy and in diagnosis (not with pulse-echo techniques, as in ultrasonic scanning). Any damage to cells which would arise if cavitation occurred in the less structured (homogeneous) liquid anatomical regions would be undesirable, even though we need not expect it to be genetic. When reporting some years ago that blood stasis could be produced in a quasi-stationarywave situation in ultrasonically treated chick embryo. Dr Dyson and her colleagues4 suggested that, where possible, movement of the transducer head during clinical application of continuous ultrasound would lessen the chance of the build up 1. Gooberman, G. J. Polymer Sci. 1960, 42, 35. 2. Barger, J. E. Thresholds of Acoustic Cavitation. Technical Report no 57, Acoustics Research Laboratory, Harvard University, Cambridge, Massachusetts, 1964. 3. Iernetti, G. Acustica, 1971, 24, 191. 4. Dyson, M., Woodward, B., Pond, J. B. Nature, 1971, 232, 572

Letter: Withdrawal of corticosteroids.

1036 The "real false-positive". Either the media are not able to sustain growth with few organisms not visible by z.N., or the organisms seen with aur...
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