- Email: [email protected]
THE CONTROL OF VENEREAL DISEASE
441 I suggest the
answer is simple-even if its implicadisturbing. Perhaps rheumatoid arthritis is not a complaint-a disorder. Perhaps it is a way by which a patient intimates, in pathological terms, that he is complaining. He may, of course, be disposed by heredity to rheumatism rather than to other complaints; or he may have some constitutional
Why ?
tions
are
occupational bias towards it. But the actual emergence of the symptoms may represent the psyche’s cry for help. Suggestion, it has now often been shown, is capable of answering that cry as effectively as drugs. But how much attention is currently being given to research into how to employ it more
or
effectively ? BRIAN INGLIS.
London W.2.
OSMOMETRY SIR,-Dr. Dormandy, in his interesting Occasional Survey (Feb. 4, p. 267), points out the theoretical objections to the measurement of osmolality by cryoscopic methods. He also stresses the advantages of thinking in terms of vapour pressure when considering osmolality. We have not had any experience with cryoscopic methods but agree with Dr. Dormandy that, whatever the theoretical objections, they are satisfactory for most clinical purposes if they give a satisfactory degree of accuracy for the particular problem being studied. In recent experiments we have been able to measure osmolality using a’Mechrolab ’ 301A osmometer which Professor H. S. Heller (department of pharmacology, Bristol University) has CHANGES IN PLASMA-OSMOLALITY, URINE-OSMOLALITY, AND URINEFLOW RATES IN TWO NORMAL SUBJECTS GIVEN A WATER-LOAD AT 8.30 A.M.
Plasma-samples taken
at start
of each period.
generously made available. This instrument does, in fact, directly the vapour pressure of the solution. We still express our results in mosmoles per kg., based on a calibration curve obtained using standard sodium-chloride solutions. With this instrument it is possible to obtain consistent results in the range of 250-320 mosmoles per kg. with 95% confidence limits of less than 4 mosmoles per kg. After the initial calibration each estimation takes 21/2 minutes. Using this instrument, we have obtained results which conflict with some of the conclusions reached by Dr. Dormandy and his colleagues in their preliminary communication (Feb. 4, p. 246) on the constancy of plasma-osmolality. Our results are very similar to those obtained by Baldes and Smirk, White and Findley,2 and other workers quoted by Homer Smith3 in studies of plasma during water-loading experiments. In the accompanying table are the changes observed in two normal subjects after oral ingestion of a water-load (18 ml. per kg. body-weight) at 8.30 A.M. This water-load, which is similar to that used by Dr. Dormandy and his colleagues in their volunteers, can be seen to produce a fall in plasma-osmolality which precedes the onset of the diuresis. Following the excre-
measure
1. Baldes, E. J., Smirk, F. H. J. Physiol., Lond. 1934, 82, 62. 2. White, H. L., Findley, T. Am. J. Physiol. 1937, 119, 740. 3. Homer Smith, W. The Kidney. London, 1951.
tion of a large amount of hypotonic urine, the plasma-osmolality can be seen to be returning towards basal levels. These findings correspond to those of the other authors cited and provide evidence for the small shifts in plasma-osmolality which precede water diuresis and which Dr. Dormandy suggests must occur but which he did not detect in his experiments. The alteration in plasma-osmolality which was observed is greater than the 1 % change which Verney4 demonstrated was necessary to produce antidiuresis in dogs when he perfused their carotid arteries with slightly hypertonic saline solutions. It seems most likely that the fall in osmolality which we have observed inhibits the secretion of antidiuretic hormone and the delay between this fall and the onset and peak of diuresis is attributable to the duration of action of antidiuretic hormone. This does not, of course, exclude the possibility that active renal excretion of water may occur either because of the reduced secretion of antidiuretic hormone or from some direct effect of the drop in plasma-osmolality on the kidney. We will await the results of further experiments and also the publication in more detail of those presented in the preliminary communication of Dr. Dormandy and his colleagues before accepting that active excretion of water by the kidney tubule does occur. MARTIN S. KNAPP PAUL M. KEANE. Bristol Royal Infirmary.
THE CONTROL OF VENEREAL DISEASE SIR,-A far greater problem in the control of the spread of venereal disease than the female contact who, having been traced, refuses to cooperate are those who cannot be traced at all. In this clinic, during a period of twelve months, 39-85% of the female contacts of the men attending with gonorrhoea were traced and attended either here or elsewhere, 60.15% could not be traced, and only 0-73% were traced and refused to attend. Failure to trace the contact was almost always due to genuine lack of information of sufficient personal details. Contact tracing is essential and valuable but can do nothing to reach this large group of unidentifiable women, and this aspect of the problem needs continuing study and a different line of approach. There are several reasons why women do not attend a clinic of their own accord. The most obvious one is the absence of symptoms in uncomplicated gonorrhoea in the female. Equally important factors are that women appear to have a less realistic attitude than men to the risks of casual encounters, and are more frightened at the idea of attending a clinic. Unfortunately many members of the medical profession are also slow to appreciate the need for special investigations in women who have been at risk, and at times seem to reflect their patients’ dislike and distrust of the " special clinic ". Women should be referred for examination and should be encouraged to request examination whenever they have been at risk. Doctors should also encourage their patients to regard the special clinics, not as places to be visited only in the last resort, but as ordinary outpatient departments offering a useful service in the diagnosis of all types of genital infections as well as in the treatment of venereal disease. In this connection, much more use could be made of routine screening procedures-e.g., on patients attending antenatal clinics. To reintroduce compulsory powers over " persons suspected of having venereal disease " would have a very damaging effect on progress along these lines, and would undo much of the good work which has been done in recent years in improving the standard of clinics and the relationship between venereologists and their colleagues in other branches of medicine. My personal objections to the idea of forcibly examining patients are so strong that I would not be associated with any such procedures, but I shall not enlarge on the moral aspects which have been admirably dealt with by previous correspondents. The point I wish to emphasise is that, in my view, the number of patients who would be frightened away 4. Verney, E. B. Proc. R. Soc. 1947,
135,
25.
442 from the clinics if powers of compulsion were employed would far exceed the numbers of those forced to accept examination and treatment by these means. Department of Venereology, King’s College Hospital, EVA GALLAGHER. London S.E.5.
DIPHTHEROIDS AND RHEUMATOID ARTHRITIS SiR,ŃThe preliminary communication by Dr. Duthie and his co-workers (Jan. 21, p. 142) certainly justifies further
investigation. tion between diseases.
This work recalls
Medical Rehabilitation Centre, 152 Camden Road, London N.W.1.
TESTING FOR HYPOPARATHYROIDISM SIR,-In 1963Iexpressed doubt whether partial hypoparathyroidism (defined as impaired response to a calciumdeprivation test in patients with normal serum-calcium levels) could cause symptoms, and hoped that Dr. (now Prof.) P. Fourman’s group would carry out a double-blind trial on their patients with this condition. This they had already embarked on,2 but no results have yet appeared. Dr. Stowers and his colleagues (Jan. 21, p. 124) have now tried to fill this gap in our knowledge with a double-blind crossover trial of calcium gluconate in patients with partial hypoparathyroidism identified by trisodium-edetate (T.S.E.) infusion,3 from whi@h they conclude that these patients’ symptoms were unrelated to their defect in parathyroid function. It should be gratifying to find my prediction confirmed, but unfortunately their work is open to the serious objection that the dose of calcium gluconate used was far too small. Fourman et a1.2 reported on the results of treatment (uncontrolled) in a series of 46 patients with different degrees of parathyroid insufficiency. 12 of these patients, identified by either sodium-phytate loading4 or T.s.E. infusion,3 had an initial serum-calcium level of 8-50 mg. per 100 ml. or greater, and were treated with calcium alone in doses of 3-4 g. daily. It was claimed that 5 of these patients, whose mean serum-calcium levels increased by 0-52 mg. per 100 ml. (from 8-98 to 9-50 mg. per 100 ml.) had partial relief of symptoms, and that the remaining 7, whose mean serum-calcium levels increased by 0-76 mg. per 100 ml. (from 9.12 to 9-88 mg. per 100 ml.), had complete relief of symptoms. Clearly, to rebut the claim that a rise in serum-calcium level of this order can lead to symptomatic improvement, it is necessary to give sufficient calcium to the subjects of a double-blind trial to produce such a rise, or to prove that such a rise cannot be achieved by 3-4 g. of calcium daily. Since Dr. Stowers and his colleagues gave their patients only 0-72 g. of calcium daily, and did not achieve any rise in serum-calcium levels, no symptomatic improvement was to be expected, regardless of the nature of their patients’ symptoms. Rosegave her patients 3 g. of calcium daily, but unfortunately none of them had partial hypoparathyroidism as defined above, although the fact that they had the same symptoms tends to discredit the relationship of such symptoms to impaired parathyroid function. I remain sceptical of the claim that so small a rise in serumcalcium level can be of so great therapeutic benefit, but it is still unrefuted seven years after the concept of partial hypoparathyroidism was revived.4 Even if the results of their trial were accepted, the conclusion by Dr. Stowers and his colleagues that partial hypoparathyroidism has no clinical reality would be unjustified. An impaired response to calcium deprivation, even if it does not cause symptoms or require treatment, probably indicates decreased parathyroid function, and such patients should surely be kept under observation in case they develop convulsions many years later.6-8 Medical Professorial Unit, University of Queensland, Brisbane Hospital, A. M. PARFITT. Brisbane, Australia. 1. Parfitt, A. M. Lancet, 1963, ii, 465. 2. Fourman, P., Davis, R. H., Jones, K. H., Morgan, D. B., Smith, J. W. G. Br. J. Surg. 1963, 50, 608. 3. Jones, K. H., Fourman, P. Lancet, 1963, ii, 119. 4. Smith, J. W. G., Davis, R. H., Fourman, P. ibid. 1960, ii, 510. 5. Rose, N. ibid. ii, 116. 6. Blanchard, B. M. Archs intern. Med. 1962, 110, 382. 7. Firth, S. J. Proc. R. Soc. Med. 1962, 55, 802. 8. Petch, C. P. Lancet, 1963, ii, 124.
a
by Fox1 on the relaand the chronic rheumatic
paper
diphtheroid organisms
JAMES G. SOMMERVILLE.
&agr;-NAPHTHYLAMINE TEST FOR BACTERIURIA SIR,-One of the reagents used in the Griess-Ilosvay nitrite test, oc-naphthylamine, has recently been cited as a potential cause of tumours of the urinary tract. In the past this test, in addition to its other applications, has been recommended for the detection of significant bacteriuria.3 4 In the U.S.A. it is available as a commercially prepared kit and possibly its use could become widespread in this country. We feel that potential users of oc-naphthylamine should be made aware of the risks involved and the strict precautions that have been recommended in handling the compound.2 A substitute for oc-naphthylamine has been suggested for other applications of the test,5 and this may prove satisfactory when used to detect bacteriuria. Chase Farm Hospital, N. A. SIMMONS. Enfield, Middlesex. Road Dudley Hospital, J. D. WILLIAMS. Birmingham 18.
BACTERIA IN ACUTE OTITIS MEDIA SIR,-Dr. May’s letter (Feb. 18, p. 390) raises some interesting points which I shall try to answer. I assume that he would be prepared to accept that the potential pathogenicity of P-haemolytic streptococci, pneumococci, Staphylococcus pyogenes and, at any rate, some serotypes of Haemophilus influenzae, has been amply demonstrated in several situations. The question at issue is whether or not these organisms are capable of causing or contributing to acute inflammation of the middle ear. The available evidence suggests that they can and do. It has been shown that the injection of pneumococci into the middle ear of the guineapig results in otitis (Pseudomonas pyocyanea [aeruginosa] is even more effective in this respect), but attempts with Streptococcus pyogenes have proved less rewarding.In the absence of similar attempts to reproduce the disease in human volunteers one has to rely on clinical findings. I submit that the repeated isolation of one, or rarely more than two, species of these organisms, in a heavy growth on direct plating, from a site showing undoubted evidence of acute inflammation, makes it probable that they are acting in a pathogenic role. Dr. May suggests that they may be nonpathogenic contaminants from the nasopharynx, but, if this is so, it seems strange that other less obviously pathogenic members of the nasopharyngeal flora, such as Neisseria spp., Strep. viridans, and diphtheroids, are rarely isolated at the same time. I do not wish to suggest that bacteria are the sole cause of this infection, for the association of acute otitis with viral infections of the upper respiratory tract is well known. This infection may indeed be due to a direct action of the virus on the middle ear, but attempts made to isolate virus from the ear have proved negative.7 It is also possible that Mycoplasma spp. and hartmanella amoebae may play a part in pathogenesis. 1. Fox, W. W. Rheumatism, 1950, 6, 33. 2. Gaz. Inst. med. Lab. Technol. 1966, 10, 147. 3. Turner, G. C. Lancet, 1961, ii, 1062. 4. Sleigh, J. D., Robertson, J. G., Isdale, M. H. J. Obstet Gynœc. Br. Commonw. 1964, 71, 74. 5. McLean, J., Henderson, A. J. clin. Path. 1966, 19, 632. 6. Friedmann, I. J. Lar. Otol. 1955, 69, 27. 7. Grönroos, J. A., Kortekangas, A. E., Ojala, L., Vuori, M. Acta oto.-lar. 1964, 58, 149.
answer is simple-even if its implicadisturbing. Perhaps rheumatoid arthritis is not a complaint-a disorder. Perhaps it is a way by which a patient intimates, in pathological terms, that he is complaining. He may, of course, be disposed by heredity to rheumatism rather than to other complaints; or he may have some constitutional
Why ?
tions
are
occupational bias towards it. But the actual emergence of the symptoms may represent the psyche’s cry for help. Suggestion, it has now often been shown, is capable of answering that cry as effectively as drugs. But how much attention is currently being given to research into how to employ it more
or
effectively ? BRIAN INGLIS.
London W.2.
OSMOMETRY SIR,-Dr. Dormandy, in his interesting Occasional Survey (Feb. 4, p. 267), points out the theoretical objections to the measurement of osmolality by cryoscopic methods. He also stresses the advantages of thinking in terms of vapour pressure when considering osmolality. We have not had any experience with cryoscopic methods but agree with Dr. Dormandy that, whatever the theoretical objections, they are satisfactory for most clinical purposes if they give a satisfactory degree of accuracy for the particular problem being studied. In recent experiments we have been able to measure osmolality using a’Mechrolab ’ 301A osmometer which Professor H. S. Heller (department of pharmacology, Bristol University) has CHANGES IN PLASMA-OSMOLALITY, URINE-OSMOLALITY, AND URINEFLOW RATES IN TWO NORMAL SUBJECTS GIVEN A WATER-LOAD AT 8.30 A.M.
Plasma-samples taken
at start
of each period.
generously made available. This instrument does, in fact, directly the vapour pressure of the solution. We still express our results in mosmoles per kg., based on a calibration curve obtained using standard sodium-chloride solutions. With this instrument it is possible to obtain consistent results in the range of 250-320 mosmoles per kg. with 95% confidence limits of less than 4 mosmoles per kg. After the initial calibration each estimation takes 21/2 minutes. Using this instrument, we have obtained results which conflict with some of the conclusions reached by Dr. Dormandy and his colleagues in their preliminary communication (Feb. 4, p. 246) on the constancy of plasma-osmolality. Our results are very similar to those obtained by Baldes and Smirk, White and Findley,2 and other workers quoted by Homer Smith3 in studies of plasma during water-loading experiments. In the accompanying table are the changes observed in two normal subjects after oral ingestion of a water-load (18 ml. per kg. body-weight) at 8.30 A.M. This water-load, which is similar to that used by Dr. Dormandy and his colleagues in their volunteers, can be seen to produce a fall in plasma-osmolality which precedes the onset of the diuresis. Following the excre-
measure
1. Baldes, E. J., Smirk, F. H. J. Physiol., Lond. 1934, 82, 62. 2. White, H. L., Findley, T. Am. J. Physiol. 1937, 119, 740. 3. Homer Smith, W. The Kidney. London, 1951.
tion of a large amount of hypotonic urine, the plasma-osmolality can be seen to be returning towards basal levels. These findings correspond to those of the other authors cited and provide evidence for the small shifts in plasma-osmolality which precede water diuresis and which Dr. Dormandy suggests must occur but which he did not detect in his experiments. The alteration in plasma-osmolality which was observed is greater than the 1 % change which Verney4 demonstrated was necessary to produce antidiuresis in dogs when he perfused their carotid arteries with slightly hypertonic saline solutions. It seems most likely that the fall in osmolality which we have observed inhibits the secretion of antidiuretic hormone and the delay between this fall and the onset and peak of diuresis is attributable to the duration of action of antidiuretic hormone. This does not, of course, exclude the possibility that active renal excretion of water may occur either because of the reduced secretion of antidiuretic hormone or from some direct effect of the drop in plasma-osmolality on the kidney. We will await the results of further experiments and also the publication in more detail of those presented in the preliminary communication of Dr. Dormandy and his colleagues before accepting that active excretion of water by the kidney tubule does occur. MARTIN S. KNAPP PAUL M. KEANE. Bristol Royal Infirmary.
THE CONTROL OF VENEREAL DISEASE SIR,-A far greater problem in the control of the spread of venereal disease than the female contact who, having been traced, refuses to cooperate are those who cannot be traced at all. In this clinic, during a period of twelve months, 39-85% of the female contacts of the men attending with gonorrhoea were traced and attended either here or elsewhere, 60.15% could not be traced, and only 0-73% were traced and refused to attend. Failure to trace the contact was almost always due to genuine lack of information of sufficient personal details. Contact tracing is essential and valuable but can do nothing to reach this large group of unidentifiable women, and this aspect of the problem needs continuing study and a different line of approach. There are several reasons why women do not attend a clinic of their own accord. The most obvious one is the absence of symptoms in uncomplicated gonorrhoea in the female. Equally important factors are that women appear to have a less realistic attitude than men to the risks of casual encounters, and are more frightened at the idea of attending a clinic. Unfortunately many members of the medical profession are also slow to appreciate the need for special investigations in women who have been at risk, and at times seem to reflect their patients’ dislike and distrust of the " special clinic ". Women should be referred for examination and should be encouraged to request examination whenever they have been at risk. Doctors should also encourage their patients to regard the special clinics, not as places to be visited only in the last resort, but as ordinary outpatient departments offering a useful service in the diagnosis of all types of genital infections as well as in the treatment of venereal disease. In this connection, much more use could be made of routine screening procedures-e.g., on patients attending antenatal clinics. To reintroduce compulsory powers over " persons suspected of having venereal disease " would have a very damaging effect on progress along these lines, and would undo much of the good work which has been done in recent years in improving the standard of clinics and the relationship between venereologists and their colleagues in other branches of medicine. My personal objections to the idea of forcibly examining patients are so strong that I would not be associated with any such procedures, but I shall not enlarge on the moral aspects which have been admirably dealt with by previous correspondents. The point I wish to emphasise is that, in my view, the number of patients who would be frightened away 4. Verney, E. B. Proc. R. Soc. 1947,
135,
25.
442 from the clinics if powers of compulsion were employed would far exceed the numbers of those forced to accept examination and treatment by these means. Department of Venereology, King’s College Hospital, EVA GALLAGHER. London S.E.5.
DIPHTHEROIDS AND RHEUMATOID ARTHRITIS SiR,ŃThe preliminary communication by Dr. Duthie and his co-workers (Jan. 21, p. 142) certainly justifies further
investigation. tion between diseases.
This work recalls
Medical Rehabilitation Centre, 152 Camden Road, London N.W.1.
TESTING FOR HYPOPARATHYROIDISM SIR,-In 1963Iexpressed doubt whether partial hypoparathyroidism (defined as impaired response to a calciumdeprivation test in patients with normal serum-calcium levels) could cause symptoms, and hoped that Dr. (now Prof.) P. Fourman’s group would carry out a double-blind trial on their patients with this condition. This they had already embarked on,2 but no results have yet appeared. Dr. Stowers and his colleagues (Jan. 21, p. 124) have now tried to fill this gap in our knowledge with a double-blind crossover trial of calcium gluconate in patients with partial hypoparathyroidism identified by trisodium-edetate (T.S.E.) infusion,3 from whi@h they conclude that these patients’ symptoms were unrelated to their defect in parathyroid function. It should be gratifying to find my prediction confirmed, but unfortunately their work is open to the serious objection that the dose of calcium gluconate used was far too small. Fourman et a1.2 reported on the results of treatment (uncontrolled) in a series of 46 patients with different degrees of parathyroid insufficiency. 12 of these patients, identified by either sodium-phytate loading4 or T.s.E. infusion,3 had an initial serum-calcium level of 8-50 mg. per 100 ml. or greater, and were treated with calcium alone in doses of 3-4 g. daily. It was claimed that 5 of these patients, whose mean serum-calcium levels increased by 0-52 mg. per 100 ml. (from 8-98 to 9-50 mg. per 100 ml.) had partial relief of symptoms, and that the remaining 7, whose mean serum-calcium levels increased by 0-76 mg. per 100 ml. (from 9.12 to 9-88 mg. per 100 ml.), had complete relief of symptoms. Clearly, to rebut the claim that a rise in serum-calcium level of this order can lead to symptomatic improvement, it is necessary to give sufficient calcium to the subjects of a double-blind trial to produce such a rise, or to prove that such a rise cannot be achieved by 3-4 g. of calcium daily. Since Dr. Stowers and his colleagues gave their patients only 0-72 g. of calcium daily, and did not achieve any rise in serum-calcium levels, no symptomatic improvement was to be expected, regardless of the nature of their patients’ symptoms. Rosegave her patients 3 g. of calcium daily, but unfortunately none of them had partial hypoparathyroidism as defined above, although the fact that they had the same symptoms tends to discredit the relationship of such symptoms to impaired parathyroid function. I remain sceptical of the claim that so small a rise in serumcalcium level can be of so great therapeutic benefit, but it is still unrefuted seven years after the concept of partial hypoparathyroidism was revived.4 Even if the results of their trial were accepted, the conclusion by Dr. Stowers and his colleagues that partial hypoparathyroidism has no clinical reality would be unjustified. An impaired response to calcium deprivation, even if it does not cause symptoms or require treatment, probably indicates decreased parathyroid function, and such patients should surely be kept under observation in case they develop convulsions many years later.6-8 Medical Professorial Unit, University of Queensland, Brisbane Hospital, A. M. PARFITT. Brisbane, Australia. 1. Parfitt, A. M. Lancet, 1963, ii, 465. 2. Fourman, P., Davis, R. H., Jones, K. H., Morgan, D. B., Smith, J. W. G. Br. J. Surg. 1963, 50, 608. 3. Jones, K. H., Fourman, P. Lancet, 1963, ii, 119. 4. Smith, J. W. G., Davis, R. H., Fourman, P. ibid. 1960, ii, 510. 5. Rose, N. ibid. ii, 116. 6. Blanchard, B. M. Archs intern. Med. 1962, 110, 382. 7. Firth, S. J. Proc. R. Soc. Med. 1962, 55, 802. 8. Petch, C. P. Lancet, 1963, ii, 124.
a
by Fox1 on the relaand the chronic rheumatic
paper
diphtheroid organisms
JAMES G. SOMMERVILLE.
&agr;-NAPHTHYLAMINE TEST FOR BACTERIURIA SIR,-One of the reagents used in the Griess-Ilosvay nitrite test, oc-naphthylamine, has recently been cited as a potential cause of tumours of the urinary tract. In the past this test, in addition to its other applications, has been recommended for the detection of significant bacteriuria.3 4 In the U.S.A. it is available as a commercially prepared kit and possibly its use could become widespread in this country. We feel that potential users of oc-naphthylamine should be made aware of the risks involved and the strict precautions that have been recommended in handling the compound.2 A substitute for oc-naphthylamine has been suggested for other applications of the test,5 and this may prove satisfactory when used to detect bacteriuria. Chase Farm Hospital, N. A. SIMMONS. Enfield, Middlesex. Road Dudley Hospital, J. D. WILLIAMS. Birmingham 18.
BACTERIA IN ACUTE OTITIS MEDIA SIR,-Dr. May’s letter (Feb. 18, p. 390) raises some interesting points which I shall try to answer. I assume that he would be prepared to accept that the potential pathogenicity of P-haemolytic streptococci, pneumococci, Staphylococcus pyogenes and, at any rate, some serotypes of Haemophilus influenzae, has been amply demonstrated in several situations. The question at issue is whether or not these organisms are capable of causing or contributing to acute inflammation of the middle ear. The available evidence suggests that they can and do. It has been shown that the injection of pneumococci into the middle ear of the guineapig results in otitis (Pseudomonas pyocyanea [aeruginosa] is even more effective in this respect), but attempts with Streptococcus pyogenes have proved less rewarding.In the absence of similar attempts to reproduce the disease in human volunteers one has to rely on clinical findings. I submit that the repeated isolation of one, or rarely more than two, species of these organisms, in a heavy growth on direct plating, from a site showing undoubted evidence of acute inflammation, makes it probable that they are acting in a pathogenic role. Dr. May suggests that they may be nonpathogenic contaminants from the nasopharynx, but, if this is so, it seems strange that other less obviously pathogenic members of the nasopharyngeal flora, such as Neisseria spp., Strep. viridans, and diphtheroids, are rarely isolated at the same time. I do not wish to suggest that bacteria are the sole cause of this infection, for the association of acute otitis with viral infections of the upper respiratory tract is well known. This infection may indeed be due to a direct action of the virus on the middle ear, but attempts made to isolate virus from the ear have proved negative.7 It is also possible that Mycoplasma spp. and hartmanella amoebae may play a part in pathogenesis. 1. Fox, W. W. Rheumatism, 1950, 6, 33. 2. Gaz. Inst. med. Lab. Technol. 1966, 10, 147. 3. Turner, G. C. Lancet, 1961, ii, 1062. 4. Sleigh, J. D., Robertson, J. G., Isdale, M. H. J. Obstet Gynœc. Br. Commonw. 1964, 71, 74. 5. McLean, J., Henderson, A. J. clin. Path. 1966, 19, 632. 6. Friedmann, I. J. Lar. Otol. 1955, 69, 27. 7. Grönroos, J. A., Kortekangas, A. E., Ojala, L., Vuori, M. Acta oto.-lar. 1964, 58, 149.