651 cardIOvascular signs of essential hypertension. The arterial pressure is raised by myocardial stimulation (calcium facili-
tation), the alpha-adrenoceptor blood-vessels of the fingers
are
dilated and the beta-adrenoceptor blood-vessels of the skeletal muscles are constricted as the result of sympathetic blockade
hypertension of at, presumably, ganglionic ketamine is unaffected by beta-adrenoceptor blockade but is reversed by verapamil, halothane, or d-tubocurarine. Neither halothane nor d-tubocurarine would be used to treat essential hypertension, except during surgery. The similarity between the cardiac effects of the two drugs and those of verapamil suggests that verapamil may be worth a clinical trial as an antihypertensive agent, especially in patients whose essential hypertension is resistant to sympatholytic therapy.
I thank Dr
Mary Mackenzie for providing
cervical swabs from
family-planmng patients. Department of Laboratory Medicine, Ruchill Hospital, Glasgow G20 9NB
R. J. FALLON
level. The arterial
Department of Anæsthetics, Royal Infirmary, Manchester M13 9WL
MICHAEL
JOHNSTONE
ANTISTREPTOLYSIN ACTIVITY IN STAPHYLOCOCCAL INFECTION
SiR,-In detection of significant levels of antistreptolysin
antibody (A.S.O) by the latex test, serum is first absorbed with streptolysin at a concentration sufficient to remove antibody at titres below 200. Residual antibody then agglutinates latex particles coated with streptolysin. Sera which may give falsepositive A.s.0 results in the standard haemolysin-inhibition test (e.g., in cholestatic liver disease and in nephrosis2) are usually in the latex test. The latex test is claimed by the manufacturers (Hoechst A. G.) to be unaffected by cholesterol. However, the case reported here indicates that caution is required in interpretation of antistreptolysin results. A 6-year-old boy was admitted with a 2-day history of pain in the region of the left knee and generally feeling unwell. There was no history of trauma, but 10 days previously he had had tonsillectomy because of repeated sore throats. On examination he was febrile (38-5C) and there was pain and limitation of movement of both left knee and hip. Some hours after admission he had pains in both shoulders, elbows, and wrists although movement was not limited in these joints. He was then noted to have a macular erythematous rash on the trunk, thorax, and lower part of the face. His pharynx was red and congested with pustular areas in the tonsillar bed, and cervical lymph-nodes were enlarged and tender on both sides. He had a leucocytosis of 33 000/1, 80% of which were polymorphonuclear cells. Blood taken on admission was cultured but no organisms grew. An initial specimen of serum and one collected some 5 days later gave the following results:
negative
GROUP-B STREPTOCOCCI IN THE NEWBORN
SIR,-Your interesting editorial (March 5, p. 520) prompts
why have relatively few reports appeared in British journals relating to the significance of group-B streptococci as neonatal pathogens compared with the increasing number of observations published in the American and Scandinavian literature? Although any new finding tends to stimulate others to record their observations and to recognise problems of which they were not previously aware, it is difficult to believe that, with the good laboratory services generally available in the U.K., an increased prevalence of infection would not have been noted and commented on. Is there a real difference in the prevalence of group-B streptococcal disease in North America and Britain? There is an explanation for the American finding, referred to in the editorial, of a group-B streptococcal carriage-rate of 23% in women in the third trimester of pregnancy. The American workers used a selective fluid medium which would tend to produce a much higher isolation-rate than would standard culture techniques, and in their own hands this was so, the isolation-rate rising from 14% to 34% when the new technique was used. In 1350 vaginal swabs sent by general practitioners, whether from pregnant or non-pregnant women, we found a carriage-rate of 7.5% by standard culture techniques without enrichment. 100 of these specimens were cervical swabs from family-planning patients with no disease (although 34 had some discharge on examination). The carriage-rate in these cases was only 2%; perhaps vaginal swabs are more likely than cervical swabs to detect group-B streptococci. Group-B streptococci are not uncommon in a wide range of infections. Last year, of 326 haemolytic streptococci of groups A, B, C, G, and F isolated from medical or general practice patients, 27% were of group B. Most of these came from vaginal swabs or from urine (where they may often have been contaminants or occasionally pathogens). However, of a total of 89 strains, 15 came from the oropharynx, 5 from skin or wound sepsis, and 8 from sputum. We continue to find the production of pigment on Columbia agar incubated in an atmosphere of hydrogen and carbon dioxideauseful aid to the rapid recognition of group-B streptococci from clinical sites and have yet to find a situation where pigment-producing organisms identified as a streptococcus were not of group B. This emphasises the validity of the observation and also that a saving in serum and technician time can be achieved because the need for formal Lancefield grouping is avoided. the question,
1 Baker, C. J., and others. J. Pediat. 1973, 83, 919. 2. Kexel, G. Z. Hyg. InfektKrankh. 1965, 151, 336. 3 Mhalu, F. S. J. clin. Path. 1976, 29, 309. 4 Fallon, R. J. ibid. 1974, 27, 902.
Test
Specimen1
Specimen
30
1800
2
Antistreptolysin (titre) (hxmolysis inhibition) antistreptolysin Antistaphylolysin (titre) Latex
-
1
i.u
+
6 units
The antistaphylolysin test titre subsequently rose to 8 units. 1 ml volumes of the sera were mixed with 0.02 ml of 10% dextran sulphate and 0.1 1 ml of 1 mol/1 calcium chloride in order to precipitate the beta-lipoprotein fraction. After centrifugation the supernatant was removed and the deposit redissolved in 0-85% saline, the excess calcium chloride being removed by dialysis. Standard antistreptolysin haemolysis-inhibition tests on the supernatant fluid gave a titre of 20 i.u. in the second specimen whereas the beta-lipoprotein fraction gave a titre of 1800, similar to that of the original sample, indicating that all the activity was located in the lipoprotein moiety. About 3 days after the boy’s admission the left leg became swollen and indurated below the knee but the cellulitis rapidly resolved with a course of fusidic acid and erythromycin. This patient had a staphylococcal infection and the serum A. s.0 activity was entirely due to altered beta-lipoprotein. We have previously shown raised levels of antistreptolysin factor activity (A.S.F.) of this type in 24% of 357patients with proven disease and with raised antistaphylolysin levels.3 We have also found that A.s.F. activity is associated with peptide fragments of beta-lipoproteins with molecular weights between 25 000 and 100 000 in which cholesterol molecules are suitably exposed and available for binding to streptolysin.4 Since binding of cholesterol to streptolysin is
staphylococcal
Badin, J., Cabau, M., Levy, C., Cachim, M. Ann. Biol. clin. 1962, 20, 525. Stollerman, G. H. J. clin. Invest. 1954, 33, 1233. Watson, K. C., Kerr, E. J. C. Lancet, 1975, i, 308. 4. Watson, K. C., Kerr, E. J. C. J. med. Microbiol. 1974, 8, 465.
1. 2. 3.
652 almost instantaneous it appears that competition for streptolysin in the preliminary absorption of this patient’s serum resulted in failure of the slower binding antibody molecules to attach. The residuum of unbound antibody was then sufficient to react with streptolysin bound latex. Two points should be stressed. Firstly, a positive latex test does not necessarily indicate raised antibody level. This will not usually cause confusion since the low antibody level will give only a weak latex reaction despite a high haemolysin-inhibition titre. Secondly, sera with raised antistreptolysin activity in the haemolysin-inhibition test should be further investigated to distinguish between antibody and lipoprotein activity. Apart from liver disease, nephrosis, and staphylococcal infection we have found evidence of lipoprotein activity in some patients with rheumatoid arthritis, viral infections, and tumours.
may, inadvertently, introduce a critical variable which affects differently the populations to be investigated. Thus, diet might account for the discrepant findings of Gold et al. compared with those of others, and unipolar and bipolar patients might respond differently to a low monoamine diet. Indeed, ordinary diets might also be handled differently by patients with different psychiatric illnesses when compared with each other and
K. C. WATSON E. J. C. KERR J. DRUMMOND
GROWTH HORMONE AND PROLACTIN RESPONSE TO LEVODOPA IN AFFECTIVE ILLNESS
Central Microbiological Laboratories, Western General Hospital,
Edinburgh EH4 2XU
with controls. If this is true then many comparative studies m
biological psychiatry would have to be re-evaluated. Department of Psychiatry, College of Physicians & Surgeons of Columbia University, New
GERHARD LANGER EDWARD J. SACHAR
York, N. Y. 10032, U.S.A.
et a1. reported greater prolactin suppression growth-hormone (G.H.) response to levodopa in bipolar depressed patients than in unipolar patients and controls. We have studied G.H. and prolactin response to levodopa in 43 women with affective disorders diagnosed as bipolar (18) and or unipolar (25) depression on criteria similar to those used by Gold et al. All patients were on a controlled monoamine diet and had been off drugs for at least a week before the levodopa test. After an overnight fast, patients were given 500 mg of levodopa by mouth and blood was drawn every 30 min for 120 m through a plastic indwelling catheter for radioimmunoassay of G.H. and prolactin. Unipolar patients, as a group, had a peak G.H. increment no greater than that in bipolar patients (see figure). However, when menopausal status
SIR,-Gold
and
QUALITY-CONTROL SCHEMES IN PATHOLOGY SIR,-We wish to know whether other consultant pathologists and, possibly, clinical consultants share our misgivings at the proposed change in the monitoring system of the National Quality Control Scheme for Clinical Chemistry. We feel that a central authority is appropriating a right to interfere with a consultant’s management of his department. We deplore the change, the manner of its presentation to the profession, and the long-term implications, and we are concerned lest such proposed changes may be considered as precedents, so that similar alterations in quality-control schemes in other disciplines of pathology would be proposed in due course. Department of Pathology, Hospital, Wolverhampton WV10 0QP New Cross
A. G. JACOBS I. A. HARPER W. S. A. ALLAN
was
taken into account,
a
difference in
G.H.
response
dopa emerged between bipolar premenopausal 1. 2.
to
levo-
women com-
Gold, P. W., and others, Lancet, 1976, ii, 1308. Endicott, J., Spitzer, R. L. Archs. gen. Psychiat. 1972, 29, 678.
DIET AND GROWTH-HORMONE RESPONSE IN AFFECTIVE ILLNESS
SIR,-Gold
al.’ showed that
bipolar depressive patients significant larger peak growth-hormone (G.H.) response to oral levodopa than healthy controls and unipolar depressive patients. Their findings contrast with those of Sachar et al.2 who found no difference in G.H. response to levodopa between unipolar and bipolar depressed male patients, and with those of Mendels et al. who used another test of dopaminergic influences on G.H. secretion (by apomorphine stimulation) and found no differences among depressed and manic male pahad
et
a
tients. Furthermore, stimulation tests of G.H. secretion by insulin hypoglycxmia4 and dextroamphetamine,5 which probably involve noradrenergic mechanisms, have demonstrated striking differences between unipolar depressives and controls. Gold et al. emphasise that all their subjects were on a controlled monoamine diet, whereas the four studies we have cited were not controlled for monoamine diet. Interestingly, three of Gold’s colleagues have found normals and depressives to respond differently to a monoaminergic diet and its discontinuation as evidenced by urinary 3-methoxy-4-hydroxyphenylglycol excretion, a postulated indicator of brain noradrenaline metabolism.6 This suggests that the low monoaminergic diet Gold, P. W., Goodwin, F. K., Wehr, T., Rebar, R., Sack, R. Lancet, 1976, ii, 1308. 2. Sachar, E. J., and others. Archs gen. Psychiat 1975, 32, 502. 3. Mendels, J., and others. Unpublished. 4. Gruen, P. H., Sachar, E. J., and others. Archs gen. Psychiat. 1975, 32, 31. 5. Langer, G., and others. ibid. 1976, 33, 1971. 6. Muscettola, G., Wehr, T., Goodwin, F. K., Presented at the American Psychiatric Association meeting held in Miami, in May, 1976 (New Res. Abst p. 8). 1.
Min
G.H. and
prolactin response (mean±S.E.M.). all patients. premenopausal.
=
— — —
-
-----=
postmenopausal.
to
Min
levodopa
in
depressed patients
tation), the alpha-adrenoceptor blood-vessels of the fingers
are
dilated and the beta-adrenoceptor blood-vessels of the skeletal muscles are constricted as the result of sympathetic blockade
hypertension of at, presumably, ganglionic ketamine is unaffected by beta-adrenoceptor blockade but is reversed by verapamil, halothane, or d-tubocurarine. Neither halothane nor d-tubocurarine would be used to treat essential hypertension, except during surgery. The similarity between the cardiac effects of the two drugs and those of verapamil suggests that verapamil may be worth a clinical trial as an antihypertensive agent, especially in patients whose essential hypertension is resistant to sympatholytic therapy.
I thank Dr
Mary Mackenzie for providing
cervical swabs from
family-planmng patients. Department of Laboratory Medicine, Ruchill Hospital, Glasgow G20 9NB
R. J. FALLON
level. The arterial
Department of Anæsthetics, Royal Infirmary, Manchester M13 9WL
MICHAEL
JOHNSTONE
ANTISTREPTOLYSIN ACTIVITY IN STAPHYLOCOCCAL INFECTION
SiR,-In detection of significant levels of antistreptolysin
antibody (A.S.O) by the latex test, serum is first absorbed with streptolysin at a concentration sufficient to remove antibody at titres below 200. Residual antibody then agglutinates latex particles coated with streptolysin. Sera which may give falsepositive A.s.0 results in the standard haemolysin-inhibition test (e.g., in cholestatic liver disease and in nephrosis2) are usually in the latex test. The latex test is claimed by the manufacturers (Hoechst A. G.) to be unaffected by cholesterol. However, the case reported here indicates that caution is required in interpretation of antistreptolysin results. A 6-year-old boy was admitted with a 2-day history of pain in the region of the left knee and generally feeling unwell. There was no history of trauma, but 10 days previously he had had tonsillectomy because of repeated sore throats. On examination he was febrile (38-5C) and there was pain and limitation of movement of both left knee and hip. Some hours after admission he had pains in both shoulders, elbows, and wrists although movement was not limited in these joints. He was then noted to have a macular erythematous rash on the trunk, thorax, and lower part of the face. His pharynx was red and congested with pustular areas in the tonsillar bed, and cervical lymph-nodes were enlarged and tender on both sides. He had a leucocytosis of 33 000/1, 80% of which were polymorphonuclear cells. Blood taken on admission was cultured but no organisms grew. An initial specimen of serum and one collected some 5 days later gave the following results:
negative
GROUP-B STREPTOCOCCI IN THE NEWBORN
SIR,-Your interesting editorial (March 5, p. 520) prompts
why have relatively few reports appeared in British journals relating to the significance of group-B streptococci as neonatal pathogens compared with the increasing number of observations published in the American and Scandinavian literature? Although any new finding tends to stimulate others to record their observations and to recognise problems of which they were not previously aware, it is difficult to believe that, with the good laboratory services generally available in the U.K., an increased prevalence of infection would not have been noted and commented on. Is there a real difference in the prevalence of group-B streptococcal disease in North America and Britain? There is an explanation for the American finding, referred to in the editorial, of a group-B streptococcal carriage-rate of 23% in women in the third trimester of pregnancy. The American workers used a selective fluid medium which would tend to produce a much higher isolation-rate than would standard culture techniques, and in their own hands this was so, the isolation-rate rising from 14% to 34% when the new technique was used. In 1350 vaginal swabs sent by general practitioners, whether from pregnant or non-pregnant women, we found a carriage-rate of 7.5% by standard culture techniques without enrichment. 100 of these specimens were cervical swabs from family-planning patients with no disease (although 34 had some discharge on examination). The carriage-rate in these cases was only 2%; perhaps vaginal swabs are more likely than cervical swabs to detect group-B streptococci. Group-B streptococci are not uncommon in a wide range of infections. Last year, of 326 haemolytic streptococci of groups A, B, C, G, and F isolated from medical or general practice patients, 27% were of group B. Most of these came from vaginal swabs or from urine (where they may often have been contaminants or occasionally pathogens). However, of a total of 89 strains, 15 came from the oropharynx, 5 from skin or wound sepsis, and 8 from sputum. We continue to find the production of pigment on Columbia agar incubated in an atmosphere of hydrogen and carbon dioxideauseful aid to the rapid recognition of group-B streptococci from clinical sites and have yet to find a situation where pigment-producing organisms identified as a streptococcus were not of group B. This emphasises the validity of the observation and also that a saving in serum and technician time can be achieved because the need for formal Lancefield grouping is avoided. the question,
1 Baker, C. J., and others. J. Pediat. 1973, 83, 919. 2. Kexel, G. Z. Hyg. InfektKrankh. 1965, 151, 336. 3 Mhalu, F. S. J. clin. Path. 1976, 29, 309. 4 Fallon, R. J. ibid. 1974, 27, 902.
Test
Specimen1
Specimen
30
1800
2
Antistreptolysin (titre) (hxmolysis inhibition) antistreptolysin Antistaphylolysin (titre) Latex
-
1
i.u
+
6 units
The antistaphylolysin test titre subsequently rose to 8 units. 1 ml volumes of the sera were mixed with 0.02 ml of 10% dextran sulphate and 0.1 1 ml of 1 mol/1 calcium chloride in order to precipitate the beta-lipoprotein fraction. After centrifugation the supernatant was removed and the deposit redissolved in 0-85% saline, the excess calcium chloride being removed by dialysis. Standard antistreptolysin haemolysis-inhibition tests on the supernatant fluid gave a titre of 20 i.u. in the second specimen whereas the beta-lipoprotein fraction gave a titre of 1800, similar to that of the original sample, indicating that all the activity was located in the lipoprotein moiety. About 3 days after the boy’s admission the left leg became swollen and indurated below the knee but the cellulitis rapidly resolved with a course of fusidic acid and erythromycin. This patient had a staphylococcal infection and the serum A. s.0 activity was entirely due to altered beta-lipoprotein. We have previously shown raised levels of antistreptolysin factor activity (A.S.F.) of this type in 24% of 357patients with proven disease and with raised antistaphylolysin levels.3 We have also found that A.s.F. activity is associated with peptide fragments of beta-lipoproteins with molecular weights between 25 000 and 100 000 in which cholesterol molecules are suitably exposed and available for binding to streptolysin.4 Since binding of cholesterol to streptolysin is
staphylococcal
Badin, J., Cabau, M., Levy, C., Cachim, M. Ann. Biol. clin. 1962, 20, 525. Stollerman, G. H. J. clin. Invest. 1954, 33, 1233. Watson, K. C., Kerr, E. J. C. Lancet, 1975, i, 308. 4. Watson, K. C., Kerr, E. J. C. J. med. Microbiol. 1974, 8, 465.
1. 2. 3.
652 almost instantaneous it appears that competition for streptolysin in the preliminary absorption of this patient’s serum resulted in failure of the slower binding antibody molecules to attach. The residuum of unbound antibody was then sufficient to react with streptolysin bound latex. Two points should be stressed. Firstly, a positive latex test does not necessarily indicate raised antibody level. This will not usually cause confusion since the low antibody level will give only a weak latex reaction despite a high haemolysin-inhibition titre. Secondly, sera with raised antistreptolysin activity in the haemolysin-inhibition test should be further investigated to distinguish between antibody and lipoprotein activity. Apart from liver disease, nephrosis, and staphylococcal infection we have found evidence of lipoprotein activity in some patients with rheumatoid arthritis, viral infections, and tumours.
may, inadvertently, introduce a critical variable which affects differently the populations to be investigated. Thus, diet might account for the discrepant findings of Gold et al. compared with those of others, and unipolar and bipolar patients might respond differently to a low monoamine diet. Indeed, ordinary diets might also be handled differently by patients with different psychiatric illnesses when compared with each other and
K. C. WATSON E. J. C. KERR J. DRUMMOND
GROWTH HORMONE AND PROLACTIN RESPONSE TO LEVODOPA IN AFFECTIVE ILLNESS
Central Microbiological Laboratories, Western General Hospital,
Edinburgh EH4 2XU
with controls. If this is true then many comparative studies m
biological psychiatry would have to be re-evaluated. Department of Psychiatry, College of Physicians & Surgeons of Columbia University, New
GERHARD LANGER EDWARD J. SACHAR
York, N. Y. 10032, U.S.A.
et a1. reported greater prolactin suppression growth-hormone (G.H.) response to levodopa in bipolar depressed patients than in unipolar patients and controls. We have studied G.H. and prolactin response to levodopa in 43 women with affective disorders diagnosed as bipolar (18) and or unipolar (25) depression on criteria similar to those used by Gold et al. All patients were on a controlled monoamine diet and had been off drugs for at least a week before the levodopa test. After an overnight fast, patients were given 500 mg of levodopa by mouth and blood was drawn every 30 min for 120 m through a plastic indwelling catheter for radioimmunoassay of G.H. and prolactin. Unipolar patients, as a group, had a peak G.H. increment no greater than that in bipolar patients (see figure). However, when menopausal status
SIR,-Gold
and
QUALITY-CONTROL SCHEMES IN PATHOLOGY SIR,-We wish to know whether other consultant pathologists and, possibly, clinical consultants share our misgivings at the proposed change in the monitoring system of the National Quality Control Scheme for Clinical Chemistry. We feel that a central authority is appropriating a right to interfere with a consultant’s management of his department. We deplore the change, the manner of its presentation to the profession, and the long-term implications, and we are concerned lest such proposed changes may be considered as precedents, so that similar alterations in quality-control schemes in other disciplines of pathology would be proposed in due course. Department of Pathology, Hospital, Wolverhampton WV10 0QP New Cross
A. G. JACOBS I. A. HARPER W. S. A. ALLAN
was
taken into account,
a
difference in
G.H.
response
dopa emerged between bipolar premenopausal 1. 2.
to
levo-
women com-
Gold, P. W., and others, Lancet, 1976, ii, 1308. Endicott, J., Spitzer, R. L. Archs. gen. Psychiat. 1972, 29, 678.
DIET AND GROWTH-HORMONE RESPONSE IN AFFECTIVE ILLNESS
SIR,-Gold
al.’ showed that
bipolar depressive patients significant larger peak growth-hormone (G.H.) response to oral levodopa than healthy controls and unipolar depressive patients. Their findings contrast with those of Sachar et al.2 who found no difference in G.H. response to levodopa between unipolar and bipolar depressed male patients, and with those of Mendels et al. who used another test of dopaminergic influences on G.H. secretion (by apomorphine stimulation) and found no differences among depressed and manic male pahad
et
a
tients. Furthermore, stimulation tests of G.H. secretion by insulin hypoglycxmia4 and dextroamphetamine,5 which probably involve noradrenergic mechanisms, have demonstrated striking differences between unipolar depressives and controls. Gold et al. emphasise that all their subjects were on a controlled monoamine diet, whereas the four studies we have cited were not controlled for monoamine diet. Interestingly, three of Gold’s colleagues have found normals and depressives to respond differently to a monoaminergic diet and its discontinuation as evidenced by urinary 3-methoxy-4-hydroxyphenylglycol excretion, a postulated indicator of brain noradrenaline metabolism.6 This suggests that the low monoaminergic diet Gold, P. W., Goodwin, F. K., Wehr, T., Rebar, R., Sack, R. Lancet, 1976, ii, 1308. 2. Sachar, E. J., and others. Archs gen. Psychiat 1975, 32, 502. 3. Mendels, J., and others. Unpublished. 4. Gruen, P. H., Sachar, E. J., and others. Archs gen. Psychiat. 1975, 32, 31. 5. Langer, G., and others. ibid. 1976, 33, 1971. 6. Muscettola, G., Wehr, T., Goodwin, F. K., Presented at the American Psychiatric Association meeting held in Miami, in May, 1976 (New Res. Abst p. 8). 1.
Min
G.H. and
prolactin response (mean±S.E.M.). all patients. premenopausal.
=
— — —
-
-----=
postmenopausal.
to
Min
levodopa
in
depressed patients
