47 surgery, could be relevant to the early clinical which is sometimes seen after thymectomy. Institute of Pharmacology, C.N.R. Centre for Cytopharmacology,
University of Milan, and "C. Besta" Neurological Institute,
Milan, Italy
improvement
B. CONTI TRONCONI M. MORGUTTI F. CORNELIO F. CLEMENTI
INCREASED UPTAKE OF ACETYLCHOLINE-RECEPTOR ANTIBODY AT MOTOR ENDPLATE IN MYASTHENIC EXACERBATION
SIR,-Assay for antibodies to human nicotine acetylcholine receptor (anti-AChR) in serum is a diagnostic tool in myasthenia gravis (M.G.). Titres determined once, at any time of the disease, do not seem to correlate with disease severity or to have prognostic value.’ We measured anti-AChR antibody titres two or more times in five patients in a fairly stable condition before and up to 2 years after thymectomy and found no significant change. However, two recent cases suggest that anti-AChR titres may shed some light on the physiopathological mechanisms of exacerbations of M.G. Case1 This 31-year-old woman has had M.G. since 1964. She had thymectomy in 1969 for a moderately severe, generalised condition (Osserman lib). Striking medullary hyperplasia and proliferation of germinative centres of the thymus were noted on microscopic examination. Progressive improvement permitted withdrawal of pyridostigmine bromide 2yyears later, without enhancement of a slight residual facial weakness. The patient had a relapse at the end of 1975, with mild generalised M.G. (na). In May, 1976, she had no mediastinal mass on chest X-rays, and her serum anti-AChR titre was 0.61 pmol/ml. In July, 1977, she had a febrile illness for 2-3 days and was weaker for 3 weeks. On Oct. 10 she reported another exacerbation over the previous 8-10 days, and her condition was then group nb. On Oct. 10 her antibody titre was 0.12 pmol/ml. At the end of November, her condition is unchanged and her rea
In our two patients this pattern coincided with reduced antiAChR titres. This could reflect enhanced uptake at the motor endplate. Fewer receptors would then be available and the remaining ones will then be exposed to overdosage by anticholinesterases.
Neurology Service, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, and Department of Biochemistry, University of Geneva.
G. DE CROUSAZ B. W. FULPIUS
NITRITE INDICATOR STRIP TEST FOR BACTERIURIA
SiR,—Dipslide culture is the most accurate simple method for the detection of bacteriuria. Kunin and DeGroot2 assessed the reliability of another method, the nitrite indicator strip, and showed that it detected 80-85% of infections when applied to three first morning urine samples. This method has potential for use in screening for bacteriuria. We have compared the nitrite indicator strip method (’BM Test-Nitrite,’ Boehringer, Mannheim) with the dipslide technique (’Uricult’, Orion Laboratories, Helsinki) in 234 children examined in the outpatient renal clinic. A clean voided urine specimen was obtained after careful cleaning of external genitals. Specimens were immediately inoculated using the dipslide. The nitrite indicator was read 30 s after wetting the strip. DIPSLIDE
CULTURES, NITRITE TESTS, IN
234
AND URINE OSMOLALITIES
CHILDREN
sponse to anticholinesterases is reduced.
Case 2
This 16-year-old girl has had M.G. since 1973. She had a thymectomy 6 months later for insufficient response to both anticholinesterases and 10-day courses of corticotrophin. Thymic histology was normal for her age. Her weakness subsequently fluctuated within group nb. In June, 1977, her antiAChR titre was 0-91 pmol/ml. In mid-September she suddenly deteriorated, without detectable cause. On Sept. 29 her antibody level was 0-42 pmol/ml. Response to anticholinesterases was reduced. On Oct. 3 she had a myasthenic crisis, and leftbase pneumonia was found on admission to hospital. Anticholinesterases were withdrawn and respiratory support was provided for a week. Since then her generalised weakness has not improved; she had both muscarinic and nicotinic effects when the dose of pyridostigmine bromide was increased above twothirds of the previous well-tolerated levels. Parallel decreases of patients’ weakness and antibody titres have been describedl-4 as a result of immunosuppressive drugs to reduce production of antibody or thoracic-duct drainage or plasmapheresis to remove antibodies from body fluids. Both weakness and antibody titres increased when these treatments
stopped. Spontaneous
were
evolution of M.G. may not follow this parallelism. Brittle M.G. and myasthenic crises usually coincide with a reduced benefit from increased effects of anticholinesterases .5 1. Lindstrom, J. M., Lennon, V. A., Seybold, M. E., Whittingham, S. Ann. N.Y. Acad. Sci. 1976, 274, 254. 2. Lefvert, A. K., Matell, G. Acta med. scand. 1977, 201, 181 3. Lefvert, A. K., Bergström, K., Matell, G. 11th Wld. Congr. Neurol; abstr. p. 242. Amsterdam, 1977. 4. Newsom Davis, J., Pinching, A. J., Vincent, A., Wilson, S. G. ibid. p. 278. 5. Glaser, G. Ann. N.Y. Acad. Sci. 1966, 135, 335.
The results (see table) show that only 15% of outpatients with significant bacteriuria (10 colonies/ml) had positive nitrite indicator tests in a single urine sample. Clearly this test cannot replace the dipslide culture method for the detection of urinary-tract infection when only a single random urine sample is available. This does not contradict Kunin and DeGroot2 who clearly emphasised the importance of using three first morning samples and specifically discussed the use of the test in screening programmes. In our study urine osmolality was measured as a possible indicator of the frequency of micturition. All urines were hypertonic suggesting infrequent voiding in these patients. First morning urine samples, however, are likely to contain more products of bacterial metabolism than any random
daytime sample. Doctors who use nitrite indicator strips to detect bacteriuria should be careful to follow the protocol of Kunin and DeGroot very strictly. If only a single daytime urine specimen is used no valid alternative to the dipslide technique is currently available. Service de Pédiatrie, Centre Hospitalier Universitaire Vaudois,
Lausanne, Switzerland
1. Cohen, S., Kass, E. H. New Engl. J. Med. 1967, 277, 176. 2. Kunin, C. M., DeGroot, J. E, Pediatrics, 1977, 60, 244.
J. P. GUIGNARD A. TORRADO
University of Milan, and "C. Besta" Neurological Institute,
Milan, Italy
improvement
B. CONTI TRONCONI M. MORGUTTI F. CORNELIO F. CLEMENTI
INCREASED UPTAKE OF ACETYLCHOLINE-RECEPTOR ANTIBODY AT MOTOR ENDPLATE IN MYASTHENIC EXACERBATION
SIR,-Assay for antibodies to human nicotine acetylcholine receptor (anti-AChR) in serum is a diagnostic tool in myasthenia gravis (M.G.). Titres determined once, at any time of the disease, do not seem to correlate with disease severity or to have prognostic value.’ We measured anti-AChR antibody titres two or more times in five patients in a fairly stable condition before and up to 2 years after thymectomy and found no significant change. However, two recent cases suggest that anti-AChR titres may shed some light on the physiopathological mechanisms of exacerbations of M.G. Case1 This 31-year-old woman has had M.G. since 1964. She had thymectomy in 1969 for a moderately severe, generalised condition (Osserman lib). Striking medullary hyperplasia and proliferation of germinative centres of the thymus were noted on microscopic examination. Progressive improvement permitted withdrawal of pyridostigmine bromide 2yyears later, without enhancement of a slight residual facial weakness. The patient had a relapse at the end of 1975, with mild generalised M.G. (na). In May, 1976, she had no mediastinal mass on chest X-rays, and her serum anti-AChR titre was 0.61 pmol/ml. In July, 1977, she had a febrile illness for 2-3 days and was weaker for 3 weeks. On Oct. 10 she reported another exacerbation over the previous 8-10 days, and her condition was then group nb. On Oct. 10 her antibody titre was 0.12 pmol/ml. At the end of November, her condition is unchanged and her rea
In our two patients this pattern coincided with reduced antiAChR titres. This could reflect enhanced uptake at the motor endplate. Fewer receptors would then be available and the remaining ones will then be exposed to overdosage by anticholinesterases.
Neurology Service, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, and Department of Biochemistry, University of Geneva.
G. DE CROUSAZ B. W. FULPIUS
NITRITE INDICATOR STRIP TEST FOR BACTERIURIA
SiR,—Dipslide culture is the most accurate simple method for the detection of bacteriuria. Kunin and DeGroot2 assessed the reliability of another method, the nitrite indicator strip, and showed that it detected 80-85% of infections when applied to three first morning urine samples. This method has potential for use in screening for bacteriuria. We have compared the nitrite indicator strip method (’BM Test-Nitrite,’ Boehringer, Mannheim) with the dipslide technique (’Uricult’, Orion Laboratories, Helsinki) in 234 children examined in the outpatient renal clinic. A clean voided urine specimen was obtained after careful cleaning of external genitals. Specimens were immediately inoculated using the dipslide. The nitrite indicator was read 30 s after wetting the strip. DIPSLIDE
CULTURES, NITRITE TESTS, IN
234
AND URINE OSMOLALITIES
CHILDREN
sponse to anticholinesterases is reduced.
Case 2
This 16-year-old girl has had M.G. since 1973. She had a thymectomy 6 months later for insufficient response to both anticholinesterases and 10-day courses of corticotrophin. Thymic histology was normal for her age. Her weakness subsequently fluctuated within group nb. In June, 1977, her antiAChR titre was 0-91 pmol/ml. In mid-September she suddenly deteriorated, without detectable cause. On Sept. 29 her antibody level was 0-42 pmol/ml. Response to anticholinesterases was reduced. On Oct. 3 she had a myasthenic crisis, and leftbase pneumonia was found on admission to hospital. Anticholinesterases were withdrawn and respiratory support was provided for a week. Since then her generalised weakness has not improved; she had both muscarinic and nicotinic effects when the dose of pyridostigmine bromide was increased above twothirds of the previous well-tolerated levels. Parallel decreases of patients’ weakness and antibody titres have been describedl-4 as a result of immunosuppressive drugs to reduce production of antibody or thoracic-duct drainage or plasmapheresis to remove antibodies from body fluids. Both weakness and antibody titres increased when these treatments
stopped. Spontaneous
were
evolution of M.G. may not follow this parallelism. Brittle M.G. and myasthenic crises usually coincide with a reduced benefit from increased effects of anticholinesterases .5 1. Lindstrom, J. M., Lennon, V. A., Seybold, M. E., Whittingham, S. Ann. N.Y. Acad. Sci. 1976, 274, 254. 2. Lefvert, A. K., Matell, G. Acta med. scand. 1977, 201, 181 3. Lefvert, A. K., Bergström, K., Matell, G. 11th Wld. Congr. Neurol; abstr. p. 242. Amsterdam, 1977. 4. Newsom Davis, J., Pinching, A. J., Vincent, A., Wilson, S. G. ibid. p. 278. 5. Glaser, G. Ann. N.Y. Acad. Sci. 1966, 135, 335.
The results (see table) show that only 15% of outpatients with significant bacteriuria (10 colonies/ml) had positive nitrite indicator tests in a single urine sample. Clearly this test cannot replace the dipslide culture method for the detection of urinary-tract infection when only a single random urine sample is available. This does not contradict Kunin and DeGroot2 who clearly emphasised the importance of using three first morning samples and specifically discussed the use of the test in screening programmes. In our study urine osmolality was measured as a possible indicator of the frequency of micturition. All urines were hypertonic suggesting infrequent voiding in these patients. First morning urine samples, however, are likely to contain more products of bacterial metabolism than any random
daytime sample. Doctors who use nitrite indicator strips to detect bacteriuria should be careful to follow the protocol of Kunin and DeGroot very strictly. If only a single daytime urine specimen is used no valid alternative to the dipslide technique is currently available. Service de Pédiatrie, Centre Hospitalier Universitaire Vaudois,
Lausanne, Switzerland
1. Cohen, S., Kass, E. H. New Engl. J. Med. 1967, 277, 176. 2. Kunin, C. M., DeGroot, J. E, Pediatrics, 1977, 60, 244.
J. P. GUIGNARD A. TORRADO
