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DOUBTFUL SIGNIFICANCE OF FASTIDIOUS BACTERIURIA IN THE URETHRAL SYNDROME
115 BINDING TO SERUM SAMPLES COLLECTED SERIALLY FROM A
DOUBTFUL SIGNIFICANCE OF FASTIDIOUS BACTERIURIA IN THE URETHRAL SYNDROME
PREPUBERTAL GIRL AFTER STOPPING THERAPY WITH DI-SIPIDIN
et
(POSTERIOR
a1.l
have implicated "fastidious" bacteria Lactobacillus and spp.) in the "urethral (Corynebacterium svndrome" (dysuria and frequency without "significant" bacteriuria). We have cultured fresh urine from three groups of women who were not on antibiotics. Midstream urines (MSUs) were collected for screening purposes from 100 symptom-free pregnant women. The uncentrifuged urine was cultured by the filterpaper foot impression method, able to detect 104 bacteria/ml, at 37°C for one day on MacConkey agar and for five days in 5% CO2 on chocolate agar. 14 samples grew "fastidious" bacteria-8 in pure culture, 5 mixed with Staphylo,coccus epidermidis, and 1 mixed with coliforms. Urine from 94 women without urinary symptoms, with an average age of 67, was collected aseptically at the time of preoperative catheterisation and similarly cultured. 3 samples grew fastidious bacteria as a pure culture (1 at 104/ml and 2 at whilst 1 sample produced a growth of mixed fastidious bacteria at
SIR,-Maskell
105/ml),
104/ml. MSUs collected from 100 women with dysuria, frequency, and pyuria (>10 per high-power field) and which gave no growth on MacConkey agar were cultured for fastidious bacteria. These were isolated from 5 samples at >104/ml, as pure growth. We have thus found a low isolation rate of fastidious bacteria (5%) in women with the urethral syndrome that compares with the isolation rate for women without symptoms either pregnant (8% pure) or postmenopausal (4%). Drabu and Sanderson2 found a similar rate (6%) in patients with the urethral syndrome whilst Gargan et al. grew fastidious bacteria fr m women with recurrent urinary infections both with and without ymptoms. Brumfitt et a1.4 found higher isolation rates of fastidious bacteria than we did, but they too found no significant difference between the rates in healthy women and in patients with dysuria and frequency.
*All values have had
PITUITARY POWDER
SNL’FF)
negative controls subtracted.
Blood was collected serially over 2 years and sera were stored at - 20°C until analysed. Rabbit anti-hLH serum and serum from a normal adult female acted as positive and negative controls respectively. Serial dilutions, of patient and control sera up to 1 :200 000 were made in 5 mmol/1 phosphate buffer, pH 7-5. Duplicate volumes of the dilutions were dispensed into polycarbonate tubes with 1251-hLH and phosphate buffer and incubated for 5 days at 4°C. Separation of bound and free 125I-hLH was achieved by adding sufficient 80% ammonium sulphate to yield a final concentration of 40% at 20°C, under which conditions antibody bound 125I-hLH was precipitated. The percentage binding of 1251-hLH to serial serum samples is shown in the table. At first there were high titres of a substance which cross-reacted with hLH, resulting in 32% binding compared with 50% for the positive control at a 1: 1000 dilution. There was a steady decline to undetectable binding at 1:1000 dilution within 2 years of the patient stopping taking posterior pituitary snuff. No substances capable of binding TSH or FSH were detected in the
patient’s serum. The results show evidence of anti-hLH antibodies in this
girl’s
after repeated insufflation of posterior pituitary snuff contaminated with porcine LH. The absence of TSH and FSH antibodies suggests that the immune response was directed against the &bgr;-subunit of LH, which, though not sharing major antigenic determinations with the subunit of TSH and FSH, is nevertheless not species specific. Hence the development of antibodies to human LH from antigenic stimulation with, in this instance, porcine LH. Similar results were obtained in a detailed study reported by Clements et al.,6 ofa prepubertal girl previously treated for diabetes insipidus with injections of pitressin tannate. Immunological studies indicated the presence of high-affinity 7S IgG antibodies directed against the &bgr;-subunit of LH. We report this case to re-emphasise the importance of not using partly purified protein preparations for chronic replacement serum
Department of Microbiology, Southampton General Hospital,
D. V. SEAL E. H. CUTHBERT
Southampton SO9 4XY
POSTERIOR PITUITARY EXTRACT AND LUTEINISING HORMONE ANTIBODIES
SIR.—We have seen a 6-year-old girl with cranial diabetes insipidus who acquired anti-human-LH (luteinising hormone) antibodies at high titre as a result of repeated treatment with
posterior pituitary snuff contaminated with porcine LH. She was referred for investigation of short stature. At age 2 she had presented with symptoms of diabetes insipidus; no cause was established. Posterior pituitary powder snuff administered as the contents of ’Di-sipidin’ capsules (Paines and Byrne Ltd) controlled her symptoms adequately. However, her growth velocity was only 3 cm/year (less than 3rd percentile). Serum thyroxine concentration was normal. Anterior pituitary function was assessed by a combined stimulation test;5 there was no growth hormone or thyroid stimulating hormone response, but cortisol and follicle-stimulating hormone responses were normal. Basal and peak serum LH concentrations, determined by double-antibody radioimmunoassay, were very high. Plasma oestradiol was normal for a prepubertal girl. Treatment for diabetes insipidus was changed to DDAVP (1-desamino-8D-arginine vasopressin; Ferring AB, Sweden) and during the ensuing year her growth velocity increased to 9.0 cm/year with thyroxine and growth replacement. The cause of the raised serum LH concentrations was further investigated. 1 Maskell R, Pead L, Allen L The puzzle of "urethral syndrome": a possible answer? Lancet 1979; i: 1058-59 2 Drabu YJ, Sanderson PJ. Urine culture in "urethral syndrome" Lancet 1980; i: 37-38. 3 Gargan RA, Brumfitt W. Hamilton-Miller JMT Do anaerobes cause urinary infection? Lancet 1980; i 37 4 Brumfitt W, Hamilton-Miller JMT, Ludlam H, Gooding A Lactobacilli do not cause frequency and dysuria syndrome Lancet 1981; ii: 393-96 5
Savage DCL, Swift PGF, Johnston PGB, Goldie DJ, Murphy anterior
pituitary function
in
children Arch Dis Child
1978,
D. Combined 53: 301-04
test
of
therapy, especially since highly purified or synthetic preparations, such as DDAVP, are readily available. of Child Health, Welsh National School of Medicine, Heath Park, Cardiff CF4 4XN
Department
Department of Clinical Chemistry, Southmead General Hospital, Bristol
I.A. HUGHES I. D. WARD D. J. GOLDIE
GAMMAGLOBULIN AGAINST HEPATITIS A
SIR,-I would like to make comment on your note on Immunisation for Travellers (Nov. 28, p. 1241). Your review of the Liverpool School of Tropical Medicine’s booklet states that supplies of gammaglobulin against hepatitis A are limited. The booklet refers only to supplies held by the Public Health Laboratory Service. I can assure you that there are adequate supplies of ’Gamma Globulin Kabi’ to meet all requirements in the U.K. KabiVitrum Ltd, Uxbridge, Middlesex UB8 2YF
6. Clements
I. DAINOW
JA, Faiman C, Paraskevas F, Reyes FI, Winter JSD Development of antitherapy with posterior pituitary extract J Clin Endocrinol
hLH antibodies after Metab 1978, 47: 1-8
DOUBTFUL SIGNIFICANCE OF FASTIDIOUS BACTERIURIA IN THE URETHRAL SYNDROME
PREPUBERTAL GIRL AFTER STOPPING THERAPY WITH DI-SIPIDIN
et
(POSTERIOR
a1.l
have implicated "fastidious" bacteria Lactobacillus and spp.) in the "urethral (Corynebacterium svndrome" (dysuria and frequency without "significant" bacteriuria). We have cultured fresh urine from three groups of women who were not on antibiotics. Midstream urines (MSUs) were collected for screening purposes from 100 symptom-free pregnant women. The uncentrifuged urine was cultured by the filterpaper foot impression method, able to detect 104 bacteria/ml, at 37°C for one day on MacConkey agar and for five days in 5% CO2 on chocolate agar. 14 samples grew "fastidious" bacteria-8 in pure culture, 5 mixed with Staphylo,coccus epidermidis, and 1 mixed with coliforms. Urine from 94 women without urinary symptoms, with an average age of 67, was collected aseptically at the time of preoperative catheterisation and similarly cultured. 3 samples grew fastidious bacteria as a pure culture (1 at 104/ml and 2 at whilst 1 sample produced a growth of mixed fastidious bacteria at
SIR,-Maskell
105/ml),
104/ml. MSUs collected from 100 women with dysuria, frequency, and pyuria (>10 per high-power field) and which gave no growth on MacConkey agar were cultured for fastidious bacteria. These were isolated from 5 samples at >104/ml, as pure growth. We have thus found a low isolation rate of fastidious bacteria (5%) in women with the urethral syndrome that compares with the isolation rate for women without symptoms either pregnant (8% pure) or postmenopausal (4%). Drabu and Sanderson2 found a similar rate (6%) in patients with the urethral syndrome whilst Gargan et al. grew fastidious bacteria fr m women with recurrent urinary infections both with and without ymptoms. Brumfitt et a1.4 found higher isolation rates of fastidious bacteria than we did, but they too found no significant difference between the rates in healthy women and in patients with dysuria and frequency.
*All values have had
PITUITARY POWDER
SNL’FF)
negative controls subtracted.
Blood was collected serially over 2 years and sera were stored at - 20°C until analysed. Rabbit anti-hLH serum and serum from a normal adult female acted as positive and negative controls respectively. Serial dilutions, of patient and control sera up to 1 :200 000 were made in 5 mmol/1 phosphate buffer, pH 7-5. Duplicate volumes of the dilutions were dispensed into polycarbonate tubes with 1251-hLH and phosphate buffer and incubated for 5 days at 4°C. Separation of bound and free 125I-hLH was achieved by adding sufficient 80% ammonium sulphate to yield a final concentration of 40% at 20°C, under which conditions antibody bound 125I-hLH was precipitated. The percentage binding of 1251-hLH to serial serum samples is shown in the table. At first there were high titres of a substance which cross-reacted with hLH, resulting in 32% binding compared with 50% for the positive control at a 1: 1000 dilution. There was a steady decline to undetectable binding at 1:1000 dilution within 2 years of the patient stopping taking posterior pituitary snuff. No substances capable of binding TSH or FSH were detected in the
patient’s serum. The results show evidence of anti-hLH antibodies in this
girl’s
after repeated insufflation of posterior pituitary snuff contaminated with porcine LH. The absence of TSH and FSH antibodies suggests that the immune response was directed against the &bgr;-subunit of LH, which, though not sharing major antigenic determinations with the subunit of TSH and FSH, is nevertheless not species specific. Hence the development of antibodies to human LH from antigenic stimulation with, in this instance, porcine LH. Similar results were obtained in a detailed study reported by Clements et al.,6 ofa prepubertal girl previously treated for diabetes insipidus with injections of pitressin tannate. Immunological studies indicated the presence of high-affinity 7S IgG antibodies directed against the &bgr;-subunit of LH. We report this case to re-emphasise the importance of not using partly purified protein preparations for chronic replacement serum
Department of Microbiology, Southampton General Hospital,
D. V. SEAL E. H. CUTHBERT
Southampton SO9 4XY
POSTERIOR PITUITARY EXTRACT AND LUTEINISING HORMONE ANTIBODIES
SIR.—We have seen a 6-year-old girl with cranial diabetes insipidus who acquired anti-human-LH (luteinising hormone) antibodies at high titre as a result of repeated treatment with
posterior pituitary snuff contaminated with porcine LH. She was referred for investigation of short stature. At age 2 she had presented with symptoms of diabetes insipidus; no cause was established. Posterior pituitary powder snuff administered as the contents of ’Di-sipidin’ capsules (Paines and Byrne Ltd) controlled her symptoms adequately. However, her growth velocity was only 3 cm/year (less than 3rd percentile). Serum thyroxine concentration was normal. Anterior pituitary function was assessed by a combined stimulation test;5 there was no growth hormone or thyroid stimulating hormone response, but cortisol and follicle-stimulating hormone responses were normal. Basal and peak serum LH concentrations, determined by double-antibody radioimmunoassay, were very high. Plasma oestradiol was normal for a prepubertal girl. Treatment for diabetes insipidus was changed to DDAVP (1-desamino-8D-arginine vasopressin; Ferring AB, Sweden) and during the ensuing year her growth velocity increased to 9.0 cm/year with thyroxine and growth replacement. The cause of the raised serum LH concentrations was further investigated. 1 Maskell R, Pead L, Allen L The puzzle of "urethral syndrome": a possible answer? Lancet 1979; i: 1058-59 2 Drabu YJ, Sanderson PJ. Urine culture in "urethral syndrome" Lancet 1980; i: 37-38. 3 Gargan RA, Brumfitt W. Hamilton-Miller JMT Do anaerobes cause urinary infection? Lancet 1980; i 37 4 Brumfitt W, Hamilton-Miller JMT, Ludlam H, Gooding A Lactobacilli do not cause frequency and dysuria syndrome Lancet 1981; ii: 393-96 5
Savage DCL, Swift PGF, Johnston PGB, Goldie DJ, Murphy anterior
pituitary function
in
children Arch Dis Child
1978,
D. Combined 53: 301-04
test
of
therapy, especially since highly purified or synthetic preparations, such as DDAVP, are readily available. of Child Health, Welsh National School of Medicine, Heath Park, Cardiff CF4 4XN
Department
Department of Clinical Chemistry, Southmead General Hospital, Bristol
I.A. HUGHES I. D. WARD D. J. GOLDIE
GAMMAGLOBULIN AGAINST HEPATITIS A
SIR,-I would like to make comment on your note on Immunisation for Travellers (Nov. 28, p. 1241). Your review of the Liverpool School of Tropical Medicine’s booklet states that supplies of gammaglobulin against hepatitis A are limited. The booklet refers only to supplies held by the Public Health Laboratory Service. I can assure you that there are adequate supplies of ’Gamma Globulin Kabi’ to meet all requirements in the U.K. KabiVitrum Ltd, Uxbridge, Middlesex UB8 2YF
6. Clements
I. DAINOW
JA, Faiman C, Paraskevas F, Reyes FI, Winter JSD Development of antitherapy with posterior pituitary extract J Clin Endocrinol
hLH antibodies after Metab 1978, 47: 1-8