286 We thank the World Health Organisation (Human Reproduction Unit), Geneva and the Population Council (New York) for financial support for this study. Departments of Chemical Pathology and Hæmatology, University of Ibadan, Nigeria.

D. A. OLATUNBOSUN W. A. ISAACS-SODEYE F. A. ADENIYI B. K. ADADEVOH.

Tk-POLYAGGLUTINATION IN BACTEROIDES FRAGILIS SEPTICÆMIA

SiR,—Tk-polyagglutination was first described by Bird Wingham.1 Tk erythrocytes are agglutinated by an extract of peanuts (Arachis hypogaea) but are distinguished from T-transformed erythrocytes by the fact that their sialic-acid levels are normal, and by various other properand

ties.1

Subsequently, a patient was studied2 whose erythrocytes showed both T and Tk polyagglutination. Escherichia coli, Clostridium welchii, and Bacteroides fragilis were isolated from an infected surgical incision, but not from blood-cultures. Investigation showed that B. fragilis was probably responsible for the erythrocyte change. Detailed in-vitro studies of the role of B. fragilis in the production of erythrocyte polyagglutination are in progress and will be presented elsewhere. Our purpose here is to record that we have investigated a patient with Bacteroides fragilis septicaemia whose erythrocytes were found to be Tk-polyagglutinable. This provided a clear demonstration that this organism is definitely a cause of this condition. Its precise mode of action is under investigation. Regional Blood Transfusion Service, Vincent Drive, Birmingham B15 2SG.

Regional Blood Transfusion Service, Carluke.

Bacteriology Department, Law Hospital, Carluke.

G. W. G. BIRD JUNE WINGHAM.

Department of Medical Microbiology, University Hospital, Sölvegatan, S-223 62 Lund, Sweden.

G. KAHLMETER C. KAMME.

G. INGLIS. A. A. B. MITCHELL.

PROLONGED EXCRETION OF GENTAMICIN IN A PATIENT WITH UNIMPAIRED RENAL FUNCTION SIR,-Gentamicin is excreted almost entirely by glomerular filtration, and in patients with normal renal function 100% of the drug is said to be excreted in the urine within 24 hours.3,4 However, in urasmic patients the drug can be detected in serum and in urine for more than a week after the last dose. We have seen a patient with normal renal function who excreted gentamicin for 20 days after therapy had been discontinued. The patient was a 22-month-old boy with a severe organic heart defect. He was physically retarded with a body weight of 6-9 kg. He was treated with digitalis and diuretics. He had no signs of renal impairment, and at no time did his serum-creatinine exceed 30 µmol per litre. Over a period of 8 days he was treated with intramuscular (i.m.) injections of 8 mg. gentamicin three times a day (3-5 mg. per kg. per day). No other antibiotic was given. The peak serum level occurred 1-2 hours after an injection and never rose above 2-0 µg. per ml. Only 25-30% of the daily dose could be recovered in the urine. After therapy was discontinued, measurable concentrations Bird, G. W. G., Wingham, J. Br. J. Hœmat. 1972, 23, 759. Inglis, G., Bird, G. W. G., Mitchell, A. A. B., Milne, G. R., Wingham, J. Vox. Sang. (in the press). 3. Black, J., Calesnick, B., Williams, D., Weinstein, M. J. Antimicrob. Ag. Chemother. 1963, 3, 138. 4. Gingell, J. C., Chisholm, G. D., Calnan, J. S., Waterworth, P. M. J. infect. Dis. 1969, 119, 396. 5. Milman, N. Ugeskr. Laeg. 1973, 135, 1861.

1. 2.

(>_02 µg. per ml.) were found in the serum for 8 days, falling from 0-8 µg. per ml. on the first two days after therapy to 02 µg. per ml. on the 8th day. In the urine gentamicin could be detected for up to 20 days: 7-8 µg. per ml. on the first two days, falling to about 0.2 tLg. per ml. on the 20th day. From the 2nd to the 20th day after therapy approximately 15 mg. gentamicin was recovered in the urine (i.e., nearly 8% of the total dose). The assays were carried out by agar-well diffusion. When adding anti-gentamicin antiserum 6 to the urine no zones of inhibition were obtained. The specificity of the assays was further checked by determining serum and urine concentrations with a radioimmunological technique.6 The low recovery during therapy and the prolonged excretion after the last dose point to accumulation of the drug followed by a slow release. Red blood-cells may have the capacity to take up gentamicin and thus influence the pharmacokinetic properties of the drug: in patients with high haematocrit low and sustained serum levels were found.’ This suggestion would fit our case since the serum levels during therapy were unexpectedly low and his hæmatocrit was 57-60%. However, in-vitro tests with fresh cells from the patient and blood-donors provided no evidence of uptake of gentamicin by red blood-cells. An investigation now in progress indicates that an accumulation of gentamicin often occurs in patients on i.m. therapy, followed by a slow release of the drug. Perhaps our patient represents a rule rather than an exception. Other tissues than erythrocytes seem to bind the drug. Perhaps some i.m. gentamicin is taken up at the site of injection, and repeated injections at the same site may enhance uptake.

THYROTROPHIN-RELEASING HORMONE IN DEPRESSION were reported by Dr Coppen and results SIR,—Negative his colleagues (Aug. 24, p. 433) with thyrotrophin-releasing hormone in the treatment of depression. In their first trial, Hamilton’s rating scale was applied at 3-hourly intervals and later at 6-hourly and 12-hourly intervals as the only measure of change. In the second trial the Hamilton rating scale

was applied twice weekly 2-hourly for the first 6 hours.

and the 100

mm.

line test

We submit that the authors have misused the Hamilton to measure short-term change with it. It was devised to record the severity of symptoms rather than minor fluctuations; and Hamilton instructs8 that,questioning on all items should be directed to the patients’ condition in the past few days or week. Items concerned with insomnia (items 4, 5, 6), time spent in work activity (7), loss of libido (14), and loss of weight (16) are obvious examples of symptoms that would not fluctuate in 3 hours. The objective of the first trial has been missed by using a measure that is not sensitive to rapid improvement, though on the second trial the measures are more appropriately

rating scale by attempting

applied. A point frequently overlooked is that the success of a well-designed drug trial lies ultimately in the sensitivity of the instruments selected to evaluate change. Department of Psychiatry, Groote Schuur Hospital, Observatory, Cape,

Republic of South Africa. 6. 7. 8.

D. SMART P. J. V. BEUMONT G. C. W. GEORGE.

Jonsson, S., Karlmeter, G., Hallberg, T., Kronvall, G. Unpublished. Riff, L. J., Jackson, G. G. J. infect. Dis. 1971, 124, S98. Hamilton, M. Br. J. soc. clin. Psychol. 1967, 6, 278.

Letter: Thyrotrophin-releasing hormone in depression.

286 We thank the World Health Organisation (Human Reproduction Unit), Geneva and the Population Council (New York) for financial support for this stud...
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