STAPHYLOCOCCUS EPIDERMIDIS INFECTIONS IN ACUTE MYELOBLASTIC LEUKAEMIA PATIENTS FITTED WITH HICKMAN CATHETERS

STAPHYLOCOCCUS EPIDERMIDIS INFECTIONS IN ACUTE MYELOBLASTIC LEUKAEMIA PATIENTS FITTED WITH HICKMAN CATHETERS

1191 ENHANCEMENT OF HUMAN IMPLANTATION BY EXOGENOUS CHORIONIC GONADOTROPIN SIR,-The efficiency of human fertilisation, both natural’ and in about 85%...

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1191 ENHANCEMENT OF HUMAN IMPLANTATION BY EXOGENOUS CHORIONIC GONADOTROPIN

SIR,-The efficiency of human fertilisation, both natural’ and in about 85%. However, the probability of conception,

vitro,2 is

recognisable by the absence of menses (recognisable fecundability rate), is only 0 -20-0’25 for women under the age of 30.1°3 This difference suggests that implantation of the fertilised ovum is the rate-limiting step in human fertility. An observation by Lenton et al,4 that serum progesterone levels during days 3-8 of the luteal phase were higher in conception cycles than in non-conception cycles, led us to investigate the possibility of enhancing implantation and recognisable fecundability by stimulating corpus luteum function with exogenous human chorionic gonadotropin

(hCG). Women with primary infertility who were receiving artificial insemination with donor sperm (AID) because their husbands were azoospermic or severely oligospermic volunteered for this study. We chose these women because ovulation and tubal patency had been proven and we could control the timing of insemination. A randomised, double-blind controlled study was done at two university centres with established artificial insemination programmes. Most patients received two inseminations with fresh donor sperm coinciding with days 11 and 13 of an ideal, 28-day cycle. From 3 days after the second insemination until the onset of menses or until pregnancy was confirmed by ultrasound, they were given an intramuscular injection three times a week (Monday, Wednesday, and Friday) from numbered but otherwise unlabelled vials containing, at random, either hCG(APL, Ayerst; 1000 IU per injection) or physiological saline randomly distributed with a random number table. We have completed 74 study cycles during which 15 pregnancies were achieved. In 35 saline-treated cycles 3 pregnancies occurred (a recognisable fecundability rate of 0 - 09), while in 39 hCG-treated cycles 12 pregnancies occurred (a rate of 0 -. 31) (x2 5 -37, p = 0 -02; Cochran’s modification ofx=4-33, p<0 05). In the 27 cycles in which hCG was administered but pregnancy did not occur, the luteal phase was prolonged by a mean±SEM of 4 -4±0 - 7 days in 11 cycles, but menses were not delayed in 16 cycles. There were 2 spontaneous abortions in the hCG-treated group. It is unclear why recognisable fecundability in the control group is slightly lower than that generally reported for women receiving AID (0-12-018507) but the randomised study design makes the increase m pregnancies in the hCG-treated group all the more striking in =

comparison. It is conceivable that, under normal conditions, hCG production by the early blastocyst that is sufficient to rescue the corpus luteum could occasionally be delayed, resulting in the onset of menses and loss of the pregnancy before recognition. Our findings suggest that it may be possible to increase the rate of implantation by supporting the corpus luteum with exogenous hCG until the implanting blastocyst can subserve this function independently. Alternatively,8 endometrial changes which result from progesterone elevation8 may favour implantation, and we also need to explore the effects of exogenous progesterone administration during the luteal phase on 1 London H. Human fertility: the basic components Chicago University of Chicago Press, 1977. 2 Trounson AO, Mohr LR, Wood C, Leeton JF. Effect of delayed insemination on invitro fertilization, culture and transfer of human embryos.J Reprod Fertil 1982; 64: 285-94 3 Bongaarts J A method for the estimation of fecundability. Demography 1975; 12: 645-60 4 Lenton EA, Sulaiman R, Sobowale O, Cooke ID. The human menstrual cycle: plasma concentrations of prolactin, LH, FSH, oestradiol and progesterone in conceiving and non-conceiving women. J Reprod Fertil 1982, 65: 131-39 5 Katzorke T, Propping D, Tauber PF. Results of donor artificial insemination(AID)in 415 couples. Int J Fertil 1981; 26: 260-66 6 Albrecht BH, Cramer D, Schiff I. Factors influencing the success of artificial insemination. Fertill Steril 1982; 37: 792-97. 7 Hanson FW, Overstreet JW, Katz DJ. A study of the relationship of motile sperm numbers in cervical mucus 48 hours after artificial insemination with subsequent fertility. AmJ Obstet Gynecol 1982; 143: 85-90. 8. Kreitman-Gimbal B, Bayard F, Hodgen GD. Changing ratios of nuclear estrone to estradiol binding in endometrium at implantation. Regulation by chorionic gonadotropin and progesterone during rescue of the primate corpus luteum. J Clin Endocrinol Metab 1981; 52: 133-37.

recognisable fecundability. In either case, since onset of menses was delayed in less than half of the hCG-treated cycles not resulting in pregnancy, the dosage of hCG used in this study may have been borderline, and a larger dose which consistently prolongs luteal function may be associated with still higher pregnancy rates. In view of the emotional (and financial) impact of the repeated attempts at artificial insemination and in vitro fertilisation required to achieve a pregnancy, a method that enhances fecundability could prove important. Our results may also have potential value in the treatment of "idiopathic" infertility in apparently normal couples. This work

was

supported by the

Medical Research Council of Canada.

Departments of Obstetrics and Gynaecology and Biophysics and Physiology, Dalhousie University, Halifax, Nova Scotia, Canada, B3H 1W3

Department of Obstetrics and Gynaecology, University of Western Ontario, London, Ontario

ROBERT F. CASPER ELAINE WILSON JOHN A. COLLINS

STANLEY E. BROWN PARKER

JANE ANN

STAPHYLOCOCCUS EPIDERMIDIS INFECTIONS IN ACUTE MYELOBLASTIC LEUKAEMIA PATIENTS FITTED WITH HICKMAN CATHETERS

SIR,-An increased incidence of Staphylococcus epidermidis infections in granulocytopenic patients has been described in reportsl°2 from Los Angeles and Baltimore. The emergence of this usually non-pathogenic microorganism as a cause of infection in been to has related immunocompromised patients and the use of Hickman catheters. However, granulocytopenia there is disagreement about the role of long-term indwelling catheters to explain the recent increase in the incidence of infections caused by S epidermidis. Our experience may help to clarify this issue. Between September, 1982, and September, 1983, we implanted 34 Hickman catheters to 34 patients with acute myeloblastic leukaemia (AML) admitted for intensive chemotherapy3(28 for induction remission at diagnosis, 5 in relapse, and 1 for late intensification in remission). Sixty episodes of granulocytopenia were recorded in patients while the catheters were in place. Oral antibiotics or other preventive techniques (eg, granulocyte transfusions and laminar air flow rooms) were not used. The daily care of the catheter was provided by the patient’s primary nurse, following Hickman and colleagues’ guidelines.Empirical broad-spectrum antibiotics therapy with carbenicillin plus amikacin was given to all granulocytopenic patients in whom fever developed. Vancomycin was added when a S epidermidis infection was diagnosed or strongly

suspected (exit site or tunnel infection). Forty-nine microorganisms were isolated in thirty episodes of bacteraemia in 23 patients with chemotherapy associated granulocytopenia. The commonest was S epidermidis (alone in twelve and in association with other organisms in six episodes). S epidermidis bacteraemia was considered clinically significant in only nine of these eighteen episodes. Exit site infections were observed eight times in 8 patients, but only five were bacteriologically confirmed (2 S epidermidis, 2 S epidermidis plus Corynebacterium spp, and 1 P aeruginosa). 7 out of these 8 patients acquired bacteraemia. In 4 patients the same microorganism was grown from both sites (2 Sepidermidis, 1 Corynebacterium spp, and 1 P aeruginosa). 1. Winston

DJ, Dudnick DV, Chapin M, Ho WG, Gale RP, Martin WJ. Coagulasenegative staphylococcal bacteremia in patients receiving immunosuppresive therapy. Arch Intern Med 1983; 143: 32-36. 2. Wade JC, Schimpff SC, Newman K, Wiernick PH. Staphylococcus epidermidis an increasing cause of infection in patients with granulocytopenia. Ann Intern Med 1982; 97: 503-08 3. Sanz M, Gonzalez M, Besalduch J, Martinez J, Rafecas J, Martin G, Marty ML Prolonged remission maintenance in ANLL with intensive sequential combination chemotherapy. 3rd International Symposium on Therapy of Acute Leukemias. (Rome, 1982): abstr 365 4. Hickman RO, Buckner D, Clift RA, Sanders JE, Stewart P, Thomas ED. A modified right atrial catheter for access to the venous system in marrow transplant recipients. Surg Gynecol Obstet 1979; 148: 871-75

1192 These results were compared with infections identified among AML cases recorded prospectively since June, 19775(see table). There has been a remarkable increase in the incidence of bacteraemia due to S epidermidis since September, 1982, when the Hickman catheter insertion became routine in AML patients. No other changes in management (eg, in chemotherapy, antibiotic therapy, prophylaxis of infection) were introduced during this period.

lobe (fig 1). "C-methionine imaging with PET 45 demonstrated very high radioactivity in the tumour (fig 2), the image being clearer and more contrasted than that obtained with galhum-67. The patient’s subsequent clinical course and cytological examination confirmed recurrence of squamous cell carcinoma of the lung.

MICROORGANISMS ISOLATED FROM BLOOD IN AML PATIENTS

Fig I-Chest computerised tomographic scan showing lung tumour and giving anatomical reference for PET image.

In the light of this experience we think that Hickman catheters be considered as a source of S epidermidis infection in AML patients under intensive chemotherapy. Reinforcement of catheter care education to the patient and his family and to nurses and doctors and the early use of antistaphylococcal antibiotics (probably, the first choice is intravenous vancomycin) when a S epidermidis infection is suspected could diminish morbidity and mortality in AML patients with a Hickman catheter. must

Haematology, Cardiovascular Surgery, and Microbiology Services, Cludad Sanitaria de la Seguridad Social Valencia 9, Spain

"La Fe",

MIGUEL A. SANZ MIGUEL SUCH F. JAVIER RAFECAS GUILLERMO MARTIN MARIA SANTOS

CANCER DIAGNOSIS WITH POSITRON COMPUTED TOMOGRAPHY AND CARBON-11-LABELLED L-METHIONINE

SIR,-Tumour imaging with 75Se-selenomethionine has been studied in lung cancerand other tumours2 but its diagnostic value is limited by high background activity and poor resolution. Positron emission computed tomography (PET) with "C-labelled methionine is of diagnostic value for pancreas diseasebut has not been applied to tumour scanning. In the lung cancer patient described here scanning with PET using 11 C-L-methionine produced a clearer picture than did conventional gallium-67

scintigraphy. A 69-year-old man with a history of lung squamous carcinoma and radiotherapy was admitted in May, 1983, with chest pain and cough. A chest X-ray revealed a new shadow in right upper lobe partly masked by radiation fibrosis. Whole body scanning and chest scintigraphy (gallium-67 citrate) showed "hot" lesions bilaterally in the pulmonary hilus and faint radioactivity in the right upper lobe. A computerised tomographic scan revealed small lymph nodes in the pulmonary hilus (unchanged from 6 months previously) and a 2’ 5 x 3 cm solid tumour attached to mediastinum in the right upper 5. Rafecas

FJ, Martin-Aragones G, Sanz MA, Martinez JA, Perez-Belles C, Santos M, Gobernado M, Marty ML. Bacteremia in granulocytopenic patients 7th meeting of

International Society of Haematology European and African Division (Barcelona, 1983) abstr 702. 1. Critchley M, Testa HJ, Stretton TB. Combined use of 99mTechnetium-labelled macroaggregates of albumin and "Selenium-sclenomethionine in the diagnosis of lung cancer. Thorax 1974, 29: 421-24. 2 Bose A, Tanaka T, Mishkin F. Selenomethionine uptake in the thorax Semm Nucl Med 1982; 12: 220-21. 3. Syrota A, Duquesnoy N, Kellershohn C The role of positron emission tomography in the detection of pancreatic disease. Radiology 1982, 143: 249-53.

Fig 2-Lung tumour image with PET (’ECAT IT99 Ortec) 40 min after injection of7 mCi of’C-L-methionine. Count

ratios

per

pixel at 40

mm were

tumour/aorta 2-8,

tumour/lung 7-5,

1. tumour/muscle 4 °

Selenium-75 has a long half-life (128 days) so the injected dose be small (250 flC1 or so) while the use of aminoacids labelled with carbon-11permits injection of large doses because of the short half-life (20.44 min). Furthermore, molecules labelled with carbon-11 retain their natural configuration and are thought to be incorporated into protein.The tumour images obtained by 11C-methionine can be assessed as increased rate of protein synthesis.The use of PET with improved detection mdependent of depth, should greatly increase the diagnostic value of 11 C-methionine.’’ C-methionine is taken up by normal organs (such as liver and pancreas) as well as tumour but not by heart unpublished). It is reported to leave the blood pool rapidly.4 Thus, 1 C-methionine may be an effective marker for increased ammoacid metabolism of tumour in mediastinum and lung. must

We thank Mr S. Itagaki for technical assistance. Supported by a grant-m-aid for scientific research 00544052, Ministry of Education, Science and Culture,

Japan. Department of Radiology and Nuclear Medicine, Research Institute for Tuberculosis and Cancer, Tohoku University,

Senda 980, Japan, and Cyclotron and Radioisotope Centre, Tohoku University

K. KUBOTA M. ITO H. FUKUDA Y. ABE K. ITO T. FUJIWARA S. YOSHIOKA J. HATAZAWAT. MATSUZAWA R. IWATA S. WATANUKI K. ISHIWATA T. IDO

-

4 Comar

5.

D, Cartron JC, Maziere M, Marazano C Labelling and metabolism of

methionine-methyl-11C Eur JNucl Med 1976, 1: 11-14 Fukuda H, Matsuzawa T, Abe Y, et al Experimental study for cancer diagnosis with positron-labelled fluorinated glucose analog 15F-2-fluolo-2-deoxy-D-mannose a for cancer detection Eur J Nucl Med 1982, 7: 294-97 H, Davis JR. Honig GR, Anderson DC, Nair PV, Nyhan WL The uptake of a

new tracer

6 Bush

variety of amino acids 1959, 19: 1030-39

into

nuclear proteins of tumors and other

tissues

Cancer Res