HISTIOCYTIC MEDULLARY RETICULOSIS

204

prednisolone 5 mg daily, aspirin 600 mg twice daily, and indomethacin suppositories 100 mg at night. In January, 1979, ANA titre remained 1/640; DNA binding was 20 u/ml. IgM rheumatoid factor was still negative. In May 1979, the level of circulating immune complexes (measured by Clqbinding) was very high. In the following month, rheumatoid nodules developed around both elbows and smaller nodules were noted over the extensor aspects of her fingers. Rheumatoid factor was positive. X-ray of hands and feet showed synovial thickening and periarticular erosions. Hairy-cell leukaemia has lately been shown to be a B-cell proliferative disorder.3 We believe that this patient represents example of the association of autoimmunity with another B-cell disorders. M. A. J. CROFTS Department of Hæmatology, J. C. SHARP King’s College Hospital, Denmark Hill, London SE5 9RS

M. V. JOYNER

DIGOXIN AND HORMONE RECEPTORS et al. reported a lower recurrence-rate and abnormal morphology of breast cancer in women receiving "cardiac glycosides (mainly digoxin)," and LeWinn5 summarised other oestrogenic effects of digitalis. We have investigated the suggestion that digoxin interferes with oestrogen receptor (ER) on cytosols from eleven primary human breast carcinomas containing ER (mean 143 fmol/ml cytosol, range 46-304); the in-vitro binding of 3H-oestradiol6 0-9 nmol/1 was unaffected by 10 µmol/l digoxin. In the cytosol from two of these tumours, lower concentrations of digoxin (0.1, 1.0, 10, and 100 nmol/l, 1.0 µmol/l) also failed to compete with the binding of oestrogen to ER. Progesterone receptor (PgR) is another possible site of action of digoxin, especially since progesterone has been reported to bind to cardiac digoxin receptor.7 However, in cytosol from each of seven primary breast tumours containing PgR (mean 327 fmol/ml cytosol, range 92-740), digoxin at two concentrations (1-0 nmol/1 and 10 pnnol/1) did not interfere with the binding of the synthetic progesterone analogue R5020. The higher concentrations of digoxin used were considerably greater than the therapeutic range (0-65-2-60 nmol/1) and it is therefore unlikely that digoxin has any direct action on the binding of oestradiol of progesterone to their cytosol receptors in breast cancer in vivo. These results do not exclude the possibilities that digoxin exerts other direct effects on breast cancer or that one of the other cardiac glycosides competes for ER or PgR.

SIR,-Stenkvist

an

Department of Medicine, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2TH and Dudley Road Hospital, Birmingham

D.H. COVE G. A. BARKER

INTRATHECAL CYTARABINE IN MULTIPLE SCLEROSIS

SIR,—There is considerable interest in immunosuppressive in the management of multiple sclerosis (MS)8 and we wish to describe briefly our limited experience with intrathecal cytarabine. This agent has antiviral9 and immunosuppressant qualities--compatible with current notions concerning the possible aetiology of MS-and success has been claimed in the

therapy

3.

Jansen J, Schmit HRE, Van Zwet ThL, Meizer CJLM, Hijman W. Hairy Cell Leukæmia; A B Lymphocytic Disorder. Brit J Hæmat 1979; 42:

21-34. 4. Stenkvist B, Bengtsson E, Eridsson O, Holmquist J, Nordin B, WestmanNaeser S. Cardiac glycosides and breast cancer. Lancet 1979; i; 563. 5. LeWinn EB. Cardiac glycosides and breast cancer. Lancet 1979; i; 1196. 6. Woods KL, Cove DH, Howell A. Predictive classification of human breast carcinomas based on lactalbumin synthesis. Lancet 1977, ii; 14-15. 7. La Bella FS, Bihler I, Ki RS. Nature 1979; 278; 571. 8. Ellison GW, Myers LW. A review of systemic non-specific immunosuppressive treatment of multiple sclerosis. Neurology 1978; 28: 132-39. 9. Lanter CB, Bailey EJ, Lerner M. Assessment of cytosine arabinoside as an antiviral agent in humans. Antimicrob Ag Chemother 1974; 6: 598-602.

of progressive multifocal leucoencephalopathy,10-12 a disorder probably involving similar viral and immunological mechanisms. Since there are theoretical objections to systemic immunosuppression when the disease process is confined to the central nervous system and since intrathecal cytarabine has been used extensively and with safety in childhood leukxmia it seemed reasonable to use the intrathecal route. The project was approved by the ethics committee of University College Hospital and Medical School. Five patients with unequivocal disseminated sclerosis undergoing acute disabling exacerbations were invited to participate in a pilot study. One patient was subsequently rejected because we felt that the extent of his disease impaired his ability to understand the nature of the trial; the remainder gave their consent after detailed discussion. The regimen consisted of four intrathecal injections of 40 mg cytarabine in water 5 days apart. Patients were closely observed and progress was recorded; they were seen every week by an independent assessor. Three of the four patients failed to complete the course of treatment: two had signs of meningeal irritation and evidence of further neurological deterioration and the other experienced no meningism but continued to deteriorate. Only one patient completed the course without disturbance, but the pattern of the exacerbation showed no dramatic improvement. Following withdrawal from the trial, two of the three patients who had continued to deteriorate neurologically improved when given steroids. Two patients have been followed up for over a year and have experienced further relapses similar to the pre-treatment pattern of their disease. This pilot study was designed to determine the safety and possible efficacy of direct immunosuppression of the central nervous system in patients with MS. We report our disappointing experience in case others are considering a similar approach. While some of the meningeal reactions might be similar to those seen in patients with MS after diagnostic lumbar puncture, our clinical impression discourages us from offering this treatment to other patients. MARTIN GORE Department of Neurology, ROBERT BUCKMAN University College Hospital, London WC1 GERALD STERN treatment

HISTIOCYTIC MEDULLARY RETICULOSIS

SIR,-Schumacher and Stassl suggest that all cases of histiocytic medullary reticulosis (HMR) should be carefully investigated for viral, bacterial, or parasitic infections and carcinoma. They describe a case of apparent HMR associated with gastric carcinoma, and cases of HMR associated with viral infection2,3 and, possibly, with parasitic infection’ have been described. We support Schumacher and Stass’s suggestion. Two patients seen by us presented with an HMR-like illness due to a bacterial infection. Both had pyrexia, lymphadenopathy, hepatosplenomegaly, and pancytopenia. On bone-marrow aspiration there were sheets of bizarre, atypical histiocytes, many of which showed erythrocyte, granulocytic, and platelet phagocytosis. Subsequently both cases were shown to have typhoid fever and recovered fully on antibiotic treat10. Bauer

WR, Turel AP, Johnson JP. Progressive multifocal leucoencephaloand cytarabine: remission with treatment. JAMA 1973; 226:

pathy

174-76. 11. Marriott PJ, O’Brien MD, Mackenzie ICK, Janota IJ. "Progressive mulufocal lencoencephalopathy: remission with cytarabine". J Neurol Neurosurg Psychiat 1975; 38: 205-09. 12. Wiltshaw E, Buckman R. Progressive multifocal lencoencephalopathy successfully treated with cytosine arabinoside. Br J Hœmatol 1976, 34: 153-55. 1. Schumacher HR, Stass SA. Lancet 1979; i: 158-59. 2. Chandra P, Chaudhery SA, Rosner F, Kagan M. Transient histiocytosis with striking phagocytosis of platelets, leukocytes and erythrocytes. Arch In-

tern Med 1975; 135: 989-91. 3. Risdall R, McKenna R, Kriuit W, Nesbitt M, Brunning R. Virus associated hemophagocytic syndrome. Blood 1978; 52: suppl i, 272 (abstr). 4. Serck-Hanssen A, Purchit GP. Histiocytic medullary reticulosis. Br J Cancer

1968, 22: 506-16.

205 ment.

Repeat bone-marrow aspiration

on one

patient was nor-

TABLE I-FOLLOW-UP OF

URINARY/RECTAL CARRIAGE OF THE

RESISTANT KLEBSIELLA STRAIN AMONG PATIENTS IN THE

mal. Department of Hæmatology,

ISOLATION WARD

South African Institute

F. FERNANDES-COSTA I. EINTRACHT

for Medical Research, Johannesburg 2000, South Africa

CONTROL OF HOSPITAL EPIDEMIC OF GENTAMICIN-RESISTANT KLEBSIELLA AEROGENES an outbreak of infection by a K21 Klebsiella with transferable resistance strain of aerogenes

SIR,-In the spring of 1978

ampicillin, carbenicillin, sulphonamide, chloramphenicol, trimethoprim, tetracycline, streptomycin, gentamicin, and tobramycin occurred in seven wards (A-G) in one of our hospitals. As in similar outbreaks, patients often did not require chemotherapy. The acquisition of the strain was associated with catheterisation and the administration of antibiotics, especially ampicillin and co-trimoxazole (’Septrin’).1-3 Barrier nursing of colonised patients in cubicles was used as a means of the outbreak for the first eight weeks, but failed (see figure). More drastic measures were introduced on March to

1, and these were associated with

a

*

When the weekly result was negative, further specimens were examined within 2 days, and once again the following week. t 2 patients discharged home with two consecutive negative results. TABLE II—DETECTION BY SCREENING OF GENTAMICIN-RESISTANT

K.AEROGENES

substantial decrease in the

epidemic spread of the organism (see figure).

T

i estea in nrst

screening wnn negauve resuns.

t A positive patient moved out of isolation ward after three negative screening results. Four weekly rectal swabs after April 4 all negative.

Jan

5Feb 9 Mar 13 Apr 17 May 21 Jun 25 Jul

No. of week Pattern of epidemic. Establishment of isolation ward.-Rectal swabs and urine were examined at weekly intervals from all patients in the isolation ward (table i). Fit patients, whatever their carrier state, were discharged. Patients negative in three consecutive tests were moved out of the isolation ward. Detection of carriers.-Urine and rectal swabs from patients in the seven contaminated wards were examined for the epidemic strain (table n). All the carriers detected were moved to the isolation ward The contaminated wards were cleaned before being reopened for normal use. Antibiotic policy-Co-trimoxazole, ampicillin, and amoxycillin were used only when no suitable alternative antibiotic was available and usually after discussion with a member of the department of medical microbiology. None of these antibiotics was prescribed in the isolation ward except in one patient with Proteus wound infection.

, ’

trol. The isolation ward reduced the demand on nurses as well as the possibility of spread, but introduced some anxiety amongst patients, relatives, and some members of the hospital staff. Patients with long-termed carriage (table I), might well introduce the epidemic strain into the hospital on readmission, and this will make the attempt to eradicate the organism from the hospital more difficult. We recommend that detection of carriers and their segregation from uncolonised patients deserve a trial when barrier nursing of individual patients fails to prevent the spread of the organism. Our experience with the four uncolonised patients in the isolation ward supports the view that intelligent restriction of the use of antibiotics should be a serious consideration in controlling the epidemic spread of such organism.4,5 We thank all members of hospital staff and departments concerned Mile End Hospital, for their help, and Dr M. Casewell, St Thomas’ Hospital, London, for typing the Klebsiella strains and for the resistance-transfer experiment. at

ELIZABETH T. HOUANG MICHAEL A. L. EVANS CLARE N. SIMPSON

Department of Medical Microbiology, London Hospital Medical College, London E1 1BB

ASPIRIN AND BLEEDING-TIME

Four patients without the epidemic strain were admitted to the isolation ward in error. Three of them stayed in the ward for 4 weeks and remained negative throughout. The fourth pa tient became a rectal carrier at the fourth week but was subsequently negative and was discharged on the 6th week. It appears that even in a ward full of carriers, colonisation as detected by weekly examination of urine and a rectal swab does not occur readily. None of the four patients had been catheterised or given antibiotics. Detection of carriers and their segregation from non-carriers diminished the prevalence of the epidemic strain, thus providing a means to bringing the outbreak rapidly under con-

SIR,—Moncada1 reported a paradoxical effect of aspirin-at high doses aspirin did not prolong the bleeding-time. Godal et al. were unable to confirm this finding, and our experience does not support it either. Over the past twelve years we have investigated 9060 patients for possible clotting defects. We found 238 cases of haemophilia A, 44 of haemophilia B, 79 of von Willebrand’s disease, and 60 rare congenital defects (factor X Fruili, prothrombin deficiency, factor VII deficiency, and so on); about 1000 patients had other acquired disorders such as coumarin ther-

1. Casewell MW, Dalton MT, Webster M, Phillips I. Gentamicin-resistant Klebsiella œrogenes in a urological ward. Lancet 1977;ii:444-46. 2 Cune K, Speller DCE, Simpson RA, Stephens M, Cooke DI. A hospital epidemic caused by a gentamicin-resistant Klebsiella œrogenes. J Hyg Camb

5. Selden R, Lee S, Wang WLL, Bennett JV, Eickhoff TC. Nosocomial klebsiella infections: intestinal colonization as a reservoir. Ann Intern Med

1978; 80: 115-23. 3. Noble CJ, Down G, Chambers S, Dulake C, Mortimer PR, Palfreyman J. Klebsiella cross infection with capsular serotypes 68 and 21. Lancet 1979;i:832.

1. O’Grady J, Moncada S. Aspirin: a paradoxical effect on bleeding-time. Lancet 1978; ii: 780. 2. Godal HC, Eika C, Dybdahl JH, Dane L, Larsen S. Aspirin and bleedingtime. Lancet 1979;i: 1236.

4. Price

DJE, Sleigh JD. Control of infection neurosurgical unit by withdrawal

due of

Klebsiella œrogenes in a all antibiotics. Lancet

to

1970;ii:1213-15:

1971; 74: 657-64.