156 was isolated. On routine testing this found to be resistant to chloramphenicol and tetracycline, and the zone of inhibition round the penicillin disc (1-55 units) was reduced from the expected 10 mm to 7 mm, measured radially from the edge of the disc. By the agar dilution method, using a minimal-growth endpoint, the minimum inhibitory concentration (M.LC.) of penicillin was 0-25 {j.g/ml compared with an mt.i.c. of 0-03 g4nl for a sensitive strain. The M.i.c.s of tetracycline and chloramphenicol were both 20 g/ml. The inoculum used in these tests was about 106 organisms. Although this pneumococcus almost certainly was not indigenous to the U.K. its isolation makes it necessary for those treating serious pneumococcal disease to be aware that multiply resistant strains of the organism are close to, if not already on, our shores. A patient with a pneumococcal meningitis due to a strain with the M.i.c.s reported would be unlikely to respond adequately to treatment with penicillin’ or chloramphenicol.3 In respect of the treatment of such an infection we would add that its ampicillin M.i.c. was 0.15 ug/mi compared with 0.07 for a penicillin-sensitive strain; however, experience elsewhere3 has shown that much higher M.i.cs may be found. It has been said that testing pneumococci with high-concentration discs prevents the detection of significant penicillin resistance.4,5Although we use low-concentration discs, the zone of inhibition round an 8 unit tablet (’Neo-sensitabs’, A/S Rosco, Denmark) with the strain reported was reduced from a radius measured from the edge of the disc of 14 mm for a sensitive strain, to 10 mm.

23, Danish nomenclature)

was

We thank Dr M. T. Parker for

typing

the strain.

Public Health Laboratory Plymouth General Hospital, Plymouth PL4 8NN

TRIMETHOPRIM-RESISTANT KLEBSIELLA AEROGENES

SIR,-Reports trimethoprim-resistant coliforms1,2z a comparison of trimethoprim resistance among prompted Klebsiella aerogenes strains isolated from patients in hospital and from patients seen in general practice. Between Nov. 1, 1977, and April 30, 1978, 200 strains of K. aerogenes were isolated in our laboratory from first urine specimens-142 from hospital inpatients or patients recently discharged from hospital and 58 from patients in general practice or hospital outpatients. Sensitivity to trimethoprim was determined by agar dilution, plates of DST agar containing 2 fLg/ml being inoculated with 1:100 dilutions of an overnight broth culture by a Denley multipoint inoculator; a control plate with no antibiotic was also inoculated. The plates were incubated at 370C for 18-24 h. Resistance to trimethoprim was detected in 46 (32%) of the hospital strains but in only 4 (6%) of the general practice or outpatient strains. The higher resistance-rate in hospital patients may be due to the greater use of co-trimoxazole in hospitals in Ayrshire than in the community. of

Microbiology Department, Ayrshire Central Hospital, Irvine KA12 8SS

ROSEMARY E. T. MCGILL

THROMBOSIS AND FACTOR-IX CONCENTRATES

SIR,-The development of clinical evidence of deep-vein a 63-year-old man with therapeutic fibrinolytic

thrombosis in 4. 5. 1. 2.

Hansman, D., Devitt, L., Riley, I. Br. med J. 1973, iii, 405. Dixon, J. M. S. Lancet, 1974, ii, 474. Marks, P. J., Bruten, D. M., Speller, D. C. E. Lancet, 1977, ii, 774. Brumfitt, W., Hamilton-Miller, J. M. T., Grey, D. ibid. p 926.

blockade 5 days after a prostatectomy would not surprise the average surgeon. Whilst Dr Machin and Dr Miller’ were right to report the thrombotic complication in their patient with haemophilia B, they were wrong to assume a causal relationship between it and the administration of Oxford factor-ix concentrate. The use of this concentrate had converted their patient to a non-haemophilic state, and there is no reason to believe that in that state he would be any less prone to postoperative thrombosis than anyone else. Northern Regional Hæmophilia Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP

Service,

PETER

JONES

ENVIRONMENTAL DEPRIVATION AND ENRICHMENT IN COMA

SIR,-In considering what role synaptic reinnervation in recovery of function after brain damage Galbraith et al .2 correlated the rate of synaptic reinnervation in rats with the rate of recovery from coma due to head injury in man. The two recovery patterns, graphically illustrated by Galbraith et al., resemble patterns of other recuperative processes-most notably, in the context of brain function, that of the "catch-up phenomenon". They also resemble condensed forms of familiar, normal patterns of developmental processes from birth to maturity. Both recovery and developmental processes are highly susceptible to environmental factors. The effects of enriched or impoverished environments on maturation and development of the intact young brain have been reviewed elsewhere.4 In the intact adult sensory deprivation soon causes widespread impairment of intellectual and perceptual processes accompanied by changes in cerebral electrical activity.5 When the brain has been physically injured we can draw on experience with adult rats experimentally brain damaged at birth, from which Schwartz6 concluded "... that the deleterious effects of neonatal brain damage can be significantly offset by an enriched environment". In the comatose patient, although the problem is primarily cerebral and only secondarily related to the surroundings, there is, in effect, a state of environmental deprivation. Even the stimuli provided by the early hours and days of the emergency and by intensive treatment and repeated neurological examinations are not sufficiently strong, frequent, or persistent to compensate for severe sensory impairments. Nevertheless, the rate and degree of recovery from coma, and, probably, of synaptic reinnervation, can often be importantly enhanced. At the Institutes for the Achievement of Human Potential (I.A.H.P.) experiments started before 1955 with intensively enriched environments in comatose children progressed so that by 1965 coma treatment procedures were sufficiently developed and results impressive enough to warrant organisation of a special coma team. The team designs and applies orderly and systematic I.A.H.P. programmes of environmental inputs through all five sensory pathways, at a frequency, intensity, and duration far above those in the usual hospital, institutional, or home environment. We present here a preliminary report of the first pilot study of these I.A.H.P. procedures in sixteen consecutive patients in severe coma, admitted to hospitals in Nassau County, N. W., unaffiliated to I.A.H.P. The study was done independently by one of us (M.D.D.) who is also unattached to I.A.H.P. All functional evaluations of patients were made on the Glasgow

might play

1. Machin, S J , Miller, B. R. Lancet, 1978, i, 1367. 2. Galbraith, S., Jennett, B., Raisman, G. Lancet, 1978, i, 710. 3. Tanner, J. M. Child Devel. 1973, 34, 817. 4. LeWinn, E. B. Human Neurological Organisation, Springfield, 1969. 5. Zubek, J. P., Wilgosh, L. Science, 1973, 140, 306. 6. Schwartz, S. J. comp. Physiol. Psychol. 1964, 57, 72.

Illinois,

157

responsiveness scalean improved, less cumbersome, and more practical instrument for coma measurement than others. All patients were grade 3, 4, or 5 on the scale. They ranged in age from 4 to 80 years (mean 22). Coma was secondary to head injury in ten patients, hypoxia in four, and brain tumour, with prolonged postoperative unconsciousness, in two. All coma or

diagnoses were supported by angiography and/or computerised tomographic scanning. Patients with traumatic, acute epidural, subdural, or intracerebral hxmorrhage were excluded from the series. The first neurological examinations were done within 6 h of onset of coma and repeated daily. I.A.H.P. environmental enrichment programmes were started 12-24 h after admission to hospital, except in the two postoperative brain-tumour patients whose programmes started 10 and 14 days after surgery. Follow-up has ranged from several days to 10 months. There have been no deaths. All sixteen patients have fully recovered -from coma. Of twelve patients who have regained functional independence and are home, eight have reaquired their premorbid condition and have no detectable deficit. The other four, although still displaying some focal physical deficit or adaptive behaviour disorder, are recovering progressively. One patient, more recently admitted, is still in hospital. Two others, though alert, are in other institutions because of severe physical handicaps and lack of family to care for them. Of a comparable group of fourteen consecutive patients, also in severe coma (all grade 3-5 on the Glasgow scale), admitted to hospital during the previous 12-month period and followed up by one of us (M.D.D.), but not given programmes of environmental enrichment, eleven died (79%). The improved outcome in the I.A.H.P.-managed warrants continuation of this study.

EFFECT OF PHOTOTHERAPY ON SISTER CHROMATID EXCHANGE IN PREMATURE INFANTS first described in 1958,1 is now the method for reducing serum-bilirubin levels in jaundiced infants. Few clinically adverse side-effects directly due to phototherapy have been reported.2,3However, photosensitised damage of nucleic acids and proteins has been described in a number of biological systems.4 While no mutagenic effects of phototherapy have been detected on conventional chromosome analysis,5 Goyanes-Villaescusa et a1.6 concluded that phototherapy does increase the frequency of sister chromatid exchange (S.C.E.) in human lymphocyte chromosomes. s.c.E. induction, simply detected by bromodeoxyuridine-dye techniques,’8 is, in turn, considered to be a sensitive index of mutagen-carcinogeti exposure.8-1O However, s.c.E. analyses in our laboratory do not support the contention that phototherapy or in-vitro exposure of cells to bilirubin plus

SIR,-Phototherapy,

most common

light significantly

increase

lymphocyte

frequencies."

s.c.E.

TABLE I-EFFECT OF PHOTOTHERAPY ON S.C.E. LYMPHOCYTES FROM PREMATURE INFANTS

FREQUENCIES

IN

(S.C.E./CELL)

This letter condenses two papers-The Child in Coma (E.B.L.) and Coma recovery (M.D.D.)-presented to the llth annual meeting of the World Organisation for Human Potential, cosponsored by the National Aeronautics and Space Administration/Ames Research Center and the Institutes for the Achievement of Human Potential, at Moffett Field, California, on May 18,1978. Institutes for the Achievement

of Human Potential,

Philadelphia, Pennsylvania 19118,

U.S.A.

Neurological Surgery and Neurology, Freeport, N.Y.

EDWARD B. LEWINN

MIHAI D.

DIMANCESCU

* 29-35weeks of gestation. t Mean+ s.E.M. (and no. of cells). t Mean+ s.E. of the individual sample means. § Post-treatment values.

PROSTAGLANDIN-SYNTHESIS INHIBITORS IN PROPHYLAXIS OF FOOD INTOLERANCE

SiR,—I have had total lactose intolerance for the past twenty years. After reading the article by Dr Buisseret and his colleagues,’ I took 975 mg aspirin followed, twenty minutes later, by a heavy dairy meal consisting of a pint of ice cream, two glasses of milk, half a pound of Swiss cheese, and two ounces of butter. There were none of the customary immediate or delayed symptoms of malabsorption (borborygmi, cramps,

diarrhoea, tenesmus). The next test again followed 975 mg aspirin, and consisted of two large slices of chocolate cheese cake. Again I was free of retaliatory symptoms. I have subsequently conducted over twenty challenges, all with favourable results. My experience supports the success of Buisseret et al. with, among others, a lactose malabsorber in whom aspirin prevented symptoms after ingestion of 100 ml of cream. Department of Psychiatry, School of Medicine, Yale University, New

Haven, Connecticut 06510, U.S.A.

6. Jennett, B., Teasdale, G. Lancet, 1977, i, 878. 1. Buisseret, P. D., Youlten, L. J. F., Heinzelmann, D. I.,

1978, i, 906.

JULIAN LIEB Lessof,

F. H. Lancet,

Fifteen infants 880-1950 g, less than 58 h old, with bilirubin levels of 3-10 mg/dl, and not critically ill-were selected at random on admission to the neonatal intensive-care unit at the Boston Hospital for Women. 1 ml peripheral blood was obtained before and after 24-48 h of continuous phototherapy in a ’Narco Isolette’ phototherapy unit (Narco Medical Co.,

Warminister, Pennsylvania) containing

8

new

’Sylvania Day-

light’ bulbs (F20T12-D) set 24 cm above the infant. The incidental light energy from this apparatus, measured by chemical actinometry12 was approximately 600 W;cm2, calculated for a wavelength of 490 nm. Two blood-samples 24-48 h apart were obtained from control infants (not undergoing phototherCremer, R. J., Perryman, P. W., Richards, D. H., Lancet, 1958, i, 1094. Behrman, R. E., and others, J. Pediat. 1974, 84. 135. Wu, P. Y. K. in Phototherapy in the Newborn (edited by Odell and others); p.150. National Academy of Science, Washington, D.C., 1974. 4. Foote, C. S. ibid, p. 21. 5. Sandor, G. Lancet, 1973, 1, 1384. 6. Goyanes-Villaescusa, V. J., Ugarte, M., Vazues, A. ibid. 1977, ii, 1084. 7. Latt, S. A. Proc. Nat, Acad. Sci. U.S.A. 1973, 70, 3395. 8. Perry, P., Wolff, S. Nature, 1974, 251, 156. 9. Latt, S. A. Proc. nat, Acad. Sci. U.S.A. 1974, 71, 4162. 10. Perry, P., Evans, H. J. Nature, 1975, 258, 121. 11. Carrano, A. B., and others, ibid. 1978, 271, 551. 12. Hatchard, C. G., Parker, C. A. Proc. R. Soc. A. 1956, 235, 518. 1. 2. 3.

Environmental deprivation and enrichment in coma.

156 was isolated. On routine testing this found to be resistant to chloramphenicol and tetracycline, and the zone of inhibition round the penicillin d...
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