ALCOHOL FLUSHING AND PROSTAGLANDINS

935 "details of techniques used, including the size of the inoculum". However, this international study does not provide specific recommendations about sensitivity testing for H. influenza. Bell and Plowman used an inoculum size of "104 organisms per replicator drop (4 1)" which equals 2.5 x 106 colony-forming units/ml. This is much too large an inoculum, and can produce marked differences in MIC values. The collaborative study recognised this problem with p-lactamase-producing staphylococci; thus they cautioned (p. 43) that "Penicillinase-producing staphylococci give rise to special and important problems in susceptibility testing with this penicillinase-susceptible penicillin [ampicillin]. Comparatively small differences in size of inoculum may result in marked differences in MIC values." Furthermore, Thornsberry and Kirven2 showed that an inoculum size of 104 cfu/ml of H. injiuenzce should be used for antibiotic sensitivity testing to determine reproducibly the susceptibility of H. influenzae to ampicillin. When the inoculum size was increased, an "increase in MIC of ampicillin for either susceptible or resistant strains" was observed. Also, Turk,’ studying 25 ampicillin-sensitive strains of H. !K/7MeM.s, showed that after 24 h incubation all strains were sensitive to ampicillin when small inocula (104 cfu/ml) were used, while 16 of 25 strains still grew at 5 mg/1 when large inocula (107 cfu/ml) were tested. These data suggest that the high incidence of non-&bgr;-Iactamase producing ampicillin-resistant H. influenzce strains reported by Bell and Plowman is, in part, the result of their usage of the larger inoculum. In addition, these workers used 1 mg/1 ampicillin as the dividing point between sensitive and resistant: it is customary to use a 2 mg/l, the concentration recommended by the International Collaborative Study (p.

the presence of (3-lactamase in more than 50% of the strains which they consider to be ampicillin-resistant.

arrived continuous rectal temperature recordOnce the patient’s temperature had fallen to 100°F treatment was discontinued and the patient was wrapped in warm blankets to encourage sweating. The temperature always fell by at least another degree after this. If the patient was conscious, plentiful warm oral fluids were given and an indwelling catheter was passed. The passing of urine was the turning point in the patient’s recovery. Except in a few cases which would probably not have responded to any treatment, this routine was dramatically effective but posed two problems. The first was to ensure that the pyrexia really was the result of heat exposure. Two patients, to my knowledge, were treated at heatstroke centres when, in fact, they had pneumonia. The second was the problem raised by Professor Weiner and Dr Khogali (March 8, p. 507)-namely, the discomfort experienced by the patient during the treatment. The nurses were very aware of this, while the doctors, understandably, were more concerned with obtaining early restoration to normal of the patient’s physical signs. As a countermeasure we used small electric fans to blow warm air across the patient while operating the cooling sprays at their finest jets on limited pressure. With luck, plus a combination of concern and trial and error, we achieved something very similar to the regimen advocated by Weiner and Khogali as a result of their controlled research. By the end of my tour of duty in Kuwait these centres had become museum pieces and were rarely used, though whether this was due to better air conditioning, increased awareness of the dangers of heat exposure, or other factors was, to my knowledge, never established. I have now worked in Saudi Arabia for thirteen years and see the yearly pilgrimage (Hajj) referred to by Weiner and Khogali. This short term influx of unacclimatised people of all nationalities poses health problems for the Saudi hosts and I have been most impressed by the concern and courtesy the Saudis show. Each year meetings are held at which problems of the previous Hajj are identified and measures are taken to solve them. It would be a curious turn of fate if I were to find our old Kuwait heatstroke tables, updated, on the roads to Mecca.

Division of Infectious Disease, Children’s Memorial Hospital, Chicago, Illinois 60614, U.S.A.

Medical Department, British Aircraft Corporation, PO Box 1732, Riyadh, Saudi Arabia

77). There

are at least two mechanisms of H. influenza resisampicillin. However, the methods used by Bell and Plowman resulted in a significant overestimation of the incidence of ampicillin resistance in the H. influenzce strains which they studied, and this probably explains their failure to demon-

tance to

strate

RAM YOGEV

doctor

or nurse

ing began.

DOUGLAS

J. MORRISON

CHLORPROPAMIDE/ALCOHOL FLUSHING AND PROSTAGLANDINS HEATSTROKE ON THE

SiR,—When

I

HAJJ

joined the nursing staff of a commercial

com-

pany in Kuwait in 1958 strict routines were laid down for the treatment of heat exhaustion and heatstroke. Heatstroke treatment centres were placed strategically throughout the company’s working and accommodation areas. These units consisted of an air-conditioned room, in the centre of which was a treatment bed, a heavy duty nylon medium mesh net stretched over a frame under which ran a drain. The pillow area of the bed was indented to allow crushed ice to be packed round the patient’s head. At the head and foot there were fine spray-type shower roses, the whole being connected to normal and iced water supplies via a mixing unit. Entrance to these units was by means of a "break the glass" panel containing the door key. Keys to the cupboards inside containing intravenous fluids and medications were held by the medical department with which there was telephone communication. People suspected of suffering from heat effects and with a temperature of 103°F (39-4°C) or over was taken to the nearest heatstroke centre, stripped of outer clothing, put on the bed, and sprayed with cool increasing to cold water. When a 2. Thornsberry C, Kirven LA. Antimicrobial susceptibility of Hœmophilus influenzæ. Antimicrob Agents Chemother 1974; 6: 620-24. 3. Turk DC. A comparison of chloramphenicol and ampicillin as bactericidal agents for Hæmophilus influenzæ type B. J Med Microbiol 1977; 10: 127-31.

SiR,-Dr Strakosch and colleagues (Feb. 23, p. 394) reported that chlorpropamide/alcohol flushing can be blocked by 300 mg aspirin. Since the flushing can also be blocked by naloxone they postulate a brain-mediated prostaglandin/ enkephalin stage in production of the flush. We believe that the flush is much more likely to be mediated by a peripheral mechanism, for the following reasons: (1) alcohol at clinically relevant concentrations powerfully stimulates the production of the vasodilator prostaglandin (PG) E, from human platelets;’ (2) low concentrations of the opiate I-levorphanol enhance PGE, formation from human platelets while &bgr;-endorphin and high concentrations of I-levorphanol inhibit PGE,I formation;2 (3) 300 mg aspirin is a dose which is very unlikely to inhibit either brain or vessel wall PG synthesis while it will inhibit platelet and, probably, lung PG synthesis; (4) facial flushing identical to the alcohol flush can be produced by PGE, infusions.’ 1. Manku MS, Oka M, Horrobin DF. Differential regulation of the formation of prostaglandins and related substances from arachidonic acid and from dihomogammalinolenic acid. ‘I: Effect of ethanol. Prostaglandins Med

1979, 3: 119. 2. Horrobin DF, Manku MS, Oka M, Cunnane SC. selective regulation of formation of 1 and 2 series prostaglandins. In: Future trends in inflammation IV (Royal College of Surgeons, London, February, 1980. Lancaster: MTP Press (in press). 3. Carlson LA, Ekelund LG, Oro L. Circulatory and respiratory effects of different doses of PGE1 in man. Acta Physiol Scand 1969; 75: 161.

936 We suggest that alcohol and activation of one type of opiate receptor can enhance PGEbiosynthesis by human platelets and, possibly, other tissues and that this is the mechanism of the flush. Blockade of platelet PG synthesis will therefore block flushing due to systemic alcohol or opiates. Blockade of opiate receptors will reduce the sensitivity of the system to alcohol even if alcohol does not work via those receptors. Direct application of alcohol or opiates to vessel walls may also cause flushing but high levels of aspirin will be required to block this since vessel PG synthesis is very resistant to aspirin and related drugs. P.O. Box 10, Nuns’ Island,

Montreal, Canada H3E 1J8

DAVID F. HORROBIN MEHAR S. MANKU

The sand bed fluidises intermittently during which time the sinks into the softened sand so that when fluidisation ceases and the bed goes hard the patient is lying comfortably in a depression perfectly moulded to the contours of his body. The bead bed, in contrast, is fluidised continuously and it seems that this continuous gas flow is an important factor in keeping the bed free from bacteria.9 The most obvious mechanism is likely to be desiccation but perhaps static electricity plays a part. Secondly the beads we use, being coated with silicon, are water repellent so the mass of beads remains dry and any excreta remain on the surface sheet from where it is removed by our diligent nurses. In contrast, aqueous mixtures must percolate into a sand bed so that its interior must be a cross between a quicksand and a compost heap. Lastly the beads we use are very small whereas the granules of a sand bed are coarse. The gas flow needed to produce fluidisation depends on the size of the particle-the larger the granule the greater the flow required. Thus when an intermittent flow bed cycles, usually for a few seconds every two minutes, a powerful blast of air is forced through the sand and it is not surprising that the bacterial count rises. Our observations on the bacteriological safety of bead beds apply only to those beds in which siliconed glass microspheres are used in beds designed for continuous fluidisation. They certainly do not apply to intermittent flow sand beds.

patient’s body

’

THE MALARIAL HYPNOZOITE

SIR,-Following adoption of the recently introduced term "hypnozoite" for a relatively unknown but potentially very important stage of Plasmodium, 1,2 I have been asked by several clinicians to clarify the origin of the word in a journal readily available to them. Organisms shown in 1976 to be latent sporozoites3-5 were seen in the life cycles of three species of mammalian Isospora which, like Plasmodium, is a coccidian protozoon. On the basis of these observations, I suggested that Plasmodium may have the ability to survive in tissues in the same way.3 The descriptive term "hypnozoite" was created for this (at the time hypothetical) stage of Plasmodium.3.6.7 It is derived from the Greek hypnos (sleep) and zoon (animal), and was chosen to 6 convey the concept of dormancy. The important discovery of presumed hypnozoites of Plasmodium has now been reported.2 Hypnozoites might be responsible for extended prepatent periods and perhaps for the phenomenon of "true" relapse in malaria. I acknowledge support from the South African Medical Research Council and the S.A. Council for Scientific and Industrial Research.

Department of Zoology, University of the Witwatersrand, Johannesburg, 2001 South Africa

MILES B. MARKUS

BACTERIOLOGICAL HAZARDS OF FLUIDISED BEDS

SIR,-Dr Morris (March 29, p. 721) points out that bacteria are shed when a patient is turned on a fluidised sand bed if that bed is fluidised at the moment of turning, and he wonders if the same thing may happen on the fluidised bead bed. The short answer, from our observations using slit samplers, is that it does not. There are sufficient differences between the bead bed described in our paper (March 15, p. 568) and the sand bed whose bacteriological properties are described by Williams and Mansell8 to account for the apparent disagreement between us. The two machines differ in three respects.

AY. Modern malariology progress. Parazitologiya 1979; 13: 461-73. 2. Krotoski WA, Krotoski DM, Garnham PCC, Bray RS, Killick-Kendrick R, Draper CC, Targett GAT, Guy MW. Relapses in primate malaria: discovery of two populations of exoerythrocytic stages. Br Med J 1980; i: 153-54. 3. Markus MB. Possible support for the sporozoite hypothesis of relapse and latency in malaria. Trans Roy Soc Trop Med Hyg 1976; 70: 536. 4. Mehlhorn H, Markus MB. Electron microscopy of stages of Isospora felis of the cat in the mesenteric lymph node of the mouse. Z Parasitenk 1976;

Newcastle General Hospital, Newcastle upon Tyne NE4 6BE

C. W. THOMSON

NIACIN FOR NICOTINE?

SiR-Although smoking has its social and psychological aspects most people smoke to maintain a certain nicotine level in the bloodstream.’ In many becomes addictive.2

cases

this need for nicotine

Morphine works by tricking the endorphin receptorsmight not nicotine similarly dupe the niacin (vitamin BJ) receptors of the CNS? Niacin is chemically very similar to nicotine ; indeed the early name for niacin was nicotinic acid. Is it not possible, then, that nicotine fills niacin receptor sites and creates a deficiency of a nutrient required by the CNS? Perhaps this is why some say they need a cigarette to "calm their nerves". If this hypothesis is valid, it might be possible to wean some smokers off their nicotine addiction by administering nicotinic acid (niacin). Canadian Journal of Health and Nutrition, 73 Albany Avenue, Toronto, M5R 3C2 Canada

REBECCA CLARKES

1. Lysenko

51: 15-24. 5. Markus MB.

UNCLASSIFIED MENTAL RETARDATION

SIR,-Dr Ounsted and her colleagues (March 29, p. 705) still seem to think that your editorial on Unclassified Mental Retardation last year was mainly about a paper of theirs which linked treatment with methyldopa between 16 and 20 weeks of gestation with a barely noticeable reduction in neonatal head circumference. I still think your editorial was mainly about our

Isospora of mammals in the intermediate host.

Proc 5th Int 395. 6. Markus MB. Terminology for invasive stages of protozoa of the subphylum Apicomplexa (Sporozoa). S Afr J Sci 1978; 74: 105-06. 7. Markus MB. Sarcocystis and sarcocystosis in domestic animals and man. Adv Vet Sci Comp Med 1978; 22: 159-93. 8. Williams CSH, Mansell R. Fluidized sand beds. Nursing Times March 22,

Congr Protozool (New York) 1977:

1979, p. 489.

9.

Sharbaugh RJ, Hargest TS. In: Air fluidised bed: Clinical and research symposium, at Medical University of South Carolina. 1971: 76. 1. Russell MAH, Jarvis MJ, Feyerabend C. A new age for snuff. Lancet, 1980,

i: 474-75. 2. Kozlowski LT. The role of nicotine in the maintained

Merchandising 1980; 1: 36-43.

use

of cigarettes, Drug