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Red blood cells under zero gravity.

Photographs taken automatically, by slit-capillary photoviscometer (slit gap12 - 5 pm), on space shuttle Discovery on Jan 24, 1985.Upper: after 40 s of stasis.Lower: same sample after 6 min, showing aggregates formed of rouleaux

arranged in parallel or partly crossed pattern but no sludging or agglutination.Sample of blood from patient with coronary heart disease and history of

carcinoma of colon.

Blood samples, from healthy donors and from patients withhistories of ischaemic heart disease, cancer of the colon, insulin-dependent diabetes, and hypertension, were adjusted to 30%haematocrit and studied electronically and photographicallyduring flow and during stasis in the slit-capillaryphotoviscometer.2,3 The red cells remained normal under zerogravity; there was no evidence of crenation, burr cells, or unusualshape changes. Aggregation proceeded normally, resulting inrouleaux and aggregates formed from rouleaux. In other words,aggregation was as expected in normal blood, yet most of the bloodused was from donors in whom sludging does take place and whohave evidence of abnormal clumping of red cells.3,4 Zero gravitymight thus have a beneficial effect on red cell aggregationmorphology. There is no sedimentation of red cells under zero

gravity or at least very little in comparison with sedimentation onearth, so experiments in which red cell sedimentation presents aproblem might be done more easily and more cleanly underconditions of near-zero gravity.During this mission we obtained in our vibration-proof

microscope perhaps the very first perfect photomicrographs of redcells and aggregates under zero gravity (see figure).These preliminary results suggest that the changes in the shape of

red cells in astronauts reported by the Johnson Space Centers arenot due directly to zero gravity, but are secondary to changes in,presumably, calcium metabolism. If red blood cells tend to behavemore normally under near-zero gravity in vitro, this might be ofsome value for the in vitro preservation of stored blood.Furthermore-if any parallel with in vivo conditions is

permissible-the red cells in astronauts, notwithstanding their

bizarre shapes, might remain relatively fluid and deformable. Weresuch shapes to occur on the ground serious microcirculatorydisorders would ensue.

We hope to pursue these researches on another orbital flight later this year.The team at Cape Canaveral included Mr Peter Osman, Mr Brian Maguire,Mr Henry Jedrzeczyk, and Mrs Barbara Brotherson-Jedrzejczyk, for whosesupport I am greatly indebted. Financial support included grants from theDepartment of Science and Technology, CSIRO, and Bushell Trust, anddonations from Esso, Hawker de Havilland, Qantas, Jones Lang Woottons,and USRA (American Universities Space Research Association).

Department of Medicine,University of Sydney,Sydney 2006, Australia L. DINTENFASS

1. Dintenfass L Background and development of the space project on "aggregation of redcells". Australas Phys Eng Sci Med 1983; 6: 156-65.

2. Dintenfass L, Osman P, Maguire B. Measurement of aggregation of red cells in space: aproject for the NASA space shuttle. J Electr Electron Eng (Australia) 1984; 4:118-25.

3 Dintenfass L, Jedrzejczyk H, Willard A. Photographic, stereological and statisticalmethods in evaluation of aggregation of red cells in disease I: Kinetics of

aggregation. Biorheology 1982; 19: 567-77.4. Dintenfass L, Liao F-1, Francis D, Willard A. Quantitative study of morphology of

aggregation of red cells in patients blood and in the reconstituted suspensions. ClinHemorheol 1984; 4: 223-36.

5 Kimzey SL. Hematology and immunology studies. In: Johnston RS, Dietlein LF, eds.Biomedical results from Skylab. Washington, DC: NASA, 1977: 249-82.

6. Goode A. Microgravity research: a new dimension in medical science. Lancet 1981, i:767-69.

7. Dintenfass L, Julian DG, Seaman GVF. Heart perfusion, energetics and ischemiaNew York: Plenum, 1983.

8. Dintenfass L Hyperviscosity in hypertension. Sydney: Pergamon Press, 19819. Lake B, Dintenfass L. Blood viscosity in the "ischaemic" exercise ECG. Lancet 1975;

ii: 1092.

ORAL CONTRACEPTIVE USE AND BREAST CANCERIN YOUNG WOMEN IN SWEDEN

SIR,-Two investigations have suggested a relation between oralcontraceptive use (OC) and breast cancer in young women.I,2 Thesestudies were done in areas where OC use was established early andhad become extensive. We report here the findings in a study inanother such area, southern Sweden.A case-control study was done on 80 consecutive cases of breast

cancer in women born in 1939 or later and diagnosed at the age of 45or earlier. This number constitutes 40% of all cases in the healthcare region of southern Sweden in 1979-83, Malmö being excludedbecause of screening activities for breast cancer. The cases wereinterviewed personally by their physician. Three healthy women,selected from the population registry, were individually matched toeach case on birth year and parish. 225 controls remained afterlosses because some controls declined the interview and otherscould not be contacted. The controls were spoken to over thetelephone by a female questioner.When the data were analysed by conditional logistic regression3 3

women who had started OC use at 20-24 years of age had threetimes the risk of developing breast cancer before 46 years of agecompared with non-users (table). ’

The relative risk increased with earlier age ofOC start. Because an

early age ofOC use was highly correlated with the duration of use, aunique effect of duration could not be found when starting age wasaccounted for. Women who had started OC use after their first

RELATIVE RISK OF BREAST CANCER AND OC USE IN RELATION TO

STARTING AGE AND NUMBER OF CASES AND CONTROLS WITH

DISSOLVED MATCHINGI

*Ad]usted for age at menarche and age at first full-term pregnancyj-95% confidence interval

749

pregnancy had a lower relative risk than others, although thedifference was not significant.The risk estimates were adjusted for age at menarche and age at

first full-term pregnancy. In our investigation both a low age atmenarche and a high age at first full-term pregnancy were related toincreased breast cancer risk (p=0-12 and p = 0 - 06, respectively).Different brands of OC were not analysed.To investigate the validity of using two interviewing techniques

17 healthy OC users personally interviewed about their OC use bytheir physician in 1980 in connection with health check-ups wereinterviewed again in 1984 by telephone. The reported starting agewas, on average, 1’ 8 years lower when the interview was bytelephone. This quick validity check indicates that any bias due todifferent interviewing techniques would affect the study in thedirection of underestimation.Our results accord with those of Harris et al,4 Paffenberger et al,6

Pike et alu5 and McPherson et al2 but differ from those of theCenters for Disease Control Cancer and Steroid Hormone Study.7Another study, by Rosenberg et al,8 though reported negative,shows a significant association between early OC use and breastcancer risk in the same age groups.Our results, taken together with earlier reports linking early OC

use with breast cancer, are a matter of great concern in respect ofOCuse by young women. A full report of our study will appearelsewhere.

Department of Oncology,University Hospital,S-221 85 Lund, Sweden H. OLSSON

Department of Internal Medicine,Malmo General Hospital M. LANDIN OLSSON

Southern Swedish

Regional Tumour Registry,University Hospital, Lund

T. R. MÖLLER

J. RANSTAMP. HOLM

1 Pike MC, Henderson BE, Krailo MD et al. Breast cancer in young women and use oforal contraceptives: Possible modifying effect of formulation and age at use. Lancet1983, ii 926-930

2 McPherson K, Neil A, Vessey MP et al. Oral contraceptives and breast cancer Lancet1983, ii: 1414-15

3 Storer B, Wachholder S, Breslow NE. Maximum likelihood fitting of general riskmodels to stratified data. J Roy Stat Soc C 1983; 32: 172-81

4 Harris N, Weiss N, Francis A et al. Breast cancer in relation to patterns of oralcontraceptive use Am J Epidemiol 1982, 118: 643-51.

5 Pike MC, Henderson BE, Casagrande JT et al. Oral contraceptive use and earlyabortion as risk factors for breast cancer in young women Br J Cancer 1981; 43:72-77.

6 Paffenberger RS, Kampert JB, Chang H-G. Cancer risk as related to the use of oralcontraceptives during fertile years. Cancer 1977; 39: 1887-91.

7 The Centers for Disease Control Cancer and Steroid Hormone Study. Longterm oralcontraceptive use and the risk of breast cancer. JAMA 1983; 249: 1591-95.

8 Rosenberg L, Miller DR, Kaufman DW et al Breast cancer and oral contraceptive use.Am J Epidemiol 1984, 119: 167-76

MOBILE INTENSIVE CORONARY CARE

SIR,-Dr Mathewson and his colleagues’ paper (Feb 23, p 441)focuses attention once more on the efficacy of mobile intensivecoronary care units (MICCUs). Mathewson et al showed that, overa 15-month period, an area possessing an MICCU (Ballymena) hada community mortality rate of 50% for acute myocardial infarction(AMI) whereas an area without an MICCU (Omagh) had a

community mortality rate of 63%. The figures for patients aged lessthan 65 years were 34% and 55%, respectively. Treatment in thetwo areas differed only in that it was provided about two hoursearlier in the area served by the MICCU.Mathewson et al suggest that the impact of early pre-hospital

coronary care on community mortality has been "seriouslyunderestimated". I have no argument with that statement, but theygo on to say that treatment of AMI is most effectively delivered bymeans of an MICCU-there I have to disagree.In Levenstein’s study’ 129 general practitioners collaborated

over a 14-month period. The objectives were to reach all patientswith symptoms of AMI as promptly as possible, and to institutetherapy according to a simple protocol where the emphasis was onprophylactic antiarrhythmic drugs. Besides opioids, atropine 0 - 6mg was routinely given to all patients with a pulse rate below

60/min, and those with pulse rates above 60/min were givenlignocaine 100 mg intravenously and 200 mg intramuscularly. Ifectopic beats were noted after atropine-induced tachycardia-lignocaine was given. The frequency of death from arrhythmia waslow at 1-8% (6 out of 333 patients with confirmed AMI who werealive when the GP arrived); the arrhythmia in these 6 patients wasprobably ventricular fibrillation (VF), and detailed study showedthat 5 of them had received inadequate or no antiarrhythmic treat-ment. The overall community death rate in the 445 patients of theparticipating GPs was 28-3%; it was 23-3% in the 356 patientsbelow the age of 70. The patients were transferred to hospital byordinary ambulance and defibrillators were not available in the pre-hospital phase. Levenstein concluded that, in the pre-hospital phaseof AMI, GPs were able to administer a service which comparedfavourably with MICCUs at no extra cost to the community andwith very little extra strain on the GPs themselves.My paper on the Woolpit coronary care scheme2 represents my

experience in treating AMI as a GP in a five-partner rural EastAnglian practice with a list size of about 11 000. The study tookplace over a 56-month period ending in October, 1984. The protocolwas almost identical to that in Levenstein’s study, and the primaryaim was to reach all suspected AMI victims as quickly as possibleafter the onset of symptoms. Opioids were administered wherenecessary but no patients were given prophylactic antiarrhythmicagents in the pre-hospital phase. Instead each patient was

continuously monitored by cardioscope with a defibrillator on handto deal with life-threatening arrhythmias. There were 13 confirmedcases of AMI. 5 patients required defibrillation in the pre-hospitalphase, of whom 2 are long-term survivors. The communitymortality was 31% (4 deaths).

Levenstein’s study concentrated on arrhythmia prophylaxiswhereas the Woolpit scheme relied on reversal of VF by DC shock.However, community mortality for the two GP schemes wasessentially the same and far better than that in Ballymena, where anMICCU operated, or in Omagh.Any scheme designed to reduce the case fatality rate in AMI must

contend with the fact that, without treatment, of those who aredestined to die following AMI, 25% will have done so within 15min, 40% will be dead within the first hour, and 80% will have diedwithin four hours. In Levenstein’s study, 38% of suspected AMIvictims had been seen within an hour and 75% within four hours.The figures for the Woolpit scheme were 38% and 69%,respectively. Mathewson et al illustrate only the cumulativeadmission-rate related to time of onset of symptoms, but it wouldseem that the patients in both GP-based studies were seen at anearlier stage.The secret of success therefore is not how the treatment is

delivered, but the speed with which it was provided. Furthermore,the treatment given by the Ballymena MICCU (with the possibleexception of defibrillation) is within the competence of the GP-namely, the administration of analgesics, antiarrhythmic drugs, andanti-failure agents.In general, it is the GP who can be first on the scene, and in the

pre-hospital treatment of AMI the most effective delivery system islikely to be the GP who responds rapidly and administersprophylactic antiarrhythmic treatment. It is the GP’s role in thetreatment of AMI that has been seriously underestimated.

Health Centre,Woolpit, Bury St Edmunds,Suffolk IP30 9QU ANDREW M. MASON

1. Levenstein JH Emergency management of acute myocardial infarction by the generalpractitioner S. Afr Med J 1976; 50: 531-38

2. Mason AM, Pre-hospital coronary care: an evaluation of various schemes. Care Crit Ill(in press)

THROMBOSIS IN MYOCARDIAL INFARCTION

SIR,-Your Feb 16 editorial states that "there is now strongevidence that myocardial infarction is caused by coronary arterialthrombosis" and, later, that "little is known about the mechanism ofobstruction at the very onset of infarction". The two statements are

contradictory. Coronary angiography during the acute stage of