Vol.2

No.1

ISSN 1349-5232

October, 2005

Journal of Medical Safety(Print version)

CONTENT
Health Effects due to Air Pollution in China
Stefan Hirschberg and Thomas Heck (Paul Scherrer Institut CH-5232 Villigen PSI, Switzerland)

Study on the Effects of Water Treated with Different Doses of Untraviolet Lighton Cultural Properties of Bifidobacteria, Lactobacilli and Bakery
V.K. Ilyin, S.S. Yesiev*, L.V. Rakitskaya, D.A. Tyurina, Z.O. Solovyova, I.G.Ogorodnikov* E.A. Deshevaya, and V.H.
Agnaev (Russian Federation State Scientific Research Center Institute of Biomedical Problems, Russian Academyof Sciences (RAS IMBP RF SSRC) (Moscow), *Consulting company “Ogorodnikov and Partners”, Russia)

Mind/Body Medicine and Stress Management
Mutsuhiro Nakao (Teikyo University School of Medicine, Tokyo, Japan)

The Possibility to Communicate, Interchange and Share the Health and Risk
Related View Among Ordinary People Living in Different Asian Countries
Moriyama, M.*, Tanaka, K., Ushijima, K., Miyake, Y. and Arakawa, M. (Dept. of Public Health, Fukuoka University
School of Medicine, Fukuoka, Japan)

Ecocytogenetics: A New Approach to Preventive Medicine in the 21st. Century
A. Fucic1 PhD, J.N. Lucas2,3 PhD (1Institute for Medical Research and Occupational Health, Zagreb, Croatia;
2Lawrence Livermore National Laboratory, University of California, California, USA; 3American Laboratory
Technologies, Inc., Arlington, Virginia, USA)

Death May Have Its Benefits – The Role of Forensic Pathology in Medical Audit
Gilbert Lau (Centre for Forensic Medicine, Health Sciences Authority, Republic of Singapore)

Health Promotion, Health Education and Risk Management: Asian Perspectives
Majumder M. A. A. (Department of Medical Education, Universiti Sains Malaysia, Malaysia)

JMS

Journal of Medical Safety

Published by URMPM, Copyright C) by URMPM
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Chiho Watanabe, JapanJMS Editorial Office Shirley V. V. Chaves (URMPM International Secretary)
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Journal of Medical Safety Vol.2 No.1, 2005, October

Health Effects due to Air Pollution in China
Stefan Hirschberg and Thomas Heck
Paul Scherrer Institut CH-5232 Villigen PSI, Switzerland

Abstract
This paper summarizes the assessment of health effects carried out by Paul Scherrer Institute (PSI) within
the China Energy Technology Program (CETP). CETP has been sponsored and coordinated by ABB in
conjunction with the Alliance for Global Sustainability (AGS). PSI, together with American (MIT), numerous
Chinese, Japanese (Tokyo University) and Swiss (ETHZ and EPFL) partners investigated how the future
electricity supply in China could be made more sustainable.
The impacts of outdoor air pollution on health and environment were assessed. The main emphasis has
been on the rapidly expanding electricity sector. Most detailed results were obtained for the highly
industrialized and energy intensive Shandong Province but a wide spectrum of findings considers the whole
China. In accordance with the general objective of CETP “true” costs of electricity generation were
estimated, reflecting not only the (internal) production costs but also damages to health and environment.
This was done both for the current technologies as well as for candidate technologies that could be
implemented within the time horizon of 20 years.
According to the present study air pollution in China currently causes about nine million Years of Life Lost
(YOLL) per year. In relative terms sulfates dominate the health impacts and SO2 is thus indirectly the major
contributor, followed by nitrates and primary particulates. The number of YOLL per ton of SO2 emitted in
China is on average almost seven times higher than the average for EU; for Shandong the corresponding
factor is about 11. The total (internal plus external) costs of environmentally-friendly electricity supply
strategies are significantly lower than those of the seemingly cheaper, but “dirty” and non-sustainable,
strategies based on traditional coal technologies. Cost-efficient reduction of health and environmental
damage, and of the corresponding external costs, can be achieved by implementation of “clean-coal”
technologies, together with fuel diversification, including extended use of natural gas and nuclear energy.
Keywords: Health Risks, Energy Chains, Valuation, Comparative Assessment, External Costs.

increasingly aware about the physical and economic
consequences to the public health sector and theenvironment, whose extent depends on theirdecisions. In practical terms, sustainable energy
development means that human health andenvironmental impacts, resource depletion andintergenerational equity implications should beconsidered along with traditional economic and

1. Introduction
Along with enormous benefits all forms of energy
supply have some negative impacts on people and on
the environment. In particular, the release ofpollutants to air, water and soil can have a profound
impact to human health, agricultural crops, naturaland man-made environments via different pathwaysof exposure. Decision-makers around the world are-1-

Journal of Medical Safety Vol.2 No.1, 2005, Octobertechnical issues in the planning and use of energy
options.
Many studies have been undertaken in recent years
on the health and environmental impacts associatedwith energy supply. Of particular importance in thiscontext is the ExternE Project of the European Union(European Commission, 1999). A generally acceptedframework for comparative assessment of suchimpacts has been developed and implemented for anumber of countries. Recent enhancements andextensions include PSI’s work on future systems
under Swiss conditions (Hirschberg et al., 2000) andstudy of impacts in China within the China Energy
Technology Program (Hirschberg et al., 2003b). The
studies identify, quantify and, to the extent possible,
determine the economic value of health andenvironmental impacts.

B

B

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2.1 Air pollutants and their health impacts

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The following major emissions are addressed in thehealth effect comparisons covered here:• Particulates. Ambient air pollution particulates
are a complex mixture, varying in size and incomposition. Many epidemiological studies foundevidence of adverse acute health effects of particulate
air pollution. There is also strong epidemiologicalevidence of chronic health effects. Because
particulate air pollution is a complex mixture rather
than a single substance, there is a lot of diversity in
how particulate air pollution is characterized invarious epidemiological studies. Internationally, there
are many studies showing acute health effects of(inhalable
particulates
expressedas
PM 10
particulates), or total suspended particulates (TSP). In
Europe, a number of studies refer to black smoke(BS). Some studies, mostly from North America, show
the effect of finer fractions such as PM 2.5 or sulfates.
There is some evidence, that these fine fractions areassociated with greater risks than PM 10 . It may also
be that the toxicity of particulates is greater according
to their acidity, and less according to their solubility.
For modelling, we distinguish between “primaryparticulates” which are emitted directly from theemission sources and the “secondary particulates”, i.e.
sulfates and nitrates, which are formed in theB

B

B

2. Health Effects of Normal Operation

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The emphasis in the assessment is on air pollutants,
whose effects are dominant. Health impacts due toemissions to water have not been analyzed in detail
but they are of secondary importance, particularly
when energy systems in Western Europe areconsidered. Furthermore, the assessment concerns
impacts on public; occupational damages arenormally much less significant and are considered to
be by and large internalized, at least in OECD.

B

atmosphere from SO 2 and NO x emissions.
Secondary particulates are assumed to cause similar
health impacts as primary particulates.
• Sulfur dioxide (SO 2 ). SO 2 is held responsible
for a variety of environmental damages, particularly
on human health, ecosystems, crops and building
materials. As a precursor of sulfates (secondary
particulates), sulfur dioxide is indirectly a major
contributor to long-term (“chronic”) mortality andseveral morbidity effects. Also evidence of the acutehealth effects associated with SO 2 is available. SO 2
can cause direct economic damages by reducing crop
yields. Acidification resulting from SO 2 emissions is
also hazardous to natural ecosystems.
• Nitrogen oxides (NO x ). Currently, the direct
effects of NO x emissions are not being assessedthough positive associations between NO x and daily
mortality or respiratory hospital admissions in several
European cities have been reported. NO x is aprecursor to nitrates (secondary particulates). Theview is supported that the apparent NO x effects may
be due to particulates, or at least, are highly
dependent on background particulate levels.
• Ammonia (NH 3 ). Ammonia emissions play animportant role in the chemical transformation of sulfur
and nitrogen oxides into hazardous secondary
particulates (ammonia sulfates and ammonia nitrates).
• Radiation. Impacts on human health andecosystems can occur when radioactive substances
are set free into the environment. During normal
operation of nuclear power plants and other facilities
in the nuclear fuel cycle, the emissions of radioactivity
are at low levels. In relative terms stages in the
nuclear fuel cycle such as mining/milling or
reprocessing emit more radioactivity than the power
plant. The impacts of these emissions are reflected in
the comparisons. Health effects related tohypothetical severe nuclear accidents, which mightlead to large releases of radioactivity, need to beaddressed separately.
B

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B

2.2 Health impact assessment methodology
The impact pathway approach allows the impact fromemission sources within specific energy chains to be
estimated. The main features of the approach are as
follows:(a) In the full scope analysis, all relevant stages inthe various energy chains are covered (extraction,
fuel processing, transport, power generation, waste
management and storage).
(b) The analysis steps involve technology and sitecharacterization, prioritization of impacts to theenvironment, quantification of burdens (e.g.
emissions), description of the receiving environment,
quantification of environmental damage (using,whenever applicable, dispersion models forJournal of Medical Safety Vol.2 No.1, 2005, Octoberatmospheric pollutants and dose-response functions),
and, if of interest, economic valuation. Figure 1
shows the analysis steps.

calculated by implementing the receptor distributions
and the marginal increases of pollutants into thedose-effect models. Finally, to obtain the damage
costs, the impact end-effects are multiplied by themonetary unit cost per incident.
For the basic health effect functions, a linear relation
between marginal changes of concentrations andhealth impacts is assumed. The World HealthOrganization (WHO, 1999) adopted a ‘no threshold’
position for particulates and ozone. ExternE(European Commission, 1999) recommended toquantify health effects from particulates, SO 2 , andozone on a ‘no-threshold’ basis.
Acute mortality effects are associated withcorrelations between short-term (order of days)
changes in concentrations of air pollutants and shortterm changes in mortality. Chronic mortality refers tolong-term (order of years) effects of air pollution. The
measure used to quantify mortality effects is the
reduction of life expectancy expressed as “Years ofLife Lost” (YOLL). The individual YOLL are summed
up to total YOLL for the whole affected population.
Mortality studies usually measure changes inmortality rates of the population. Non-trivial extra
steps are needed to convert mortality rates into YOLL.
The slopes of the exposure-response functions used
for impact assessment of mortality and morbidity aresummarized in Table 1. (The table and the following
results refer to the state-of-the-art as of years
2003/2004; research on impact and valuation factors
is still ongoing e.g. in European ExternE follow-up
projects.) Among the reference sources provided in
the table we emphasize the study by Pope et al.,1995), carried out on behalf of American Cancer
Society (ACS). More than 500’000 adult individuals in
151 US cities were followed over a period of about 8
years (1982-1989). A clear correlation was foundbetween mortality and air pollution after adjusting forage, sex, race, current cigarette smokers, former
cigarette smokers, pipe/cigar smokers, exposure topassive smoking, occupational exposure, education,body-mass index (BMI), and alcohol use. The
adjusted mortality rate was about 17% higher for adifference of 24.5 µg/m 3 PM 2.5 between the highest
and lowest polluted areas. For sulfates, an increaseof mortality of about 15% was associated with anincrease of 19.9 µg/m 3 SO 4 . The strongest
associations were observed for cardiopulmonary
disease and lung cancer, with insignificant
associations with death due to other causes. Resultsfrom the ACS study were used in ExternE to derive adose-effect model. The results for a 16-years followup period (1982-1998) confirm ed again the clear
correlation between ambient fine particulate
concentrations and mortality (Pope et al,. 2002) .

Fig. 1
Impact pathway approach.
Emissionsto Air and Water

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Dispersion / Deposition
Increase of regional
pollutant Concentrations

Impacts
Human beings, Animals & Flora,
Buildings

Damage Costs
health, crops, cultural assets

The basic tool used for estimation of health andenvironmental impacts, based on the “impact pathway
approach”, is the integrated impact assessment
model EcoSense, developed by Stuttgart University(European Commission, 1999; Krewitt et al., 2001).
The model, earlier developed and used for external
cost assessment in Western Europe, was modified for
applications to South American conditions (Krewitt etal., 2001), and later to Chinese/Asian (Hirschberg etal., 2003b) and Russian (Droste-Franke et al., 2002)
conditions.
This involves the development andimplementation of application-specific “Reference
Environment Databases”, covering receptor data,
meteorological data and emission data.
EcoSense allows calculations of fuel cycle
externalities to be carried out and supports theassessment of damage resulting from the operation ofa single point source (e.g. a power plant) at a given
location, taking into account pre-defined backgroundconditions. Furthermore, the effects of changes inemissions from specific sectors (e.g. energy, industry,transport, households, etc.) can be assessed on acontinental, national, provincial or community level.
In a first step, the emission inventories are organizedaccording to administrative units and sectors. The
Windrose Trajectory Model (WTM) employed by
EcoSense simulates the long-range atmospherictransport and chemical conversion of air pollutants,
resulting in concentrations and deposition fields. The
physical impact on health and environment are
T

T

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T

T

-3-

Journal of Medical Safety Vol.2 No.1, 2005, Octobercountries (European Commission, 1999) are,respectively, 3.1 million and 110’000 US$ 2000
(undiscounted). Adjustments for other countries are
based on the assumption that there is an “elasticity”
of WTP with respect to real income.

Table 1
Exposure-response functions for the quantification ofhuman health impacts according to (European
Commission, 1999) with updates from (Friedrich andBickel, 2001). The exposure response slope, f er , hasunits of [cases/(yr-person-µg/m 3 )] for morbidity, and[YOLL/(yr-person-µg/m 3 )] for mortality.
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3. Selected assessment results

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As an example of assessment results Fig. 2 shows
the distribution of mortality due to air-pollutant
emissions from China’s power sector. There is a large
variation of these effects, with the highest damage
occurring in areas with intensive industrial activities
and high density of population.

Fig. 2Distribution of mortality due to current emissions of air
pollutants from China’s power sector (Hirschberg etal., 2003b).

Generally, damages resulting from the emission of aunit of pollutant are high if the number of affected
receptors is very large. Table 2 shows factors for the
impact “mortality” in terms of Years of Life Lost fordifferent countries and different locations withincountries. It can be seen clearly that the specific
YOLL factors depend strongly on the location of theemission source.

To obtain the damage costs, one multiplies thenumber of impacts (for example, the number ofasthma attacks) by the cost per case (US$ per
asthma attack). For health impacts, the unit costs
include the cost of illness, wage and productivity
losses, which are market based factors, as well as
non-market costs that take into account an
individual's willingness-to-pay (WTP) to avoid the riskof pain and suffering. For mortality impacts, one
needs to determine the Value of a Life Year Lost(VLYL) or, equivalently, the Value of a Life Year
(VOLY), which in turn is based on the so called Valueof Statistical Life (VSL), the amount of money that anindividual is willing to pay to avoid premature death.
The median values for VSL and VLYL (for valuing
long-term mortality impacts) in most industrialized-4-

Journal of Medical Safety Vol.2 No.1, 2005, OctoberTable 2

Fig. 3Comparison of different countries and locations –Mortality risk in terms of “Years of Life Lost” (YOLL)
resulting from the emission of one kilo-tonne ofpollutant (Reference years 1990/1998).

Damage costs due to outdoor air pollution for thereference year 1998 in Shandong Province and in thewhole of China (Hirschberg et al., 2003b).
Power Sector
Shandong

Crops

8

Morbidity

Mortality

25

Shandong

Power Sector
China

45

196

China

0

50

100

150

200

250

Billion US $ per Year

Figure 4 shows the relative contributions of different
health impacts to the total morbidity costs. Morbidity
costs are dominated by chronic bronchitis andrestricted activity days. The figure refers to air
pollution from Shandong's power sector, but therelative distribution of morbidity costs is similar for theother air pollution sources considered.

Fig. 4
For the calculation of external damage costs, thevarious impacts have to be valuated in monetary
terms. The contributions from the different impacts
resulting from the emissions of various hazardous
pollutants are summed up over all affected receptors.
All results provided in the following figures include thecontributions from the rest of energy chainsassociated with the considered power planttechnologies.
Figure 3 summarizes the current external damage
costs due to air pollution from the power sector andfrom all sectors in Shandong province and in thewhole of China. The total external costs are
dominated by mortality, followed by morbidity impacts.
Compared to the large mortality and morbidity costs,
crop losses contribute only marginally to the total
damage costs.

-5-

Distribution of external damage costs of morbidity due
to air emissions from Shandong power sector(Hirschberg et al., 2003b).
Respiratory hosp.
admission
0.2%
Congestive heart
Chronic coughfailure2%
0.1%

Cerebrovascularhosp. adm.
1%
Lower resp.
symptoms
0.2%
Cough
3%
Bronchodilator
usage
3%

Restricted activity
days
38%

Chronic bronchitis
53%

Figure 5 shows the “true” costs of electricity
generation in Shandong, a relatively highly
industrialized province of China. It should be notedthat currently only conventional (reference) coal
power plants without Flue Gas Desulfurisation (FGD)
are operating in Shandong. The costs are provided
for a variety of coal technologies in few selected
locations in Shandong, for (possible) natural gas plant

Journal of Medical Safety Vol.2 No.1, 2005, Octoberin Jinan and for (possible) nuclear power located on
the coast of Shandong. Jinan is the largest city in
Shandong, and is located inland. Qingdao is locatedon the coast. Heze and Weihai are located in thesouth-western part of the province and in the northernpart of the Shandong peninsula, respectively. For
comparison, the average external costs for
Shandong’s power sector are shown.

Fig. 6
Cost-benefit analysis of "clean" versus "dirty"
strategies of power supply in Shandong Province inyear 2020, including LCA contributions. CO2 damage
costs are not considered though their inclusion would
further strengthen the benefits of cleaner strategies(Hirschberg et al., 2003b).
Cost:

Benefit (avoided external damages):

Additional internal costs
compared to coal without FGD

US Cents per kWh

15.00

18.4
15.2

14.5

Clean Coal
Technology +Diversification

Radiation
CO2-equivalentParticulates
NOx
SO2
Internal Costs

25.00

20.00

Coal, FGD

Fig. 5“True” costs of electricity generation by various
means in China, Shandong Province; contributions toexternal costs from major pollutants and global
warming(CO2-equivalent)
are
shown
(Hirschberg et al., 2003b).

Cost

Morbidity

Mortality

0.5

Benefit

10.2

0.9

Cost

15.4

Benefit
0

10.7

Crops

compared to coal without FGD

10.3

2

4

6
8
10
12
Billion US $ in Year 2020

14

16

18

10.00
7.7

7.7
6.5

5.8

6.1

5.00

6.9

6.4

5.4

Uncertainty analysis of complex integrated models
such as those used in the impact pathway approachis a highly demanding task. Not all underlying issues
are fully resolved within the current state-of-the-art.
An approximate quantitative estimate of uncertainties
has been implemented.
The impact pathway analysis is essentiallymultiplicative. According to the central limit theorem ofstatistics, the “natural” distribution for multiplicative
processes is a lognormal function. For the uncertainty
analysis of the impact assessment, two basic
measures are important: geometric mean value (orgeometric expected value) µ g and geometric standard
deviation σ g . For a lognormal distribution,
multiplicative confidence intervals around thegeometric mean can be derived easily from thegeometric standard deviation. The 68% confidence
interval is approximately [µ g /σ g , µ g *σ g ], and the 95%
confidence interval is approximately [µ g /(σ g ) 2 ,µ g *(σ g ) 2 ]. Table 3 summarizes the uncertainties
related to the dominant end-point “chronic mortality”.

4.3

3.3

Jinan Gas CC

Jinan Coal IGCC

Jinan Coal AFBC

Jinan Coal Dry FGD

Jinan Coal Wet FGD

Jinan New Coal, low
S

Nuclear ALWR

Jinan Coal Ref.

Qingdao Wet FGD

Qingdao Dry FGD

Qingdao Sea Water
FGD

Heze Coal Ref

Qingdao Coal Ref

Weihai Coal Ref

Shandong average

0.00

Over 18'000 electricity supply scenarios for the years
2000 to 2024 were analyzed for Shandong Province
within CETP. External costs were estimated for morethan 100 selected scenarios. Figure 6 shows resultsfrom a cost-benefit analysis for two selected electricity
supply strategies for Shandong Province in the year
2020 in relation to a strategy based on the use of coal
without scrubbers (FGD). The two cleaner scenarios
shown are: (1) conventional coal with FGD; and (2)improvements of existing generation—retirement ofaging units, retrofits (including FGD), coal treatment—
together with clean/advanced coal technologies,
nuclear and some natural gas. Since the relative
difference in internal costs is quite small, the total(internal plus external) costs of much moreenvironmentally friendly strategies are clearly lower
than the full costs of seemingly cheap, “dirty”, nonsustainable strategies.

B

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B

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B

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B

B

-6-

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P

Journal of Medical Safety Vol.2 No.1, 2005, Octobersites in Shandong vary by a factor of four, with thesites located on the coast having the lowest
normalized impacts. This is due to the influence ofsuch factors as the density of population,
meteorological conditions as well as backgroundconcentrations of air constituents.
Mortality Benefits of Alternative Technologies –Taking the Huangtai power plant in Shandong and its
associated coal chain as a reference, the use of low
sulfur coal reduces mortality (expressed in YOLL per
GWh) by a factor of 1.7; and FGD with 95 percent
SO 2 removal efficiency by a factor of 4.4.
Replacement by AFBC gives a reduction factor of 8;
by IGCC a factor of 13; by natural gas CC plant afactor of 52 and by nuclear power plant a factor of 63.
The strong dependence of health damages ontechnology is also reflected in the corresponding
reductions of the estimated “true” costs of electricity
generated by these technologies.
Total Costs Justify Cleaner Technologies – Theexternal costs of the “clean” Shandong electricity
supply scenarios analyzed are typically a factor ofthree to four lower than for the “dirtiest” ones
(depending on whether global warming damages areincluded or not). The total (internal plus external)
costs of environmentally friendly strategies based onclean coal technologies and diversified supply (i.e.
natural gas and nuclear power), are significantly lower
than the total costs of “dirty” and non-sustainablestrategies using conventional pulverized coal
generation. Alternative monetization methods,
considered inappropriate by the international scientificcommunity, can lead to lower estimates of externalcosts. However, the damages avoided by cleaner
technologies exceed the increase in internal costs inall the sensitivity cases analyzed, demonstrating therobustness of the findings. Reduction of major air
pollutant emissions from electricity generation in
China/Shandong, and the associated health andenvironmental damage is feasible, and economicallyand socially justified.
Along with the impacts of the normal operation ofenergy systems, treatment of severe accidents should
be an integral part of any comprehensive comparative
assessment. The assessment of health and otherdamages caused by severe accidents has been thesubjectofextensive
comparative
analyses(Hirschberg et al., 1998; 2003a), not addressed in thepresent paper. In order to give some perspective on
the results we note that the experienced total
damages due to severe accidents in the energy
sector though widely debated are very small incomparison with natural catastrophes but also whencompared with the impacts of air pollution originatingfrom the energy sector. This conclusion is valid also
for the extreme case of Chinese coal chain, exhibiting

Table 3
Estimated uncertainties in terms of geometricstandard deviations for end-point “chronic mortality”.

B

4. Conclusions
A systematic comparison of health impacts
associated with major energy chains and their normal
operation has been carried out. Based on state-ofthe-art approaches this paper provides selected
results of such comparisons, applicable to China. The
following conclusions build on the results presented
here and on the full set of findings from the research
performed.
Overall Health Impacts – Health impacts
associated with air pollution caused by combustion
products are most serious. Fossil power plants(primarily coal- and oil-fired), are major contributors tothese effects, particularly in developing countries. Air
pollution in China has a strongly negative feedbackon the rate of economic growth. Health impacts
dominate the assessed damages. Outdoor air
pollution from all sectors in China resulted in aboutnine million years of life lost (YOLL) in 1998. The
health damages caused by this pollution cost about 67 percent of GDP based on the willingness-to-pay
method, which is comparable to current growth rates.
The power sector contributes about one quarter of thetotal air pollution damage costs in China.
Health Impacts of Specific Pollutants – The major
share of health damage is due to secondary
particulates formed by chemical transformation of
SO 2 and NO x into sulfates and nitrates. Sulfatesdominate damages, so SO 2 is the major contributor,
followed by nitrates and primary particulates. The
estimated physical impacts are sufficiently robust to
be used for decision-making independently of theirmonetary value. For the reference Huangtai plant inShandong, 1998 emissions caused about 25’000
YOLL per year. The average number of YOLL per
tonne of SO 2 emitted in China is almost seven times
higher than the average for the European Union; for
Shandong the corresponding factor is about eleven.
Impacts per tonne of pollutant emitted at different
B

B

B

B

B

B

B

B

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B

Journal of Medical Safety Vol.2 No.1, 2005, October

severe accident fatality rates about 50 times higher
than the corresponding rates in OECD. This finding
underlines the merits of comprehensive and balanced
comparative assessment.

Assessment and Management, Osaka, Universal
Academy Press, Inc., Tokyo, 2000. (An updated
version of this paper was published in “PSI Annual
Report 2000 – Annex IV”).
Hirschberg, S., Heck, T., Gantner, U., Lu, Y.
Spadaro, J. V., Krewitt, W., Trukenmüller, A. andZhao, Y. (2003b): Environmental Impact andExternal Cost Assessment. In: Eliasson, B and Lee, Y.
Y. (Editors), Integrated Assessment of Sustainable
Energy Systems in China, The China Energy
Technology Program, pp. 445 – 586, Kluwer
Academic Publishers, Dordrecht/Boston/London,
2003.
Hirschberg, S., Spiekerman, G., Dones, R. (1998):
Severe Accidents in the Energy Sector. First edition,
PSI Report No. 98-16, Paul Scherrer Institut, Villigen
PSI, Switzerland.
Krewitt, W., Trukenmüller, A., Bachmann T. M.
and Heck T. (2001), Country-Specific Damage
Factors for Air Pollutants. A Step Towards Site
Dependent Life Cycle Impact Assessment. Int. J.
LCA, 6, 199–210 (2001).
Pope C. A. III, Thun M. J., Namboodiri M. M.,
Dockery D.W., Evans J. S., Speizer F. E., Heath C. W.
Jr. (1995): Particulate Air Pollution as Predictor of
Mortality in a Prospective Study of US Adults. Am. J.
Resp. Crit. Care. Med., 151: 669-674.
Pope, C. A. III, Burnett R. T., Thun M. J., Calle E.
E., Krewski, D. Ito, K. and Thurston G. D. (2002):
Lung Cancer, Cardiopulmonary Mortality, and Longterm Exposure to Fine Particulate Air Pollution.
Journal of the American Medical Association (JAMA),
Vol. 287(9): 1132-1141.
WHO (1999): Guidelines for Air Quality. World
Health Organization. Geneva.
http://www.who.int/peh/air/Airqualitygd.htm.

Acknowledgment
Figures 2, 4, 5, 6, and Tables 1 and 3 are reproduced
here from (Hirschberg et al. 2003b) with kindpermission of Springer Science and Business Media.
5. References
Droste-Franke, B., Heck, T., Trukenmüller, A.,
Bickel, P., Friedrich, R. (2002): Impact Assessment
from Air Pollution in Russia – The EcoSense Russia
Version. Contribution of the IER/TTI to the Worldbank
Project ‘Macro Level Estimates of Environmental
Damages in Russia’. Final Report. IER, University of
Stuttgart, Germany.
European Commission (1999): Externalities of Fuel
Cycles, European Commission, DG XII, Science,
Research and Development, JOULE. ExternE Externalities of Energy. Volume 7: Methodology 1998
update. Published by the European Commission,
EUR 19083, ISBN 92-828-7782-5.
Friedrich, R. and Bickel, P. (eds.) (2001):
Environmental Costs of Transport. Springer-Verlag,
Berlin.
Hirschberg, S., Burgherr, P., Spiekerman, G.,
Cazzoli, E., Vitazek, J. and Cheng, L. (2003a):
Assessment of Severe Accident Risks. In: Eliasson, B
and Lee, Y. Y. (Editors), Integrated Assessment of
Sustainable Energy Systems in China, The China
Energy Technology Program, pp. 587 – 660, Kluwer
Academic Publishers, Dordrecht/Boston/London,
2003.
Hirschberg, S., Dones, R., Gantner, U. (2000): Useof External Cost Assessment and Multi-criteria
Decision Analysis for Comparative Evaluation of
Options for Electricity Supply. In: Proceedings of the
5 th International Conference on Probabilistic SafetyP

e-mail: stefan.hirschberg@psi.chP-8-

Journal of Medical Safety Vol.2 No.1, 2005, October

STUDY ON THE EFFECTS OF WATER TREATED WITH DIFFERENT DOSESOF ULTRAVIOLET LIGHT ON CULTURAL PROPERTIES OFBIFIDOBACTERIA, LACTOBACILLI AND BAKERY YEAST
V.K. Ilyin, S.S. Yesiev*, L.V. Rakitskaya , D.A. Tyurina, Z.O. Solovyova,
I.G.Ogorodnikov* E.A. Deshevaya, and V.H. Agnaev
Russian Federation State Scientific Research Center Institute of Biomedical Problems, Russian
Academy of Sciences (RAS IMBP RF SSRC) (Moscow)*Consulting company “Ogorodnikov and Partners”
Abstract
The efficiency of usage of ultraviolet-treated water in cultural media for microorganisms, participated in
production of food stuff was studied.. The activity of growth and development and also different propertiesof lactobacilli, bifidobacteria and bakery yeasts were analyzed. The frequency of genetic transfer ofEscherichia coli markers in liquid nutrient media were estimated.
It was shown that under the influence of ultraviolet treated water the propagation of microorganisms, theirrestoration from liophylised phase is accelerated. The colonies which were grown on the media whichcontain water, treated by ultraviolet, has increased number of colony forming units. The colonies, whichwere grown on agarised media, containing modified water, has a tendency of increased production of someenzymes (bacteriocines, beta-lactamase, hemolysin).
Conjugation, performed in the broth based on water, treated by ultraviolet revealed no changes in plasmids
transfer frequency. The number of colony forming units of yeasts also depended on ultraviolet-treated waterin media, as well as on amount of nutrient substances.
Probably one of the leading mechanisms of acquired modifications of bacterial characteristics, based on
modification of electric conductivity in modified media.
The application of ultraviolet-treated water may be recommended for production of foodstuffs in different
processes, which are used by microorganisms and nutrient media.
Key Words: Microbial cultures, Growth, Pretreatment by UV, Media

Our investigations were aimed at evaluating the
growth properties of micro organisms participating infoods production processes (bread-making, brewing
and sour milk products manufacturing) - bifidobacteria,
lactobacilli and bakery yeast - in conditions of theirculturing on media prepared with the use of water
pretreated with hard ultraviolet irradiation.

Introduction
It is a well-known fact, that some physical factors
cause stimulating effect on biological properties of
micro organisms. For example, factors of increased
pressure of gaseous medium contribute to activationof Gram-positive micro organisms (1,2). Some
evidences confirm that low doses of radiation andchanged solar activity cause optimization of culturalactivity of a number of micro organisms (3).

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Journal of Medical Safety Vol.2 No.1, 2005, OctoberMaterials and methods
Water treatment with ultraviolet light
The necessary amount of water was treated with nonfiltered light produced by a source of ultraviolet
radiation (DRT-400) with a radiant flux that contained
no less than 30 % of ultraviolet quanta with awavelength range of 190 to 250 nm. The luminous
flux with a power of 0.4 W/cm 2 was modeled with theuse of electromagnetic field of an auxiliary device.
Water processing had been carried out until theinternal energy of water increased, according toviscometer readings, two fold.
The following standard culture media were preparedwith the use of water treated with ultraviolet light:- MRS medium for culturing lactobacilli;- Bactofoc medium for culturing bifidobacteria;- LB medium for culturing aerobic test cultures;- meat infusion broth for determining the frequencyof plasmids transfer during conjugation and- wort agar for yeast culturing.
Similar culture media containing water, which had notbeen treated with ultraviolet light, served as control.
P

P

Strains of micro organisms
Collection
strainsofLactobacillus
casei,
Bifidobacterium longum, Pseudomonas aeruginosa,
Escherichia
coli,
Staphylococcus
aureus,
Saccharomyces cerevisiae obtained from RAS IMBPRF SSRC collection were used in the study.

Study of lactobacilli and bifidobacteria
cultures survival in culture media containing
water treated with ultraviolet lightcolony for 24 hours at 37 °C. After incubation, themacro colony was sterilized with chloroform vapor
and covered with semi-liquid agar containing thefollowing cultures:- Staphylococcus aureus;- Pseudomonas aeruginosa (blue pus bacillus);- Escherichia coli (colon bacillus);
The inoculated media were incubated for 24 hours.
After incubation, the antagonistic activity wasevaluated based on the diameter of the zone of
growth inhibition around the macro colony of thelactobacillus strain being tested.

Study of the frequency of genetic materialtransfer with liquid culture medium preparedwith the use of water treated with ultraviolet
lightFresh agarized cultures of Strain J 5-3 E. colicontaining pRl plasmids bearing the determinants ofresistance to broad-spectrum antibiotics belonging tovarious chemical groups (ampicillin, carbenicillin,kanamycin), as well as a fresh agarized culture of
Strain C-600 E. coli sensitive to all antibiotics
excluding nalidixic acid, were incubated in water
treated with ultraviolet light at a temperature of 37 °C.
Incubation in ordinary media at a temperature of
37 °C was used as a control. After incubation, thecultures were re-inoculated on broth and placed in
conditions corresponding to preincubation ones for 24hours. After incubation, conjugation mixtures wereprepared as follows: 1 ml of donor culture containing
1x10 9 CFU/ml were mixed with 1 ml of recipient
culture in the same concentration. The following
conjugation systems were prepared:- donors and an R plasmids recipient grown inwater treated with ultraviolet light and carrying out the
conjugation in water treated with ultraviolet light;- donors and an R plasmids recipient grown inwater treated with ultraviolet light and carrying out the
conjugation in ordinary medium;- donors and an R plasmids recipient grown inordinary medium and carrying out the conjugation inwater treated with ultraviolet;- donors and an R plasmids recipient grown inordinary medium and carrying out the conjugation in
ordinary medium (control).
After the incubation, the mixtures were plated on
culture dishes containing two antibacterial agents (fortransconjugants selection) - one of the antibiotics, towhich the donor strain had shown resistance, andnalidixic acid at a concentration of 100 µg/ml. Afterthe incubation, transconjugant colonies grown on thedishes were counted using the following formula:P

Initially, the cultures being tested had been inlyophilized condition. The cultures were rehydrated,
10-fold titrated in culture media and incubated for 48
hours at 37 °C. Cultures survival was evaluatedbased on the number of grown colonies.

Evaluation of viable cell counts in thecolonies of lactobacilli and bifidobacteria
grown in the culture media containing water
treated with ultraviolet light
Colonies of micro organisms grown in agar wereisolated, diluted in sterile physiologic salt solution andtitrated in test tubes containing the standard growth
medium. Inoculated media were incubated in athermostat at 37 °C for 24 hours; then, counting of thegrown colonies was carried out.

Study of microbial antagonism in culture
media containing water treated withultraviolet light
Culture of the test strain of lactobacilli was grown on
the surface of nutrient agar in the form of a macro- 10 -P

Journal of Medical Safety Vol.2 No.1, 2005, OctoberA
N= ------ (Lg)B
N - frequency of plasmids transfer,
A - number of transconjugant
colonies (CFU/ml),
B - number оf viable cells of therecipient in conjugation mixture (CFU/ml).

Enzymatic activity of cultures grown in
culture media containing water treated withultraviolet light
This activity was evaluated based on production of an
inducible enzyme (beta-lactamase) and a constitutive
enzyme (hemolysin).

Determination of beta-lactamase activity.
Culture of beta-lactamase-producing strain of E. coli
was grown in the form of a macro colony on themedium containing ampicillin in a concentration of 60
mg/ml for 24 hours at 37 °C. After the incubation, themacro colony was sterilized with chloroform vapor,and Escherichia coli culture sensitive to ampicillin waspoured on the surface of the medium. The inoculated
medium was incubated for 24 hours at a temperatureof 37 °C. After incubation, beta-lactamase activity
was evaluated based on the diameter of the zone ofampicillin-sensitive strain growth around the macrocolony of beta-lactamase producing strain.

Results
Study of lactobacillus and bifidobacterium
cultures survival in culture media containing
water treated with ultraviolet light
Data on survival of lactobacilli in culture media
prepared with the use of water treated with ultraviolet
light are presented in Tables 1 to 8. These data show,that the counts of viable lactobacillus colonies
increased approximately 100-fold in conditions ofculturing in growth media containing water treatedwith ultraviolet light. This tendency appeared on thefirst day of culture growth and continued inconsecutive days.

Table 1
Survival of lactobacilli in the growth media containing
water treated with ultraviolet light.

A strain of lactobacilli, which had been stored inlyophilized condition in an ampoule for 13 years, wassuccessfully revivified with the use of the medium
containing water treated with ultraviolet light (Table 2).

Table 2

Determination of hemolysin activity.
Doses of Staphylococcus aureus culture withhemolytic properties were placed on the surface of
5 % blood agar prepared with the use of water treatedwith ultraviolet light. Blood agar prepared with using
the ordinary water served as control. The inoculated
medium was incubated for 24 hours at 37 °C. Afterincubation, activity of hemolysin production was
evaluated.

Revivification of Strain K-25 of Lactobacillus caseiwith the use of growth media containing water treatedwith ultraviolet light (CFU/ampoule).

Evaluation of viable cell counts inlactobacillus and bifidobacterium colonies
grown in nutrient media containing water
treated with ultraviolet light

Evaluation of Saccharomyces cerevisiae
cultural properties
A strain of bakery yeast Saccharomyces cerevisiae
was used in the experiments.
A 0.5 g weight of dry yeast was subjected tosuspending in 10 ml of physiologic salt solution for 5
to 10 minutes. Then, plating was carried out on
culture dishes with Saburo and wort agar nutrient
media prepared with the use of distilled water andwater treated with ultraviolet light. Inoculated media
were incubated in a thermostat at 29 °C for two days.
Simultaneously, number of yeast cells in the original
suspension was counted. Counting the yeast sporesin the suspension was carried out using Goryaev's
counting chamber.

Viable cell counts in colonies grown in nutrient media
containing water treated with ultraviolet light weregreater than the same for ordinary culture media(Tables 3,4).

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Journal of Medical Safety Vol.2 No.1, 2005, OctoberTable 3Viable cell counts in colonies grown in nutrient media
containing water treated with ultraviolet light (CFU/ml)(Experiment No. 1).

for blue pus bacilli, difference in activities did notreach the level of statistical significance (Table 7).

Table 7Microbial antagonism of lactobacilli grown on culture
media prepared with use of water treated withultraviolet light (mm)Table 4
Viable cell counts in colonies grown in nutrient media
containing water treated with ultraviolet light (CFU)(Experiment No. 2).

Meanwhile, the cultures grown on nutrition media
containing water treated with ultraviolet light did not
reproduce their properties during consecutive
passage on ordinary media (Table 5).

Comparative study of the growth propertiesof lactobacillus cultures in nutrition media
containing water treated with ultraviolet lightand neutron flux
We evaluated the effect of water, which had beentreated with another factor, on biological properties oftest cultures; this effect was used as one of controls.
For this purpose, we treated the water with a directed
flux of thermal neutrons, measuring 0.2 neutrons/cm 2
per one second in density, for 14 days. This treatment
corresponded to parameters of cosmic radiation
acting on biologic objects during orbital flight. Resultsof this study are presented in Table 8.
P

Table 5
Survival in ordinary nutrient media of lactobacilli
preincubated in growth media containing water
treated with ultraviolet light.

P

Table 8Survival of lactobacilli in growth media containing
water treated with directed flux of neutrons

Survival of bifidobacteria in the growth media
containing water treated with ultraviolet light wasevaluated in a similar way (Table 6).

Table 6
Survival of bifidobacteria in the growth media
containing water treated with ultraviolet light (CPU)Study of microbial antagonism in nutrition
media containing water treated withultraviolet light
Antagonism of lactobacilli in relation to colon bacilli,
blue pus bacilli and staphylococci also increased in
conditions of lactobacilli growing on media preparedwith use of water treated with ultraviolet light.
Statistically significant difference in activities wasnoted with respect to staphylococcus and E. coli. As

Data presented in this table are wholly compatible
with the data on cultural growth of lactobacilli innutrient growth media containing water treated withultraviolet light. Apart from similarity of the data on
cultural growth, MRS medium color change from lightbrown to light green was noted. The same change incolor of MRS medium was noted in case of treatment
with ultraviolet light. However, consecutive studies
revealeddifferences
betweenproperties
oflactobacillus colonies grown on media prepared withuse of water treated with ultraviolet light and the same
properties in cases of water treated with neutrons,with all the rest conditions of culturing being similar.
Data on viable cells in colonies grown on both typesof media are presented in Table 9 below.

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Journal of Medical Safety Vol.2 No.1, 2005, OctoberTable 9Enzymatic activity of cultures grown innutrient media containing water treated withultraviolet light

Viable cell counts for colonies in growth media
containing water treated with different methods

Data presented in the Table 12 show the absence ofsignificant differences in enzymatic activity of cultures
grown on nutrient media containing water treated withultraviolet light as compared to control.

Study of the frequency of genetic materialtransfer in liquid nutrient medium preparedwith use of water treated with ultraviolet light

Table 12Frequency of genetic material transfer between
mature cells of E. coli and integrity of this material did
not depend on experimental conditions.

Enzymatic activity of cultures grown on media
containing water treated with ultraviolet light

Table 10Frequency of pRl plasmid transfer in nutrient media
containing water treated with ultraviolet light

All isolated clones of their experimental and control
series preserved the whole set of phenotypic featurescontrolled by the plasmid.

Study of Saccharomyces cerevisiae culturalproperties

Table 11
Saccharomyces

cerevisiae

The first series of preliminary experiments included
the studies, which determined the effects of modified
water (MW) treated with ultraviolet light on the countsof colony-forming units of yeast during exit fromanabiosis.

Procedure and results of the study

Primary study of the effects of water treated withultraviolet light on the counts of viable units of
Saccharomyces cerevisiae yeast was carried out.
Results of this study are presented in Table 11.
Study ofproperties

Study of the effects of modified water onkinetics of Saccharomyces cerevisiae yeast
development

culturalAs the presented data show, statistically significant
increase in the viable cell counts was noted in case of
primary inoculation with yeast spore suspension of
medium prepared with use of water treated withultraviolet light as compared to the same counts for
similar inoculation of standard media. Therefore,
structure of water subjected to ultraviolet lightfacilitated the exit from anabiosis of significantly
greater number of cells (but not all cells).
Agreement was reached on carrying out the studies
evaluating the effects of water treated with ultraviolet
light on kinetics of yeast development, with use of thewater for primary suspending the dry mass of yeast
and use of physiologic salt solution as a control.

A strain of bakery yeast used by Bakery Plant No. 21
was chosen for the experiments.
A 0.5 g weight of dry yeast was subjected tosuspending in 10 ml of physiologic salt solution for 5
to 10 minutes. Then, plating was carried out on
culture dishes with Saburo and wort agar nutrient
media prepared with the use of distilled water and
MW. Inoculated media were incubated in a thermostat
at 29 °C for two days.
Simultaneously, number of yeast cells in the original
suspension was counted. Counting the yeast sporesin the suspension was carried out using Goryaev's
counting chamber.
Results of the studies, which have been carried out,
are shown in Table 13.

Table 13
Survival of bakery yeast in growth media containing
water treated with ultraviolet light

As the presented data show, statistically significant
increase in the viable cell counts was noted in case of
primary inoculation with yeast spore suspension of
medium prepared with use of MW as compared to the- 13 -

Journal of Medical Safety Vol.2 No.1, 2005, Octobersame counts for similar inoculation of standard media.
Therefore, primary inoculation with yeast of nutrient
media prepared with use of MW facilitated the exitfrom anabiosis of significantly greater number of cells(but not all cells).
The second series of experiments included thestudies aimed at evaluating the effects of MW on
kinetics of yeast development.

Procedure and results of the study
A strain of bakery yeast used in Bakery Plant Ng. 21
was chosen for these experiments.
A 0.2 g weight of dry yeast was subjected tosuspending for 15 to 20 minutes.
1 and 2 - in 5 ml of physiologic salt solution preparedwith use of MW;
3 and 4 - in 5 ml of ordinary physiologic salt solution.
Design of the experiment:

1

3
2

4

After this, inoculation of solid and liquid nutrient media
was carried out (amount of liquid medium in flasks
was 25 ml):
1 and 3 (in 7-6 B) - wort prepared with the use of
only MW;
2 and 4 (in 7-6 B) - ordinary wort. Inoculation ofsolid nutrient media was carried out with the use ofserial dilutions of original yeast suspension; triple
repetition of plating on dishes was used; inoculationof corresponding media was carried out. Inoculated
media were incubated in a thermostat at 29 °C for twodays. Number of colony-forming units (CPU) counted
for this inoculation corresponded to zero time point ofyeast development curve.
One milliliter of yeast suspension containing 1 x 10 7
to 2 x 10 7 cells was transferred to liquid media
prepared with the use of corresponding solutions (seethe diagram). Total number of cells contained in thesuspension was counted with the use of Goryaev'schamber. Flasks with liquid media and inoculates
were incubated in a thermostat at 29 °C in the courseof the whole experiment. Collecting the samples for
microscopic examination and inoculation was carriedout with obtaining no more than 0.2 ml of material
from each flask at each sampling. Inoculation ofsimilar solid media was carried out (see the diagram).
Description of inoculation procedure is presented
above. Microscopic examination was used forevaluating the condition of yeast culture or monitoring
the process of its development by counting the total
number of cells. This was done for more accurate
P

P

P

P

determining the timing of different stages of yeast
growth.
As a result of the carried out studies, yeast CPU
counts were determined for different conditions andtime points of development. Time course of
Saccharomyces cerevisiae yeast growth in liquid
media is presented in Fig. 1.
Three phases of development were clearly
demonstrated for all the studied variants: lag phase,logarithmic growth phase and stationary phase.
Phase 1 (lag phase) was a period occupied byadaptation to surrounding medium of the yeast cells
introduced by us, as well as their preparation for
budding. For all variants, the budding started at fourhours. However, the daughter cells had not beenmature yet and did not increase the number of CPU.
According to obtained data, this phase of yeast
growth, as well as baseline number of cells exitingfrom anabiosis due to MW and their possible
condition, played an important role.
The greatest yeast CPU count during exit fromanabiosis was noted in the first variant: in this case,
CFU count corresponded to total cell countdetermined with the use of Goryaev's chamber.
Microscopic examination of this suspension carriedout in the course of the first two to three hours
revealed the yeast cells sized 12 to 14 µm (normal
cell size = 6 to 8 (10) µm). Possibly, the membranesof these cells facilitated the intracellular accumulationof substances, whereas the enzymatic systems had
insufficient time for switching to synthesis ofnecessary organelles, which resulted, possibly, in theabsence of multiplication in the cells, which wereready for budding. At three to four hours, the nutrient
liquid contained only those cells, which were adapted
to the given medium, and the budding started.
Phase 2 (logarithmic growth of cells) was a periodcharacterized by highly active multiplication of cells.
For all the studied variants, this period lasted for 8 to
10 hours. In the second, third and fourth variants, therates of multiplication of cells during the initial periodof this phase were nearly equal and corresponded tobaseline number of cells adapted to experimental
conditions. Henceforward, the lagging in formation of
new mature generations of cells was noted; thislagging was especially prominent in the second
variant.
Maximum growth rate of yeast cells during this period
was noted in the fourth variant. The remaining cells
adapted to conditions of the experiment started aquick growth and reached their maximum CPU counts
at 13 to 14 hours.
Phase 3 (stationary phase) was observed at 13 to 14
hours and corresponded to a virtually stopped newcells formation. Microscopic examination carried out
during this period revealed the termination of budding.

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Journal of Medical Safety Vol.2 No.1, 2005, October

Number of cells in diploid stage did not exceed 3 to 2
percent.
By 14 hours of the experiment, number of CFU cells
for all variants increased by 3 to 3.5 orders ofmagnitude (3,000 to 3,500). Therefore, culture media
contained roughly equal amounts of nutrients.
Thus, the conducted studies have shown, that:- use of MW facilitated the exit from anabiosis
condition of the greatest number of yeast cells;- for decreasing the sensitivity of yeast cells to
conditions of culturing in case of using the double
effect of MW (Variant 4: physiologic salt solution
prepared with the use of MW + nutrient medium
prepared with use of MW) ensuring the exit fromanabiosis of the greatest number of cells, culture
medium, temperature, pH, culture medium aeration,etc. shall be selected for their recommending to yeast
manufacturers;- in the studies, which have been carried out, thegrowth in yeast CFU counts did not depend on theuse of MW in culture liquids: it depended only on theamounts of nutrients contained in them.
For using the MW in bread-making and alcohol
production, it is necessary to know the following yeast
parameters: rising capacity, maltase activity andresistance to thermal effects.

Table 14
Presence of additional growth in experimental andcontrol media in conditions of prolonged lactobacillus
cultures exposure.

that is, the modified properties, obviously, are not theconsequences of genetic changes in test objects (themicro organisms being studied). Cultures grown on
nutrient media containing water treated with ultraviolet
light increased the production of bacteriocin.
Therefore, the medium used for growing the objects
being tested becomes aggressive with respect toexternal colonization. This feature was confirmed byresults of prolonged bacterial cultures exposure on
media prepared with use of water treated withultraviolet light and on control media (see Table 19).
In case of exposure of cultures on media containing
water treated with ultraviolet light, contamination withother cultures was absent, whereas the control media
showed an additional growth already on the fourthweek.
One of the important features of nutrient media
prepared with use of water treated with ultraviolet light
was stability of their properties: the gap between
experiments on survival of lactobacilli was twomonths, and the break in cultural activity of microorganisms grown in conditions of experiment andcontrol remained unchanged.
Absence of expressed enzymatic activity ofexperimental and control micro organisms is adisputable result, because other experiments
demonstrated an increase in activity of bacteriocin,
which, like hemolisin and beta-lactamase, is an
exoenzyme. Therefore, these data need verification in
the course of implementing the second stage of theagreement.
Frequency of transfer of genetic markers between
bacteria did not depend on conditions of culturing.
The following possible places of installation of theunits related to the use of culture media and biologic
objects for implementing the process being studied
can be proposed:

A. Sour milk products manufacturing
CONCLUSION
The studies, which have been carried out,
convincingly showed, that the use of water treatedwith ultraviolet light in technologies process resulted
in increased growth of micro organisms used in foods
production biotechnologies. Use of water treated withultraviolet light increases the probability of microorganisms revivification from expired lyophilized
collections and makes it possible tо include archive
micro organisms in production process quickly andproductively, without the need for multiple timeconsuming passage steps. This approach results inquick accumulation of biomass. One more positive
feature of water treated with ultraviolet light is theabsence of reproduction of modified properties by theobjects being tested after withdrawal of this water;

1. Block of reconstitution of industrial strains of
micro organisms from lyophilized condition;
2. Barm preparing block;3. Sour milk products preparing block.

B. Bread-making
1. Block of reconstitution of industrial strains of
micro organisms from lyophilized condition;
2. Barm preparing block;3. Dough preparing block.

C. Preparing the beer yeast
1. Block of reconstitution of industrial strains of
micro organisms from lyophilized condition;
2. Beer yeast preparing block;
3. Beer preparing block.

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Journal of Medical Safety Vol.2 No.1, 2005, Octoberordinary media after exposure in the media containing
water treated with ultraviolet light.

D. Preparing the inoculum for biologicaldegradation of food products and physiologic
waste
1. Block of reconstituting strains and microorganism associations from lyophilized condition;
2. Block of preparing the inoculum;
3. Fermentation block.

E. Preparation of soil bacteria colonies
1. Block of reconstituting the industrial strains of
micro organisms from lyophilized condition;

Conclusion
1. In the process of lactobacillus, bifidobacterium orbakery yeast cultures reconstitution from inactive(lyophilized or dried) condition with the use of culture
media containing water treated with ultraviolet light,
number of colony-forming cells increased roughly 100
fold.
2. This process was accompanied by anapproximately 10-fold increase in the biomass of thecolonies.
3. Culturing lactobacilli in the media containing
water treated with ultraviolet light was accompanied
by increase in bacteriocin production.
4. Carrying out the bacterial conjugation in liquid
media prepared with the use of water treated withultraviolet light was not accompanied by changes in
the frequency of plasmids transfer or changes inplasmid segregation stability.
5. The specified features were not reproduced incase of lactobacilli or bifidobacteria passage toReferences
1. Ilyin V.K., Victorov A.N., Pavlov B.N. et al.
Cultural, biochemical, genetic and ultrastructural
microbial characteristics under high pressure VthInternational Meeting on High Pressure Biology. - St.
Petersburg, 7-9 July 1997.
2. Ilyin V.K., Victorov A.N., Pavlov B.N. et al. Somepeculiarities of human microflora in argon-oxygen
hyperbaricgaseous media IVth joint meeting ofJapanese and European Seminars on High Pressure
Bioscience and Biotechnology. - University of
Heidelberg, Germany, august 30 th – September 3 rd
1998.
3. V.V. Tsetlin, V.A. Bondarenko, A.N. Viktorov et al.
Variatsii radiatsionnoi obstanovki i razvitiya
mikrobnogo soobshchestva na OK MIR v zavisimosti
ot solnechnoi aktivnosti. [Changes in radiation
conditions and microbial community development inorbital complex Mir depending on solar activity] In:
Atlasvremennykh
variatsiyprirodnykh,
antropogennykh i sotsialnykh protsessov. [Atlas of
temporal variations in natural anthropogenic andsocial processes] M.: «Yanus-K» 2002, v.3, pp. 556560. (In Russian)P

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Corresponding to: Prof. Ilyin Viacheslav
Konstantinovich, Institute for Biomedical problems,
Ruusian Academy of Science,
123007 Khoroshevskoye shosse 76a, Moscow
Russia. Tel: (7095)1950025, Fax: (7095)1952253,
E-mail: Ilyin@imbp.ru
HT- 16 -THP

Journal of Medical Safety Vol.2 No.1, 2005, October

MIND/BODY MEDICINE AND STRESS MANAGEMENT
Mutsuhiro Nakao
Teikyo University School of Medicine, Tokyo, Japan
Abstract
The purpose of this review article was to introduce key concepts of psychosomatic medicine or mind/body
medicine, and to show the importance of stress management in clinical practice and daily life. According to
the Japanese National Survey of Health in 2001, 49.0 % of the Japanese people (> 12 years old, n = 109
million) perceived some psychosocial stress.

Such stress was more frequently perceived when they

complained of any physical or psychological symptoms.

A specific illness can be caused, when the

stressors are too intense and persistent, or when persons are vulnerable to the stressors because of theircharacter and ability to adapt. In a clinical population, psychosocial stress is closely related to mind/body
symptoms. Our own study has shown that the reporting of somatic symptoms is a good predictor of major
depression or depression-related symptoms such as suicidal ideation in outpatients attending Japanesemind/body medicine clinics.

Concerning the therapeutic effects of mind/body medicine interventions,relaxation and stress management techniques have been commonly applied for various diseases, such as
anxiety disorders, mild and moderate depression, hypertension, insomnia, and irritable bowel syndrome.
The relaxation response counteracts the harmful effects of stress in such diseases. Medicine can be seen
as a three-legged stool, balanced equally by three healing resources (medication, surgery and self-care).

Key Words: Anxiety, Depression, Mind/body

Medicine, Psychosomatic Medicine, Relaxation, Stress

Management.

1. Recent epidemics of stress in Japan
Stress is the term used to define the body’s
physiological and/or psychological reaction to
circumstances that require behavioural adjustment.
According to the recent Japanese National Survey ofHealth 1) , 49.0 % of the Japanese people perceived
stress in their daily lives. In this survey, the subjects
answered “yes” if they perceived any of the stressorsfor 22 life-related categories including work, family,
neighborhood relations, as well as living-, social-,
financial-, and health related situations.
The
percentage of those with perceived stress was higher
in women (52.6%) than in men (45.1%), and has
continued to increase in both sexes. Work-relatedPP

problem was the most frequent stressor, followed byhealth-related problems and financial problems 1) .
One of the interesting findings of this survey was thatstress was more frequently perceived when patientscomplained of any physical or psychologicalsymptom; 70.4 % of those with such symptoms (n =33 million) reported having stress whereas 41.3% of
those without symptoms (n = 67 million) reported
having stress (p < 0.0001, chi-square test) 1) . These
results suggest that those perceiving psychosocial
stress are likely to complain of mind/body symptoms.
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2. Mind/body medicine in JapanThe symptoms related to psychosocial stress areoften temporary and would disappear with the relief of- 17 -

Journal of Medical Safety Vol.2 No.1, 2005, Octobersuch stress. However, specific illness may be caused
when the suffering stressors are too intense andpersistent. When people are vulnerable to stressbecause of their character and ability to adapt,mind/body illness is likely to occur even if thestressors are mild or moderate. For example, diet
restriction is a common behaviour especially in young
women, but those with eating disorders (e.g. anorexia
nervosa and bulimia nervosa) are known to havecharacteristics such as depression 2) or excessive
adaptation 3) .
The Japanese Society of Psychosomatic Medicine
defines “psychosomatic illness” as any physicalcondition with organic or functional damage affectedby psychosocial factors in the process of its onset ordevelopment 4) . This definition largely corresponds tothat of “psychosocial factors affecting general medical
conditions (code 316.00)” of the Diagnostic andStatistical Manual of Mental Disorders, Third Edition
Revised 5) or Fourth Edition (DSM-IV) 6) , published byAmerican Psychiatric Association. Because the termof ‘psychosomatic’ often sounds like something‘neurotic’ or ‘hypochondriacal’, the term ‘mind/body’has recently been used to describe the association
between mind and body.
Clinicians find the management of mind/body illness
difficult, challenging, and time-consuming. Thus,
patients with mind/body illness are often referred tomind/body medicine clinics along with patients withspecific diagnoses, such as chronic pain, insomnia,
and cardiac conditions.
In Japan seven universities as well as a few regional
hospitals have separate and independent mind/body
medicine departments and almost three thousand
physicians and psychotherapists are the members of
the Japanese Society of Psychosomatic Medicine. In
contrast to Germany 7) , the build-up of the units ofmind/body medicine and psychotherapy was notmade systematically and they were officiallyrecognized with great effort in 1997.
There are no mind/body medicine clinics in mostcountries, and therefore the knowledge of mind/body
medicine needs to be a part of every day work for all
physicians. Also of importance, the organization ofstress care programs involving physicians, nurses,
psychologists, and other health-care specialists would
be beneficial to mind/body medicine activities when
the build-up of mind/body medicine clinics is notpromising in such countries.
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Health Problems, Tenth Edition (ICD-10) 8) but theDSM-III-R or DSM-IV diagnoses for psychiatricdisorders have been recorded up at the Departmentof Psychosomatic Medicine, the University of Tokyo
School of Medicine 9) , which has been one of thecentral institutes leading mind/body practice, researchand education in Japan.
In this institute, the major physical disorders seen
were autonomic nervous dysfunction, irritable bowel
syndrome,
essential
hypertension,
andhyperventilation 9) . [Table 1] Eating disorder, anxiety
disorder, and depressive episodes were alsofrequently seen in this institute.
Concerning
psychiatric diagnoses, the numbers of “somatoform
disorders not otherwise specified” were the largest in
both the DSM-III-R and DSM-IV groups, followed bybulimia nervosa, depressive disorder not otherwise
specified, anorexia nervosa, conversion disorder,
major depression or depressive disorder, panic
disorder with agoraphobia, and psychological factors
affecting the physical or medical condition.
These findings seem to be atypical when comparedwith the previous studies of Western countries. For
example, a study of Italian mind/body clinic showedthat the most frequent mind/body diagnostic finding
was recorded under the rubric of “psychologicalfactors affecting physical condition”, followed byaffective illness, anxiety disturbance, and somatoform
disorders according to the DSM-III criteria. In ourJapanese study 9) , a detailed manual of diagnoses
was made and the physicians specializing in
mind/body medicine discussed the patients’
diagnoses in order to improve the reliability ofdiagnoses. Thus the results reinforce the belief thatboth the DSM-III-R and DSM-IV axis I is largely
inadequate for describing mind/body phenomena 10,11) .
New diagnostic systems for use in mind/bodyresearch are now being developed in Japan 12) . Oneof the most important research areas within
mind/body medicine field is to construct theinternational disease criteria of mind/body illness
conditions.
This has been attempted in somedisorders including irritable bowel syndrome andtension-type headache. For the diagnostic researchin mind/body medicine, there are several key
concepts. Two psychological concepts, alexithymia
and somatosensory amplification, are summarized in
the next section.
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3. Diagnosis of mind/body medicine

4. Concepts for the understanding of themind/body phenomenon

Because international criteria of mind/body illness do
not exist, not only diagnoses by the International
Statistical Classification of Diseases and Related

Alexithymia is a personality construct derived fromclinical observations of patients with mind/bodydiseases, characterized by difficulty distinguishing- 18 -

Journal of Medical Safety Vol.2 No.1, 2005, October

between emotions and bodily sensations 13) . The
Toronto Alexithymia Scale (TAS) and its modified
version, the TAS-R and TAS-20 are among the mostcommon questionnaires to measure this construct 14) .
Somatosensory amplification refers to the tendency toexperience somatic sensation as intense, noxious,and disturbing 15) . The construct of somatosensory
amplitude is helpful in the assessment of theperceptual style of somatization and in theconceptualization of mind/body illness.
The
Somatosensory Amplification Scale (SSAS) was
designedandvalidatedtomeasurethis
phenomenon 16) .
Evidence has suggested that the tendency to developfunctional somatic symptoms is associated withalexithymia 17-19) . Our recent study reported that the
SSAS was significantly correlated with the part of the
TAS, which includes difficulties in identifying anddescribing emotions in the sample with mind/bodyillness 20) .
It makes sense that somatosensory
amplification is linked to alexithymic characteristics
statistically and clinically. The roles of the two
psychological concepts in clinical conditions needfurther study to clarify pathogenesis of mind/bodyillness in the future.
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5. Example of mind/body connection:
somatic symptoms and depression
Somatic manifestation of depression may be a good
example to show mind/body connections of healthconditions. Although depression itself does not meetthe criteria of mind/body illness, somatic symptoms
are common in depression. In some cases, theaffective and cognitive symptoms of depression are
hidden behind a variety of somatic complaints in socalled “masked depression” or “mild depression” 21) .
More than 30,000 people commit suicide annually inJapan, and the number has dramatically increased
with the Japanese economic recession after 1998 22) .
Many employees are forced to work hard because of
the ongoing business restructuring, and someworkers who have committed suicide have been
officially acknowledged as victims of depression
caused by overwork for the past 5 years. There islittle doubt that depression is closely associated withsuicide 23-25) . From the viewpoint of risk management,
it is clinically and economically important to detect
depression earlier because the natural disease
course can be changed by anti-depressive
regimens 26,27) and because earlier detection ofdepression reduces the direct costs of prolonged
depression, including the costs of medications,
hospital cares, and community-based cares; as well
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as the indirect costs, such as loss of earning, lost
productivity, and unemployment 28) .
Considering these situations, our group has tried toclarify the relationship between depression andsomatic symptoms and to use somatic symptoms forthe screening of depression by the reporting ofsomatic symptoms 29-31) . First, the prevalence ofsomatic symptoms and psychiatric characteristics ofmajor depression were examined in a Japanesemind/body outpatient clinic (n = 2,215) 29) . In the total
sample, 91 outpatients (4.1%) were diagnosed with
the DSM-III-R or DSM-IV major depression.
Prevalence of fatigue (86%), insomnia (79%),
nausea/vomiting (50%), and back pain (36%) as wellas the degree of psychosocial stress (DSM-III-R axisIV) were higher (all p<0.05) and scores of global
assessment of psychosocial functioning (DSM-IIIR/DSM-IV axis V) were lower (p<0.001) in the major
depressive patients compared to the remaining
outpatients. The most interesting finding of the study
was the dose-response relationship between theseverity of major depression and the total number ofsomatic symptoms reported. Although it was not
surprising that the scores on Zung’s Self-Depression
Scale (SDS) increased as the severity of major
depression became greater, the total number ofsomatic symptoms increased with the disease
severity as well. [Figure 1] These findings suggestthat the level of depression is closely linked to thereporting of somatic symptoms in a mind/body
medicine population.
Next, 863 outpatients were studied in the same
Japanese mind/body medicine clinic to examine
associations of suicidal ideation with somatic
symptoms and mood states, using the Cornell
Medical Index Questionnaire and the Profile of Mood
States (POMS) 30) . In the study, 266 patients (31%)
reported suicidal ideation and the age- and sexadjusted odds ratios (typically in 1.5-2.5 range) of
somatic symptoms for suicide ideation showedstatistically significant differences (p < 0.05) for 13 of
15 symptoms.
The total number of somatic
symptoms and scores on the POMS depression scalepredicted suicidal ideation (p<0.05) through a multiple
regression analysis.
This suggested that anevaluation of somatic symptoms might be important
to assess the specific symptom of depression andsuicidal ideation in a mind/body medicine population.
In addition to these clinical studies on the connection
between somatic symptoms and depressive
symptoms 29,30) , screening practices for detecting
major depression were evaluated in workers
complaining of somatic symptoms 31) . A total of 1,443
Japanese white-collar employees completed a- 19 -

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Journal of Medical Safety Vol.2 No.1, 2005, Octobermedical symptom checklist (major 12 somatic
symptoms) and were then diagnosed using thestructured clinical interviews of the DSM-IV. There
were 42 cases (2.9%) with major depression in the
total sample. Concerning the 902 subjects without
any somatic symptoms, only one case (0.1%) was
identified as having major depression.
The
prevalence of the disorder was positively associated(p<0.001) with the total number of somatic symptoms,
and the area under the receiver operator
characteristic (ROC) curve was 0.92 for men and0.81 for women, which showed the sensitivity andspecificity of the total number of somatic symptoms
for detecting major depression.
Based on thefindings of these studies, the number of reported
somatic symptoms was found to be a simple anduseful predictor of major depression in both clinicaland working populations.

6. Mind/body medicine in treatment:
biofeedback and hypertension
Clinical effects of biofeedback on hypertension are
discussed in this section as an example of atreatment
strategy
inmind/body
medicine.
Biofeedback is a kind of relaxation training and is partof a group of non-pharmacological therapeutic
procedures that use electronic instruments tomeasure, process, and provide information to patients
regarding their neuromuscular and autonomic
nervous system activity in the form of analogue (orbinary) and visual (or auditory) signals 32-34) . Recent
technical improvements in blood pressure monitoringand data processing make biofeedback more reliable
and comfortable to apply for the treatment ofhypertension. For example, our group developed aneasy-to-use blood pressure biofeedback system incombination with a continuous blood pressure
monitoring device and a personal computer 35,36) , andreported that the system was useful in treating
hypertension including essential hypertension, whitecoat hypertension, and mild hypertension without
organ damage 37-39) .
Because the Joint National Committee on Prevention,
Detection, Evaluation and Treatment of High Blood
Pressure, Seventh Report (JNC-VII) recommends
that hypertension be prevented or managed to reducemorbidity and mortality by the least intrusive means
possible 40) , biofeedback has been used as a secondline non-pharmacological treatment for essential
hypertension in the early stages 41,42) . Concerning
lifestyle modifications, biofeedback training may help
hypertensive patients to become aware of theimportance of controlling blood pressure 43) and ofchanging to a health-promoting lifestyle 44) .
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To assess treatment effects of biofeedback to lower
blood pressure in essential hypertension qualitatively
and quantitatively, a meta-analysis of studied
conducted between 1966 and 2001 was made 45) . A
total of 22 randomized controlled studies with 905
essential hypertensive patients were selected forreview.
Compared with clinical visits or selfmonitoring of blood pressure (non-intervention
controls), the reduction in systolic and diastolic bloodpressures was significantly greater in the biofeedback
intervention by 7.3 [95% confident interval, 2.6, 12.0]
and 5.8 [2.9, 8.6] mmHg, respectively.
Whenbiofeedback intervention was compared with sham or
non-specific behavioral intervention controls, the netchanges of systolic and diastolic blood pressures
were 3.9 [-0.3 to 8.2] and 3.5 [-0.1, 7.0] mmHg,
respectively.
The results of multiple regression
analysis also indicated that biofeedback intervention
decreased systolic and diastolic blood pressure morethan non-intervention controls (P<0.001), but not
more than sham or non-specific behavioral
intervention controls (P>0.05), controlling for theeffects of initial blood pressure. When biofeedback
intervention types were classified into two types:
simple biofeedback group and relaxation-assisted
biofeedback group, only the relaxation-assisted
biofeedback group significantly decreased (P<0.05)
both the systolic and diastolic blood pressures,compared with sham or non-specific behavioral
intervention controls 45) . [Figure 2]
The results suggested that biofeedback was more
effective in reducing blood pressure for essential
hypertension than no intervention. However, thistreatment was suggested to be superior to sham or
non-specific behavioral intervention in essential
hypertension only when combined with otherrelaxation techniques.

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7. General relaxation response
As suggested in the meta-analysis of the biofeedbck
treatment for hypertension, the relaxation training
may be a simple and useful method to calm
persistent hyperactivity of the sympathetic nervous
system. According to the series of works by Herbert
Benson 33,46,47) , the relaxation response is defined as
the physiological and psychological opposite of thearousal or stress response, characterized bydecreased metabolism, blood pressure, rate ofbreathing and heart rate in association with feelingsof calmness and control. From traditional Easternand Western techniques (e.g. pray, zen, yoga, andmeditation), four basic components have been
proposed to bring forth the relaxation response 48) .

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Journal of Medical Safety Vol.2 No.1, 2005, October(1) A quiet environment: Ideally a quiet room withas few distractions as possible is suitable. The quiet
environment contributes to the effectiveness of therepeated word or phrase by making it easier toeliminate distracting thoughts.
(2) A mental device: To shift the mind from logical,
externally oriented thought, there should be aconstant stimulus: a sound, word, or phrase repeatedsilently or aloud; or fixed gazing at an object. The
repetition of the word or phrase is a way to help
trainees break distracting thoughts. The eyes areusually closed when making a repeated sound orword. Attention to the normal rhythm of breathing is
also useful and enhances the repetition of the soundor the word.
(3) A passive attitude: When distracting thoughts
occur, they are to be disregarded and attention
redirected to the repetition or gazing. It is importantto adopt a “let it happen” attitude not to worry how
well the technique is performed. The passive attitude
is perhaps the most important element in eliciting therelaxation response.
(4) A comfortable position: A comfortable posture isimportant so that there is no undue muscular tension.
Some methods call for a sitting position. A few
practitioners use the cross-legged position of yoga.
Trainees should be comfortable and relaxed.
The subjective feelings that accompany the elicitationof the relaxation response vary among individuals.
The majority of people feel a sense of calm and feelvery relaxed. Other descriptions involve feelings ofpleasure, refreshment, and well-being. Regardless ofthe subjective feelings, it has been found that thephysiological changes, such as decreased oxygen
consumption, are taking place 48) .
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8. Systematic stress management program
Based on the regular elicitation of the relaxation
response,
standardized
stressmanagement
programs have been applied for various diseases at
Mind/Body Medical Institute, Harvard Medical School.
Subjects were referred from primary care settings
located within the hospital as well as from clinics
outside the hospital.
The Medical Symptom
Reduction Program is a 10-week program in which
the most outpatients participated 49) . It consists of 9
weekly two-hour sessions and one four-hour sessionthat includes instruction in the elicitation of therelaxation response, cognitive restructuring, coping,stress hardiness, nutrition, and body awareness. To
elicit the relaxation response, patients systematicallypracticed yoga, diaphragmatic breath awarenessexercise, emotional imagery, and meditation
throughout the program. Using these techniques,PP

they were instructed to elicit the relaxation responseat home each day for 20 minutes or twice a day for 10
minutes.
To identify stressors and corresponding physicalsensations and emotions, patients were assigned tocomplete a diary every day throughout the program.
Lectures and group discussions focused onmind/body awareness during the first 5 sessions.
Patients were taught cognitive restructuring skills;
they learned to recognize autonomic thoughts andcognitive distortions associated with stress-related
physical and psychological symptoms. Patients also
received handouts about the nature of thoughts andcognitive distortions, and reviewed them at home.
During the latter 5 sessions, lectures and group
discussions focused on self-control and coping(problem-, emotion-, and physical-focused coping
styles). The lectures included coping with humor,
empathetic communication for social support, andrelapse prevention strategies. Through a series oflectures together with the relaxation training, patients
improved their stress management skills, which
resulted in decreased psychological and somatic
symptoms.
The treatment effect was examined in 1,312
outpatients attending this program 49) . The Medical
Symptom Checklist (12 major symptoms), Symptom
Checklist 90 Revised (SCL-90R), Stress Perception
Scale, and the Health-Promoting Lifestyle Profile
were administered before and after the program. Of
the entire sample, 1,012 patients completed theprogram, and 911 completed the post-treatment
assessment.
Self-reported frequency of medical
symptoms, degree of discomfort, and interferencewith daily activities were significantly reduced as aresult of the program.
Anxiety and otherpsychological distress as measured by the SCL-90R
and stress perception scales also showed significant
reductions. Furthermore, health-promoting lifestylefunctioning significantly improved. High levels of pretreatment anxiety predicted a decrease in the total
number of medical symptoms endorsed. In this study,
it was found that these interventions were effective in
reducing medical symptoms coinciding with an
improvement in anxiety and that high anxiety at
program entry may predict better outcome.
The other studies of this program revealed thatgender is an important factor in relation to the reportof somatic symptoms in stress-related conditions 50) ,the program is suitable for the treatment of both
physical and psychological symptoms among
somatizing patients 51) , and the effectiveness of the
program was not diminished by a few absences- 21 -

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Journal of Medical Safety Vol.2 No.1, 2005, October

although depressed or less educated patients arelikely to drop out from the intervention 52) .
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9. Summary

As suggested by Herbert Benson 48) , medicine should
be as sturdy as a three-legged stool, balanced
equally by three healing resources – medications,
surgery and other medical procedures, and self-careapproaches. Ideally, medicine would be able to callupon self-care for more than half of the everyday
problems that patients experience. All three legs aremandatory and we would draw approximately upon
the medicines and surgeries whenever necessary. In
Japan, the medical expenses have been increasing,and the medical insurance system needs to bereorganized. In this situation, stress management isstrongly required for improvement in quality of life
both physically and psychologically.
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38. Nakao M, Nomura S, Shimosawa T, Fujita T,
Kuboki T. Blood pressure biofeedback treatment,
organ damage, and sympathetic activity in mild
hypertension. Psychother Psychosom 1999;68:341347.
39. Nakao M, Nomura S, Shimosawa T, Fujita T,
Kuboki T. Blood pressure biofeedback treatment ofwhite-coat hypertension. J Psychosom Res
2000;48:161-169.
40. Chobanian AV, Bakris GL, Black HR, Cushman
WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ,
Oparil S, Wright JT Jr, Roccella EJ; National Heart,
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on Prevention, Detection, Evaluation, and Treatmentof High Blood Pressure. The Seventh Report of the
Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure:
the JNC 7 report. JAMA 2003;289:2560-2572
41. Health and Public Policy Committee, American
College of Physicians. Biofeedback for hypertension.
Ann Intern Med 1985;102:709-715.
42. Fahrion SL. Hypertension and biofeedback.
Hypertension 1991;18:663-682.
43. Nakao M, Shimosawa T, Nomura S, Kuboki T,
Fujita T, Murata K. Mental arithmetic is a usefuldiagnostic evaluation in white-coat hypertension. Am
J Hypertens 1998;11:41-45.
44. Japanese Society of Hypertension Guidelines
Subcommittee for the Management of Hypertension.
Hypertens Res 2001;24:613-634.
45. Nakao M, Yano E, Nomura S, Kuboki T. Bloodpressure lowering effects of biofeedback treatment in
hypertension: a meta-analysis of randomized
controlled trial. Hypertens Res 2003;26:37-46.
46. Benson H, Rosner BA, Marzetta BR, Klemchuk
HM. Decreased blood pressure in pharmacologicallytreated hypertensive patients who regularly elicitedthe relaxation response. Lancet 1974:1:289-291.
47. Benson H, Lehmann JW, Malhotra MS,
Goldman RF, Hopkins J, Epstein MD. Body
temperature changes during the practice of g tum-mo
yoga. Nature 1982:295:234-236.
48. Benson H. The relaxation reponse. New York:Morrow, 1975.
49. Nakao M, Fricchione G, Myers P, Zuttermeister
PC, Baim M, Mandle CL, Medich C, Wells-Federman
CL, Arcari PM, Ennis M, Barsky AJ, Benson H.
Anxiety is a good indicator for somatic symptom
reduction through a behavioral medicine intervention
in a mind/body medicine clinic. Psychother
Psychosom 2001;70:50-57.
50. Nakao M, Fricchione G, Zuttermeister PC,
Myers P, Barsky AJ, Benson H. Effects of gender and- 23 -

Journal of Medical Safety Vol.2 No.1, 2005, October

marital status on somatic symptoms of patients
attending a mind/body medicine clinic. Behav Med
2001;26:159-168.
51. Nakao M, Myers P, Fricchione G, Zuttermeister
PC, Myers P, Barsky AJ, Benson H. Somatizationand symptom reduction through a behavioral
medicine intervention in a mind/body medicine clinic.
Behav Med 2001;26:169-176.
52. Nakao M, Fricchione G, Myers P, Zuttermeister
PC, Myers P, Barsky AJ, Benson H. Depression andeducation as predicting factors for completion of
behavioral medicine intervention in a mind/body
medicine clinic. Behav Med 2001;26:177-188.

Table 1
Major ICD-10 diagnoses in a Japanese mind/body
medicine clinic

SDS scores and total number of somatic symptoms inmild (n = 21), moderate (n = 38), and severe major
depression (n = 32).
Values are means with standard errors of the scores,
and p values are based on the Morrison’s multiple
comparison method.

Figure 2
A meta-analysis of effects of biofeedback
interventions on lowering systolic blood pressure inessential hypertension.
The no intervention control group included selfmonitoring of blood pressure and clinical visits. The
sham intervention group included sham or nonspecific behavioral interventions. Values are the net
reductions in systolic blood pressure by biofeedback
intervention.

Figure 1
Total Number of Somatic Symtoms

SDSscores
#
**

80

*

70

**
*

60

*

7

*p<0.05 and**p<0.01

4
3(vs. mildgroup)

2#p<0.05

1(vs.moderategroup)

40
30
20
10

DSM-IV

6
5

50

DSM-III-R

*

0

0

Mild

Moderate

Mild

SevereModerate

SevereFigure 2
Systolic blood pressure
No intervention control studies (n = 11)
Simple biofeedback therapy (n = 6)
Combination therapy (n = 5)

Data was derived from the Psychosomatic Clinic,
Tokyo University Hospital during 1994-1996. OtherICD diagnoses were not specified in the table,
because the percentage of each diagnosis was small(< 3.0%).

Sham intervention control studies (n = 11)
Simple biofeedback therapy (n = 7)
Combination therapy (n = 4)mmHg

Favors treatment

Figure legends
Figure 1

e-mail: mnakao@med.teikyo-u.ac.jp
HT- 24 -

TH

Favors control

Journal of Medical Safety Vol.2 No.1, 2005, October

THE POSSIBILITY TO COMMUNICATE, INTERCHANGE AND SHARE THE
HEALTH AND RISK RELATED VIEW AMONG ORDINARY PEOPLE LIVING
IN DIFFERENT ASIAN COUNTRIESMoriyama, M.*, Tanaka, K., Ushijima, K., Miyake, Y. and Arakawa, M.
Dept. of Public Health, Fukuoka University School of Medicine, Fukuoka, Japan

Abstract
For every people, sharing and learning of risk-related realities in daily life is important, and such sharing isseemed to be substantialized in a visible manner in EU member nations and in North America. However, inAsian countries, the situation is far behind. Lots of barriers (such as culture, politics, geographic location,
language, etc.) exist to prohibit meaningful sharing and learning even within a country as Japan. In thepresent paper, the author aimed to develop a new approach for people to communicate, interchange andshare the life related view of environment, health and risk.
Keywords: Health education, Risk education, Health promotion, Participation, Educational strategy, Asian
perspective

1. What is important as the strategy of healthrisk education?

2. Limit of traditional health education that
focused on a reduction of a specified risk

Recently, many people understand that our living
world is full of risks. Whenever some large scale
accidents and/or disasters happen in other parts ofworld, people recognize that they are not immune tothese accidents and/or disasters. Nowadays, people
are living in a border-less society in relation to risk.
People think that they are able to predict andmanipulate their nearest future and such predictability
and the sense of manipulation accompanies thenotion of risk. However, people’s recognition andmanipulation of their daily life and related risks are not
the same. Some people are under the constantpressure of risks. Some other people can even enjoy
their daily risk. Under such diversity of risk related
recognition, people are not open to share their riskrelated understanding, and such situation iscommonly observed in Japan. Therefore, the goal of
education of health risk management is not merely agiving of risk related information to avoid health risks.
It is more important to empower people to realize,
enjoy, participate and challenge the reality of thisworld by sharing and learning other people’s uniquedaily lives and related views.

Before starting to think about the people’s
empowerment in health risk education, the traditional
style of health education will be looked back. The
most popular style of health risk education used tofocus on some specified risk to improve health status.
In Japan, typical examples can be sought in saltintake-reduction
educationandnon-smoking
education. This type of health risk education used tobe very popular in Japan during 20 th century.
Recently, however, health educators are expected todeal with much more topics and/or risk factors. For
example, Healthy Japan 21, the Japanese overall
health promotion plan 1 , declares over 70 pieces oftargeted values of health promotion. For most ofpeople, however, a single targeted value, such as
decrease of salt intake and/or decrease of smoking, isalready enough to offer meaningful challenges toward
their healthier life. In this instance, how people areable to face and manipulate over 70 pieces oftargeted values instead of a piece of value? Seventyof pieces are too many? This is a typical questionthat annoys not only people but also health educatorsin the ongoing Japanese health promotion
movement 2 . The reality is that, in stead of accepting
meaningful challenges included in Healthy Japan 21,- 25 -

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Journal of Medical Safety Vol.2 No.1, 2005, Octobermany people are overwhelmed by too many targetedvalues. Then, how we will be able to accept multiple
targeted values and its accompanying reality without
losing our positive and meaningful identity to our life?

3. How to establish sound and meaningfulattitude of people toward multiple risks?
Thinking about the present world that is filled withrisks, the starting point of health risk education is 1)
not to be overwhelmed by multiple risks, and 2) toempower people to recognize and challenge toward
their healthier daily life. When people realize thediversity of individual life, the traditional education thatvalue people’s uniformity does not work. Promoting
one’s individuality and one’s uniqueness should be
the basis. However, how are we able to promoteindividuality and uniqueness in the stream of risk
education? The author focused his research todevelop a sensitive inquiry to let people to think about
their life related individuality and uniqueness. The
forerunner of this research is an inquiry to let children
to think about their environment. As the result of thisresearch, the author developed an inquiry called
WIFY (what is important for you?) 3 .
In order to think about the sensitivity of inquiry totouch the life related realty of people, the experienceof WIFY will be served as a reference. At the
beginning of development, the author tried lots ofdifferent inquiries to children about their environment.
Suppose that the following two inquiries (A and B)
were tested. As an inquiry A, the author asked “whatdo you image about environment?”, and a child
replied “Clean water, Dioxin-free foods, andsustainable development“. Then, as an inquiry B, theauthor asked “what do you like about your daily life?”
and the same child replied “Watching TV, going toschool, playing game, playing soccer“. Between
these two replies of A and B, reply A refers toimportant key words of environment. Speaking fromthe viewpoint of technical knowledge level ofenvironment, reply A sounds more preferable. Further
inquiries revealed that the child replied his concerns
related to his previous learning at school.
Incomparison to reply A, reply B does not contain any
technical key words regarding environment. All ofwords in reply B reflect the real concerns of the childin his daily life. Therefore, if the life related realty ofsubject is valued, attitudes to give this type of reply B
should be more encouraged. Then, the author
focused on type B reply, tested and elaborated his
way of asking inquiries, and finally developed WIFY.
Therefore, WIFY is simple and interactive. The basic
question of WIFY is as follows: “Name five matters ofimportance in your life that you would miss if you lostthem.” This same basic question is asked in each of
the following three situations;PP(1) “Imagine your daily life beginning in the morning,
continuing through into the afternoon and evening.”(2) “Imagine your home, your neighbors, yourworkplace and your community.”(3) “Imagine your region, your country as a whole,
your continent, and the planet earth.”

4. Application of WIFY to risk education
After the development of WIFY, the authors started to
ask WIFY for people with diversified backgrounds
regarding health. During the past 3 years, the author
successfully asked WIFY at more than 50 ofoccasions in Japan, 4 in China, 4 in Thailand and 2 inKorea. Conjoint findings were that, by asking WIFY,
people almost always take collaborative attitude andwillingly offer their personal views.
WIFY itself
brought out and enhanced collaborative thinking.
As the three years’ trials of WIFY, the following five
strategies were obtained to nurture the risk related
worldview among people with build-in sense of
sharing reality.

(1) Encourage to reflect daily life.
Encourage people to imagine and reflect their daily
life from one’s own view point.

(2) Avoid using the word “risk”.
The word “risk” so often triggers the negative anddepressive image among people.
It further
suppresses the creative thinking of people.

(3) Starting from importance and continuing to
the loss of importance.
At first, let people to imagine critically important things
and/or issues in their daily life. Then, let people toimage the loss of important issues. This way of
thinking let people to think about the notion of risk
without using the word “risk.”(4) Encourage to shift viewpoints systematically.
Encourage people to shift their viewpoints
systematically to substantiate and enhance theirstanding point to think about health and risk
holistically.

(5) Share and nurture one’s unique views andideas by learning each other.
5. Conclusion
In Western society, each person's individuality anduniqueness is a basis of health education andpromotion. The situation is also true in the area ofrisk management for preventive medicine. However,in a culture in which group based harmony is much
more valued than individuality and uniqueness,rediscovering people's individuality and uniqueness is- 26 -

Journal of Medical Safety Vol.2 No.1, 2005, Octoberan indispensable part in the process toward
meaningful preventive medicine activities such as
health promotion and risk management. Although“individuality” and/or “uniqueness” are important, theycannot be taught in the usual class room. The
present study shows the effectiveness of WIFY to let
people rediscover their individual contexts andresponsibilities regarding their preventive medicine
activities.

References
1. Japanese Committee of Healthy People.
(1999). Kenkou Nippon 21 [Healthy Japan 21].

Tokyo:
Japan Health Promotion & Fitness
Foundation. (In Japanese)
2. Moriyama, M. (2000). What is the objective of
national agenda of health promotion from thestandpoint of community people? Shukan hoken
eisei nyusu, No. 1083, pp10-14. (in Japanese)3.
Moriyama, M., Suwa, T., Kabuto, M. &Fukushima, T. (2001). Participatory assessment of
the environment from children's viewpoints:
development of a method and its trial. Tohoku J. Exp.
Med., 193(2), 141-151.
TE+81-92-801-1011ext.3310 FAX:+81-92-863-8892
e-mail: masakim@fukuoka-u.ac.jp- 27 -

Journal of Medical Safety Vol.2 No.1, 2005, October

ECOCYTOGENETICS: A NEW APPROACH TO PREVENTIVE MEDICINE IN
THE 21ST CENTURY
A. Fucic 1 PhD, J.N. Lucas 2,3 PhD
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1

Institute for Medical Research and Occupational Health, Zagreb, Croatia
Lawrence Livermore National Laboratory, University of California, California
3
American Laboratory Technologies, Inc., Arlington, Virginia
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2
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Abstract
For the last few decades, evaluating genomic damage from environmental and occupational exposure toclastogenic agents has been performed measuring unstable biomarkers. Genetic toxicology relates tochemical and biodosimetry (FISH) offered tools for detecting lifelong cumulative genomic damage and incorrelation with specific cancer development risk. Pressed by the above, a new profession may be
warranted that will unify knowledge of cancer related genomic reorganizations and knowledge of the origin
and mechanisms of genomic damage. We suggest ecocytogenetics as a new discipline in preventive
medicine. Growing database for FISH and cancer registries will provide reliable sources for making cancer
risk assessment for general and occupational exposed populations in the near future. Mounting ethicalquestions combined with societal pressure should cause employers to consider radio- or chemo-sensitive
genetic differences between individuals that put them at health risk in the workforce. Methods used tosupport ecocytogenetics must be accurate and able to analyze large populations. We discuss the accuracyof FISH to measure DNA damage and efforts being made to increase the speed of FISH measurements toroutinely accommodate population-monitoring. We shall show how ecocytogentics may compile andevaluate data to maximize life quality and minimize injury in the living and working environment.
Keywords: genetical toxicology, biodosimetry, clinical cytogenetics, FISH, chromosome aberration, cancer,
health risk assessment

Introduction
Numerical and structural chromosome alterations areformed after exposure to clastogenic (chromosome
breaking) agents. Such agents are natural and man
made radiological isotopes, some chemicals andprocesses associated with natural ageing (1). Similar
chromosomal abnormalities are present in almost all
types of tumour cells. The correlation between genome
damage and malignancy was described at the
beginning of the last century (2). Introduction of
methods like chromosome aberrations assay,
micronucleus assay, sister chromated exchange
frequency, micronucleus assay, comet assay andfinally fluorescent in situ hybridization (FISH) during
the last 30 years facilitated the formation of genetical
toxicology
and biodosimetry.
Both disciplines
represent scientific areas using primarily cytogenetics
in order to investigate genome damage caused bychemical and physical agents in in vitro models, animalmodels and humans. In general, these methods use
peripheral blood lymphocyte as a target cell for
estimation of genome damage. From the beginning ofthese fields, genetical toxicology and biodosimetry
have been related to human population monitoring.
The historical problem for these methods to overcome
has been monitoring of complex exposures including- 28 -

Journal of Medical Safety Vol.2 No.1, 2005, Octoberinter-individual differences (radio- and chemosensitivity).
The difference between action of clastogens agents,
which preferentially damage DNA, and anuegens
agents, which preferentially damage mitotic spindle,
are now satisfactory solved by the application of two
genotoxicological methods, chromosome aberration
assay and micronucleus assay.
About the time that genetical toxicology andbiodosimetry were introduced, 30 years ago, clinicalcytogenetics flourished thanks to introducing of G
banding. G banding facilitated detection of specificstructural rearrangements of chromosomes, whichwere related to specific cancers (or congenital
malformations). The analysis is based on detection ofseveral cells with the same genetical alternations that
represent clones responsible for disease very often
already diagnosed by some other cytological orhematological method. In that way method became atool for confirming the type of cancer, follow up of
therapy results, prognosis of fullcured, analysis ofperipheral blood after bone marrow transplantations
and regular control of patients in a period between
relapses.
However, G banding is very demanding method, timeconsuming and clinical cytogenetician has to be
extremely
experienced
torecognize
bands
translocated from one chromosome to another (3). The
critical markers in clinical cytogenetics are contrary to
genetical
toxicology
exclusivelytranslocations,delecions and inversions which are stable in time andwhich aloud viability and division of cells whichcontains them. Due to difference in staining suchalterations are not visible by chromosome aberrations
assay. The additional difference between this two
methods is that clinical cytogenetics is looking forseveral cells with typical marker by "reading " of G
bands usually analysing up to 50 cells andchromosome aberration assay is looking fordicentrincs, ring chromosomes and breaks which ismuch more easily to detect but which are present
usually one or few of them in 500 cells. G banding was
the only possible methodological approach toaccomplish basic aim of genetical toxicology, the exact
location of stable transmissible genome damage
related with malignancy. For methodological reasons,studies of population exposed to chemical agents orradiation using G bandings are very few (4,5,6,7).
The introduction of fluorescent in situ hybridization(FISH) 15 years ago brought completely new quality inthe biodosimetry and genetical toxicology and toclinical cytogenetics as well. Staining of chromosomeswith different colors by FISH improve recognition ofshort inversions and translocations especially in thoseregions of chromosomes which were by G banding
practically
excludedfromanalysisduetohomogeneously light or dark coloring. In a short timeclinical cytogenetics was able to detect even genes ininterphase cell what was critical in some cases whenmalignant cells were extremely difficult to cultivate.
The benefit of FISH for biodosimetry was immediately
recognized. Dicentrics as unstable markers were
replaced with translocations. The large number ofcells which could be analysed in a short time by FISH
was much less time consuming than G banding. We
believe that merging and overlapping of methods inapplication of clinical cytogenetics, genetical
toxicology and biodosimetry, and the lack ofknowledge of recognition of non-random markers
related to malignancies will forced a closer working
relationship between experts in biodosimetry andexperts in genetical toxicology in order to forge amore united practice of etiology of malignancies due
to exposure to agents from environment andpreventive measures before appearance of firstclinical
symptoms
incriticalpopulations.
Ecocytogenetics, a term suggested by the authors forsuch new discipline, will put in the same
institution/laboratory/department
experts
which
currently divided in completely different areas of
medical practice and governmental institutions andmaking them, unified, significant factor in preventive
medicine. The practice at Oncology departments,
Departments of prenatal and neonatal diagnostics do
not include any information of exposure of children or
adult population on occupational exposure, parental
exposure or hobbies. Collaboration and common
databanks
which
could
be
launchedat
Ecocytogenetic departments will feel a gap between
diagnosis of cancer marker by FISH for clinicalcytogenetics
andmeasuredfrequencyoftranslocations at Institutions registered for monitoringof environmental or occupational exposures by thevery same method.

Methods
Chromosome aberration assay(CA)Blood samples for cytogenetic analysis were
heparinized. Into 0,5 ml samples of whole blood, 8 mlof F-10 medium (GIPCO) containing 20% calf serum
was added. Lymphocytes were incubated fora 48h.
After 45h colchicine was added. Fixation of culturesand preparation of slides were carried out according
to conventional methods (8). Two hundered wellspread and complete metaphases were analysed foreach subject. The results are presented aspercentages.

Sister chromatied exhange frequency (SCE)
Bromodeoxyuridine in a final concentration of 10
mikrogr/ml was added to the previously described cell
culture. The cultures were harvested at 72 h. Fifty
second division cells were scored for SCE (9)- 29 -

Journal of Medical Safety Vol.2 No.1, 2005, October

Micronucleus assay (MN)
Whole blood was cultured fora 44h. Cytochalasin B
was added in final concentration of 3 mikrogr/ml. The
cells were harvested after the total culture period of
72h. Five hundered binucleated lymphocytes wereanalysed per subject (10)Fluorescence in situ hybridization (FISH)
In situ hybridization was performed on slides
prepared as for chromosome aberration assay using
Chromoprobe-M kit containing labelled wholechromosome painting probes fora chromosomes 1,2
and 4(Cytocell, UK) according to the Chromoprobe insitu hybridization protocol.

Subjects
Twelve hundered subjects were analysed bychromosome and cellular abnormalities between
1998 and 2000. The subjects are occupationally
exposed to ionizing radiation (X rays, CS, Sr, Ir, Am,I), chemical substances (vinyl chloride monomer(VCM), antineoplastic drugs, formaldehyde, ethyleneoxide and solvents) and unexposed. Non ofmonitored subjects was accidentaly overexposed byionizing radiation. Film dosimeters showed an annual
dose less than 20 mSv per year for all subjects.
Subjects exposed to VCM belong to two gropus, one
exposed to 300 ppm on average for a period of 20
years and the second one exposed to 50 ppm every
three months over a period of 10 years. For theethylene oxideand formaldehyde contaminants
subjects were exposed to 2 ppm of both gases.

Results
All subjects exposed to ionizing radiation wereanalysed by CA. The highest frequency ofchromosome aberrations was detected in subjects
exposed to ionizing radiation in industrial radigraphy
which is in accordance with literature. This group
showed an increase number of chromatid breaks,
chromosome breaks , acentrics, dicentrics and ring
chromosomes.
In a case of complex exposure to ionizing radiation
and ultrasound in a population of medical personnel
and industrial radiography it is shown by CA and MN
that genome damage is more severe than if subjects
are exposure only to ionizing radiation (11,12).
Subjects exposed to ionizing radiation in industrial
radiography were analysed by FISH at time when
unstable chromosome aberrations were at the level ofcontrol values. However, detected increase frequencyof translocations confirms significance of this methodin evaluation of increased health risk in monitoring.
(13).
In subjects occupationally exposed to chemical
substances CA, SCE and MN were performed

showing that there is a clear correlation between
severity of genome damage and VCM concentrationin the working environment. By G banding method it
is shown that detected break points are related withthose described for hematopoetic malignancies (5,14).
In a case of exposure to antineoplastic drugs absenceof correlation between SCE and MN, and SCE and
CA is clearly shown (14,15).
In all subjects exposed to chemical substances it isshown by SCE the influence of smoking as asynergistic factor.

Discussion
The analysis of 1200 subjects occupationally exposed
to low doses of physical and chemical agents
supports the necessity of biomonitoring of humanpopulation not only after accidental overexposures
but also in a case of exposures to low doses
Detection of genome damage before first clinicalsymptoms is crucial in preventive medicine.
Exposure to polluted environment or to xenobiotics inworking environment is not only related withincreased incidence of cancer development but alsowith development of respitory or cardiovasculardiseases. However, still low curibility of malignat
diseases justify the carcenofobia of mankind and put
carcinogens on the top of priority lists.
It is well known that the cancer is a complex
multistage process, which is not possible to reduce by
the simple presence of detected genome damage liketranslocation or deletion. Aneuploidy, apoptosis,
genome instability, adaptation and interindividual
sensitivity (polymorphism of metabolizing enzimes) toenvironmental agents or age are integrally important.
During last 25 years about 100 genes have beenfound to be involved in neoplasia-associatedchromosomal rearrangements (16) mostly relatedwith haematological disorders while for solid tumours
knowledge is very limited and there is still much more
to be done. The strong advance of diagnostics in thelast decade is based on collaboration between
cytogenetics and molecular genetics.
The position of biodosimetry and genetical toxicology
is at present, in a lobby of oncology and clinicalcytogenetics. Although they exchange data andmethodology more then in the past, there is still no
feedback mechanism by which all three fields benefit.
As a tool for giving new quality to genetical toxicology,
biodosimetry and clinical cytogenetics, we suggest
the need for a new field, "ecocytogenetics".
This field will have as a goal to recognize agents fromenvironment which caused genome damage locatedon certain band related with described neoplasia,
detect clones and suggest further preclinicalsurvilliance within preventive medicine.
The aim of ecocytogenetics should be a further
refinement of karyotyping in subjects occupationally- 30 -S

Journal of Medical Safety Vol.2 No.1, 2005, October

exposed to physical and chemical clastogens,disclosing non-random stable aberrations that maybe
prepared for construction of new FISH probes tomonitor accumulation of rearrangements or detect
residual aberrations after overexposures, to evaluate
the prognostic significance of chromosome aberration
found in exposed person related with development of
neoplastic disease and to suggest gene targeted
therapy in a near future.
Epidemiology and cancer incidence would be in thatway displaced with intermediate cytogenetic markers,
predisposing cancer genes (17) and move fromretrospective to prospective assessment.
Ecocytogenetics will establish "risk profiles" (18) for
individuals and conditions of exposure incorporatinginterindividual variability. Radio and chemo sensitive
subjects will be more easily persuaded to avoid
smoking and be targeted for intensive smoking
cessation programmes, be part of chemoprevention
programmes and be consider as special group forcancer screening programs (18,19).
In detection of marker chromosomes, evaluations
should be limited to follow up studies ofoccupationally or accidentally exposed populations;as only in in vivo conditions effect of additionalparameters such as polymorphism of metabolizing
genes (especially in the case of chemical agents) andrepair capacitiy are present while in vitro study arereflection of more mechanistic approach.
Contrary to previously used genes in genetical
toxicology like hprt gene, aprt gene or HLA genes,
which were selected due to elegance of methods,
ecocytogenetic will have a set of target genes
specifically related to exposure and show a directly
relationship to health risk.
Random and non random distribution of genome
damage caused by environmental agents are still thematterofnumerous
discussions(20,21,22,23,24,25,26,27). It is very importanate insuch studies to be critical regarding the number ofanalysed cells, method and exclusion of those which
are based on analysis of cancer patients in order toavoid instability caused by cancer.However for
eccyogenetics the question of random or non-random
genome damage is irrelevant if the target break points
are determined for certain type of agent(s).
The most frequently detected breakpoints revealedby G banding in the general population andpopulation exposed to low doses of ionizing radiationor chemical agents were detected on 14q11 and 7p13
bands, which are related with malignant lymphomasand leukemias ( 6,5,28,29). Of especial interest are
bands such as 14q32 or 7q35 involved in chronic
lymphoproliferative disorders, acute lymphoblastic
leukemia and non-Hodgkins lymphoma, andrearrangements of TCR and B-cell immunoglobulins
genes (30,31). As a rare example of solid cancers, itis worth mentioned that a gene at band 1p11-13 is
except heamatological malignancy also involved inradiation induced meningiomas ( 32).
Ecocytogenetic will have also strategical importanceas it could launch international ecocytogenetic
network. The main aim of such network would becollecting
cytogenetic data
after occupational,
accidental or environmental exposure in order todevelop critical databanks for reliable prognosis ofhealth risk s . The need for such network has been
expressed (33)S

S

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mutaenic/carcinogenic agents, clinical findings, andbone marrow chromosomes in a acute nonlymphocytic
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8
IAEA, Biological dosimetry. Chromosome
aberration analysis for dose assessment, Technical
Reports Series No 260, International Atomic Energy
Agency, Vienna, 1986:59-63.
9 Perry P, Wolff S. New Giemsa method for
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10 Fenench M, Morley AA. Solution to the kinetic
problem in micronucleus assay. Cytobios 1985;43:233246.

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11 Fučić A, Markučić D, Mijić A, Jazbec AM.
Estimation of genome damage after exposure toionizing rdiation and ultrasound used in industry.
Environ Mol Mutagen 2000;36:47-51.
12 Garaj-Vrhovac V, Fučić A, Kubelka D, Hebrang A.
Assessment of genome damage in occupational
exposure to ionizing radiation and ultrasound. Mutat
Res 1997;395:101-105.
13 Fučić A, Lasan R, Mijić A, Hitrec V. Comparisonof the elimination of unstable chromosome aberrations
an frequency of stable chromosome aberrations in
population involved in industrial radiography. Mutat
Res 2000;483(Supp 1):59.
14 Fučić A, Horvat Dj, Dimitrović B, Mutagenicity ofvinyl chloride monomer in man : Comparison of thechromosome aberrations with micronucleus and sister
chromatid exchange frequencies. Mutat Res Lett
1990;242(1):265-270.
15 Fučić A, Jazbec AM, Mijić A, Šešo-Šimić Dj,
Tomek
R.
Cytogenetic
consequencies
after
occupational exposure to antineoplastic drugs. Mutat
Res 1998;416:59-66.
16 Mitelman F. Recent chromosome aberrations incancer. Mutat Res 2000;462: 247-253.
17 Gerhold T, Rushmore T, Caskey CT. DNA
chips: proising toys have become powerful tools.
Trends Biol Sci 1999;24:168-173.
18 Bartsch H, Studies on biomarkers in cancer
etiology and prevention: a summary and challenge of
20 years of interdisciplinary research. Mutat Res
2000;462:255-279.
19
Neyfakh EA, Alimbekova AI, Suskov II,
Biochemical mecahnisms fora radiogenic cytogenetic
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20 Sachs RK, Awa A, Kodama Y, Nakano M, Ohtaki
K, Lucas JN.
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chromosome aberrations as indicators of large scale
DNA geometry during interphase Rad Research
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21 Natarajan AT, Vyas RC, Weigant J, Curado MP.
A cytogenetic follow-up study of the victims of radiation
victims of a radiation accident in Goiania (Brazil) Mutat
Res, 1991;247:103-111.
22 Lucas JN, Awa A, Straume T, Poggensee M,
Kodama Y, Nakano M, Ohtaki K, Weier U, Pinkel D,
Gray J, Littlefield G. Rapid translocation frequency
analysis in humans decades after exposure to ionizing
radiation. Int J Radiat Biol 1992; 62:53-63.
23 Caspersson T, Haglund U, Lindell B, Zech L.
Radiation-induced non-random chromosome breakage
Exptl Cell Research 1972;75:541-543.

24
Knehr S, Zitzelberger H, Braselmann U,
Nahrstedt U, Bauchinger M. Chromosome analysis byfluorescence in situ hybridization: further indications fora non-DNA-proportional involvement of single
chromosomesinradiation-induced
structuralaberrations. Int J Rad Biology 1996;70:385-392.
25
Luomahaara S, Lindohm C, Mustonen R,
Salomaa S. Distribution of radiation induced exchangeaberrations in human chromosomes 1,2 and 4, Int J
Rad Biol 1999;75:1551-1556.
26 Scarpato R, Lori A, Tomei M, Cipollini M, Barale
R. High prevelance of chromosome 10 rearrangementin human lyphocytes after in vitro X ray irradidation Int
J Rad Biol, 2000; 76: 661-666.
27 Fucic A, Lasan R, Hitrec V,Mijiæ A.,Non-random
genome distribution of translocations formed after
exposure to gamma radiation : the need forstandardization of the FISH method in biodosimetry,
2002, 554-557, Contributed papers, International
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IAEA-CN-91
28 Hsieh WA, Chyiyao NI, Hwang JJ, Fang J-S, Lin
S-P, Lin YA, Huang TW, Chang WP. Evaluation of thefrequencies of chromosomal aberrations in a
population exposed to prolonged low dose-rate 60 Co
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Tawn EJ. The non-random occurence of
exchanges involving chromosomes 7 and 14 in human
lymphocytes: a prospective study of control individuals.
Mutat Res 1988;199:215-220.
30 Kirsch IR, Morton CC, Nakahara K, Leder P .
Human immunoglobulin heavy chain genes map toregion of translocations in malignant B lymphocytes
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33 Suskov II, Glouchtchenko AI, Shevchenko VA,
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TEL ： +38514673188
e-mail: afucic@imi.hr- 32 -

FAX: +3854673303

Journal of Medical Safety Vol.2 No.1, 2005, October

DEATH MAY HAVE ITS BENEFITSTHE ROLE OF FORENSIC PATHOLOGY IN MEDICAL AUDIT
Gilbert Lau
Centre for Forensic Medicine, Health Sciences Authority, Republic of Singapore

Abstract
Background Forensic pathology tends to be perceived as a specialty which deals specifically with sudden,
unnatural and violent deaths, in order to serve the administration of justice. However, autopsy findings haveprofitably been applied to accident prevention, particularly in relation to domestic, industrial andtransportation safety.
Proposal It is proposed that the practice of forensic pathology may be extended beyond its traditional
confines, so as to contribute to improvements in healthcare and clinical risk management.
Materials and Methods

A review of the published and on-going work in support of medical audit,

undertaken by the Centre for Forensic Medicine in Singapore, since 1991.
Observations There was a steady increase in the necropsy-incidence of Coroner's perioperative autopsies
from 2% to 4.4% (p<0.01) during three successive triennia from 1989 to 1997. During this time, the rate ofiatrogenic deaths rose from 15.2% to 28.8% (p<0.02), before falling slightly to 24.4%. From 1995 to 1997,
the proportions of such deaths amongst patients subjected to multiple interventions, or elective procedures,
were more than twice as high as those undergoing single procedures, and those initially classified as
emergencies. 1
PP

Recently, a review of maternal mortality showed a progressive increase in the annual necropsy-based,maternal mortality rate from 1990 to 1999 (range: 0.6-1.9 per 10,000 live-births and still-births). In this study,
amniotic fluid embolism (0.33 per 10,000) and pulmonary thromboembolism (0.21 per 10,000) emerged as
the most common direct causes of maternal death. A quarter (13/51) were perioperative deaths, of which 4
were overtly iatrogenic in nature. Major diagnostic discrepancies occurred in more than half of the direct(20/33) and indirect (9/16) causes of maternal death. 2
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Full medico-legal autopsies conducted on 70 traumatic and 166 natural fatalities (out of a total of 481
deaths), which occurred over the duration of 3 years in a major general hospital, revealed proportionallyfewer discordant clinical diagnoses in the former than the latter group (2/70 vs 24/166; p<0.01); thedifference being accentuated after patients who were dead upon arrival were excluded (2/55 vs 24/96;
p<0.005). It was estimated that in approximately a third of the misdiagnosed and undiagnosed natural
fatalities, a correct diagnosis might substantially have altered the acute management, resulting in improved
patient survival. 3
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Journal of Medical Safety Vol.2 No.1, 2005, October

Enlightening "oddities", such as fatal retroperitoneal haemorrhage complicating percutaneous endoscopic
gastrostomy (PEG), 4 or massive hepatocellular necrosis possibly related to the use of Orlistat, 5 or other
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unusual adverse drug reactions were also encountered.
Conclusion

Considerable benefits might accrue from the forensic examination of post-therapeutic,

maternal and in-patient deaths from major trauma, as well as from unsuspected causes, such as pulmonary
thromboembolism. The potential of forensic pathology as a tool of medical audit merits serious andsystematic exploration.
Key words: Forensic pathology; medical audit; healthcare

Introduction
The very mention of the term "forensic pathology"
evokes images of the lifeless and mutilated victims ofhomicides, suicides, accidents and mass disasters.
Not surprisingly, forensic pathologists tend to be cast,in the popular imagination, as medical detectives
serving the administration of justice. However, thisoverlooks the fact that autopsy findings have informed
accident prevention, particularly in relation todomestic, industrial and transportation safety.
Looking further afield, or rather, closer to home, one
might well ask whether forensic pathology could also
inform clinical practice. It is submitted that, in keepingwith the adage mortui vivis praecipiant (let the deadteach the living), it could certainly be of clinicalrelevance, as well. Indeed, the increasing medical
content of forensic autopsies in some jurisdictions(such as Singapore) has made it imperative forforensic pathologists to provide feedback to clinicians(whether the latter want it or not) on patients on die
unexpectedly, in support of medical audit. In doing so,
forensic pathologists could make significant
contributions to both continuous quality improvement
in healthcare and clinical risk management.

Materials and Methods
The Centre for Forensic Medicine (CFM) of the Health
Sciences Authority undertakes all coronial casework
for the island-republic of Singapore, a city-state with amulti-racial population of circa 4 million. The CFM
processes at total of approximately 3,300 sudden,
unnatural and violent deaths and conducts over 2,000
medico-legal autopsies, annually. Increasing numbersof post-therapeutic deaths have been observed inrecent years.
The published and on-going work undertaken by the
CFM, in support of medical audit since 1993, wasreviewed and summarised. The salient observations
are presented below.

Observations
Perioperative deaths
The systematic collation and review of Coroner's
perioperative autopsies began in 1991, resulting in
the publication of a series of three triennial reports,
which concentrated on deaths following invasive
therapeutic and diagnostic procedures. 1,6,7 There wasa steady and statistically significant increase in the
necropsy incidence of these deaths during theperiods 1989-91, 1992-94 and 1995-97 (2.0%(132/6650),
2.6%(170/6468),
4.4%(270/6074),
respectively; p<0.001). During this time, the rate ofiatrogenic deaths rose from 15.2% to 28.8% (p<0.02),
before falling slightly to 24.4%. Unpublished figuresindicate that the necropsy incidence had increased to
6.7% (418/6274) over the past 3 years (2000-02).
During the 1995-97 triennium, 1 a total of 408
procedures were performed, resulting in an averageof 1.5 procedures per patient, with 37.4% and 4.4%
having undergone ≥2 and ≥4 procedures, respectively.
Most patients (83.3%) were managed by one surgical
specialty and a minority by 2 (15.2%) or 3 (1.5%)
specialties. Of the 66 (24.4%) iatrogenic deaths
identified, almost a third (29.7%) occurred intraoperatively, while 36.2% and 13.7% happened within
and after the first post-operative day, respectively.
This clearly emphasises the importance of conducting
medico-legal autopsies on cases of perioperative
death, even if they should have occurred after the first
24 hours of surgery.
Interestingly, during this period, the proportions ofiatrogenic deaths amongst patients subjected tomultiple interventions, or initial elective procedures,
were 2-3 times as high as amongst those undergoing
single procedures, as well as those initially classified
as emergencies (35.6% vs 16.6% and 33.3% vs13.2%, respectively; p<0.01). Arguably, the firstobservations could be taken as evidence that the riskof iatrogenic injury increases (perhaps exponentially)
with the number of interventions performed, without- 34 -

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Journal of Medical Safety Vol.2 No.1, 2005, October

any implied judgement on their indication or necessity.
However, that the iatrogenic mortality rate forelectives far outnumbered that for emergencies isindeed intriguing and somewhat puzzling, since theformer ought to have had a better survival advantage
and there was no notable difference in the frequencyof multiple interventions between both these groups.
However, it remains a possibility that the elective
procedures may have been more complex than those
performed in emergencies. Where diagnostic
accuracy was concerned, minor and major
discrepancies between clinical and necropsy-based
diagnoses accounted for 21.1% and 1.5% of the 270
cases studied.

Maternal Mortality
Worldwide, well over half a million maternal deaths
occur annually, mostly in developing countries.
Accordingly, maternal mortality ratios in the latter may
be much higher than that in most developed nations(200-1000 vs 10-15 per 100,000 live-births). 8-10
In Singapore, over the period of two decades (198099), the official maternal mortality rates (MMR),
published by the Registry of Births and Deaths, werein the narrow range of 0.0-0.1 per 1,000 live-births
and still-births, thus implying that maternal deaths
were rare to the point of being non-existent in someyears. This inference is in stark contrast to earlier
studies on maternal mortality, amniotic fluid embolism
and pulmonary thromboembolism that havesuggested otherwise. 11-13
Accordingly, a necropsy-based study of maternalmortality, arising from coronial casework, wasundertaken, recently. 2 It showed that, over the past
decade (1990-99), there were 51 maternal deaths outof 20,854 coronial autopsies, with an increasing
necropsy incidence (p=0.046 for linear trend)
accompanied by a cluster of 24 cases during the lasttriennium (1997-99). This was mirrored by a similar
trend in the necropsy-based, estimated MMR(p=0.048), which was, in most years, considerably
higher than the MMR calculated from the publishedfigures (0.4-1.9 vs 0.2-1.4 per 10,000 live-births andstill-births).
Direct causes of maternal mortality accounted for justover half (51%) of all deaths; the leading causes
being amniotic fluid embolism (16/51; 0.33 per
10,000) and pulmonary thromboembolism (0.21 per
10,000), while post-partum haemorrhage (0.06 per
10,000), ectopic pregnancy (0.04 per 10,000),
eclampsia and molar pregnancy (0.02 per 10,000,
each), comprised the rest of this category. This would
imply that mortality from amniotic fluid embolism is atleast 4-8 times higher than that reported in the United
Kingdom, with pulmonary thromboembolism making
an equivalent contribution. 14 While most of theindirect causes (17/51; 0.35 per 10,000) were
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cardiopulmonary in nature, there were also 3 suicides(0.08 per 10,000).
It was observed that the occurrence of fatal amniotic
fluid embolism was evenly distributed throughout the
10-year period. In contrast, maternal deaths from
pulmonary thromboembolism mirrored the overall
trend in the necropsy incidence, which rose steadily
from 1990-95, to peak at 1.56% over 2 consecutive
years (1995-96), before decreasing from 1997
onwards. Indeed, amniotic fluid embolism had atendency to afflict older women, as compared tothose who died from other causes (mean age: 35.1 vs32.2 (95% CI for difference: 0.4-5.8) years; p=0.006)
and that the age difference was particularly marked
when compared to fatalities from pulmonary
thromboembolism (35.1 vs 29.8 (2.9-7.7) years;
p<0.001).
In addition, there were 4 iatrogenic deaths (out of a
total of 13 perioperative deaths). These comprised 2
cases of post-partum haemorrhage from utero-vaginal
rupture, associated with forceps-assisted deliveries;
and 2 cases of resuscitative liver lacerations that
occurred against the background of pulmonary
thromboembolism,
withpulmonarythromboembolectomy having been performed in one
Significantly,
major
diagnostic
ofthese. 15
discrepancies were rife, with correct clinicaldiagnoses being obtained in only two-thirds (20/33)
and half (9/16, excluding a case of suicidal hanging)of the cases of direct and indirect maternal deaths,
respectively. Again, this serves to highlight the needfor full medico-legal autopsies in most cases ofmaternal death.
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Emergency Medicine
A collaborative study with the emergency departmentof a major hospital 3 revealed that of 481 deaths,
which occurred over a 3-year period (1992-94), 89%
were referred to the Coroner. Of the latter, fullmedico-legal autopsies were conducted on 236(55.1%) cases. The clinical diagnostic accuracy fortraumatic deaths was considerably higher than thatfor natural deaths (44/70 vs 36/166; p<0.01); an
observation which was rendered all the morepoignant after patients who were dead on arrival were
excluded (44/55 vs 36/96; p<0.005).
It was further determined that the impact of theinaccurate diagnoses upon the traumatic deaths
would probably have been negligible, as the Injury
Severity Scores (ISS) of these victims were mostly inthe range of 30-75 (where ISS ≥16 denotes a poor
prognosis, while a maximum score of 75 is
considered to be incompatible with life). On the other
hand, in about a third (18/55) of the natural deaths, acorrect diagnosis may have substantially altered theacute management and improved patient survival.

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Journal of Medical Safety Vol.2 No.1, 2005, October

These results have, in fact, prompted the emergency
department in question (to which the author is avisiting consultant), to devise measures aimed at
improving its management of non-traumatic
emergencies.

Medico-legal Vignettes
The following are illustrations of how forensic
pathology could contribute directly to clinical risk
management through the elucidation of the causes of
unexpected post-therapeutic deaths:

Fatal retroperitoneal haemorrhage complicating
percutaneous endoscopic gastrostomy (PEG) 4

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A 93-year-old lady with dementia, neurologicaldysphagia and aspiration pneumonia, died frommassive retroperitoneal haemorrhage after PEG,
performed for feeding purposes. The initial,
unsuccessful attempt at needle puncture of thestomach, under endoscopic guidance, resulted iniatrogenic perforation and laceration of the splenicand superior mesenteric veins close to theirconfluence with the portal vein. It is likely that thedense firous adhesions between the pyloro-antral
region of the stomach and the posterior hepatic
surface had altered the immediate anatomical
relations of the stomach in such a manner as to havepredisposed to these events.

Massive hepatocellular necrosis possibly causedby Orlistat 5

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Orlistat (tetrahydrolipostatin) is a lipase inhibtor which
is used, in conjunction with appropriate dietary control
for the treatment of obesity. It is generally deemed to
be a safe drug, as it mainly exerts a topical action on
the stomach and small bowel, with negligible systemic
absorption and oral bioavailability. Nevertheless,there have been published reports of non-fatal
hepatitis and systemic hypertension associated with
its use. Latterly, there has been a report of a 62-yearold male who died from massive hepatocellularnecrosis, consistent with drug-induced, fulminant
hepatitis, associated with the use of oral Orlistat,presumably taken at the recommended daily dose of
360 mg. It is postulated that this may represent an
idiosyncratic reaction to the drug.

Sudden maternal death associated withresuscitative liver injury 15

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A pregnant lady suffered massive pulmonary
thromboembolism
whilstundergoing
pelvicultrasonography. She was vigorously resuscitated foralmost 2 hours and later underwent emergency
pulmonary embolectomy. At the time of surgery,some 2 litres of blood, emanating from lacerations of
the right hepatic lobe, were found in the peritoneal

cavity. Despite heroic measures, she diedintraoperatively, having developed disseminatedintravascular coagulation. Autopsy demonstrated thepresence of multiple liver lacerations, believed tohave been caused by protracted external cardiac
massage. In addition, the recently gravid uterus wasfound to contain an intrauterine device (an indicationof contraceptive failure).

Discussion
The application of forensic pathology to medical audit,
arguably a keystone of clinical risk management andpreventive medicine, can be a most fascinatingprocess. Indeed, it in not be limited to reviews andretrospective,
clinico-pathologicalsurveys.
Accordingly, the CFM is currently, or will be,collaboratingwithclinical
departmentsoninterventional and prospective studies. These include(a) empiric platelet inhibition in cardiac arrest,
involving a randomized controlled trial to assess theefficacy of thrombolysis with Abciximab (aglycoprotein IIb/IIIa inhibitor) in cases of out-ofhospital cardiac arrest (OHCA); and (b) cardiac arrest
and resuscitation epidemiology in Singapore,
designed to elucidate the epidemiology of pre-hospital
cardiac arrest and treatment in the city state.
Moreover, there has, for some years now, been ongoing collaboration in medial audit and risk
management
activities
withvariousclinical
departments, comprising participation in monthly
mortality and morbidity rounds (emergency medicine);weekly surgical intensive care rounds (multidisciplinary dialogue and consultation); and trauma
audit and medical assurance committees, in addition
to advising health administrators on matters of clinicalquality (as reflected by coronial casework).
Naturally, not all of this is smooth sailing and there is
no shortage of pitfalls, which include the following:
1. The clinical records may be in a mess, at leastfrom time to time.
2. The clinical records may be voluminous andtime consuming to review in some instances.
3. The attending pathologist would have tocontend with an ever expanding lexicon of therapeutic
abbreviations, eg CRRT, CVVH, PICC, BIVAD,
MARS, IABP, VATS, PTCA, etc.
4. The attending surgeon or clinician (of thedeceased patient) is often absent at the autopsy (andthere is only so much that one can glean from thecase notes).
5. A post-therapeutic autopsy can take several
hours to complete (a real imposition on a busy day).
6. The requisite autopsy report may also takehours to write.
7. Important information critical to the conduct of ameaningful autopsy may be missing.

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Journal of Medical Safety Vol.2 No.1, 2005, October

8. The evaluation of a putative case of fatal
adverse drug reaction (ADR) is by no mean easy, if
only on account of polypharmacy and extensive comorbidity, which frequently feature in such cases.
Unpublished data from the CFM, over a recent 5-year
period (1996-2000), showed that of the 22 cases offatal ADR subjected to Coroner's autopsies, 12
patients had taken ≥5 types of medication, while themajority (15) had a variable combination of ischaemic
and hypertensive heart disease, congestive cardiac
failure, end-state renal failure, peripheral vasculardisease, diabetic nephropathy, cerebrovasculardisease, bronchogenic carcinoma and idiopathic
pulmonary fibrosis, just to mention a few.

Conclusion
There can be little doubt that considerable benefits
might accrue from the forensic examination of
perioperative and iatrogenic deaths, maternal deaths,
and in-patient deaths from major trauma, as well as awide range of post-therapeutic deaths. The potentialof forensic pathology as a tool of medical audit
certainly merits serious and systematic exploration.
This, of course, raises the question of who is to audit
the auditors. Perhaps this could be topic of anotherinternational conference. For the present, we might
simply be content to close with a quotation fromCharles Dickens:
Dead, your majesty.
Dead, my lords and gentlemen.
Dead, right reverends and wrong reverends ofevery order.
Dead, good men and women everywhere, born withheavenly compassion in your hearts
And dying thus around us everyday.
Bleak House, 1952-53
Mortui vivis praecipiant

References
1. Lau G. Perioperative deaths: a further
comparative review of coroner's autopsies withparticular reference to the occurrence of fatal
iatrogenic injury. Ann Acad Med Singapore 2000: 29:
486-97.

2. Lau G. Are maternal deaths on the ascent in
Singapore? A review of maternal mortality as
reflected by coronial casework from 1990 to 1999.
Ann Acad Med Singapore 2002: 31: 261-75.
3. Seow E, Lau G. Who dies at A&E? The role offorensic pathology in the audit of mortality in an
emergency medicine department. Forensic Sci Int
1996; 82: 201-10.
4. Lau G. Fatal retroperitoneal haemorrhage: anusual complication of percutaneous endoscopic
gastrostomy. Forensic Sci Int 2001; 116: 69-75.
5. Lau G, Chan CL. Massive hepatocellularnecrosis: was it caused by Orlistat? Med Sci Law
2002; 42: 309-12.
6. Lau G. Perioperative deaths in Singapore: aforensic perspective in a study of 132 cases. Ann
Acad Med Singapore 1994; 23: 351-7.
7. Lau G. Perioperative deaths: a comparative
study of coroner's autopsies between the periods of
1989-1991 and 1992-1994. Ann Acad Med Singapore,
1996; 25: 509-15.
8. Ghosh M K. Maternal mortality. A global
perspective. J Reprod Med 2001; 46: 427-33.
9. Oliver W, Fernandez H. Is safe motherhood anorphan initiative? Lancet 1999; 354: 940-3.
10. Rosenfield A. Maternal mortality in developing
countries. An ongoing but neglected "epidemic".
JAMA 1989; 262: 376-9.
11. Loh F H, Arulkumran S, Montan S, Ratnam S S.
Maternal mortality: evolving trends. Asia-Oceania J
Obstet Bynaecol 1994; 3: 301-4.
12. Lau G, Chui P S P. Amniotic fluid embolism: areview of 10 fatal cases. Singapore Med J 1994; 35:
180-3.
13. Lau G. Pulmonary thromboembolism is notuncommon - results and implications of a five-year
study of 116 necropsies. Ann Med Singapore 1995;
24: 356-65.
14. Why Mothers Die. Report on Confidential
Enquiries into Maternal Deaths in the United Kingdom,
1997-1999. London: 2001.
15. Lau G. A case of sudden maternal deathassociated with resuscitative liver injury. Forensic Sci
Int 1994; 67: 127-32.
e-mail: Gilbert_LAU@HSA.GOV.SG- 37 -

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Journal of Medical Safety Vol.2 No.1, 2005, October

HEALTH PROMOTION, HEALTH EDUCATION AND RISK MANAGEMENT:ASIAN PERSPECTIVES
MAJUMDER M. A. A.
Department of Medical Education, Universiti Sains Malaysia, Malaysia.
SHORT RUNNING HEAD: Health Promotion in Asia

Abstract
By virtue of technological innovations and advances in diagnosis and treatment of common conditions,development of effective immunizations and control of many infectious diseases, and steady declines in
infant mortality, medical science and public health have made great strides in achieving reductions inmorbidity and mortality. Yet, despite these accomplishments and advances, the health burden imposed byunhealthy behaviours (such as improper diet, sedentary lifestyle, and use and abuse of drugs, tobacco andalcohol) as well as by preventable illnesses, injuries, and disability remains substantial, especially in Asian
countries. As a result, patients, physicians, other health care professionals, and the public haveincreasingly recognized the importance of effective strategies for health promotion, health protection, andrisk reduction as being essential to protect, promote, and improve the health of all. This paper seeks tohighlight the health promotion/education and risk management/education endeavours adopted by the Asian
countries to promote healthy lifestyles, combat communicable diseases, confront non-communicablediseases, sustain healthy environment and strengthen health care system.
Keywords: Health promotion, health education, risk management, Asia.

Introduction
Health promotion is a comprehensive social,educational and political action for healthdevelopment. It enhances public awareness of health,fosters healthy lifestyles and community action andempowers people to increase control over thedeterminants of health and thereby improve theirhealth.
The general strategies and approaches required tosuccessfully confront the worldwide deterioration ofhealth were outlined in the First International HealthConference on Health Promotion (Ottawa Charter,1986) and in subsequent conferences (Adelaide,
1988; Sundsvell, Sweden, 1991; Jakarta, 1997;
Mexico, 2000). The Ottawa Charter 1 identifies threebasic strategies for health promotion, viz. advocacy
for health to promote the essential conditions forhealth, enabling all people to achieve the final healthPPpotential and mediating between the different
interests in society in the pursuit of health.
This paper seeks to highlight the healthpromotion/education and risk management/education
endeavours adopted by the Asian countries topromote healthy lifestyles, combat communicablediseases, confront non-communicable diseases,sustain healthy environment and strengthen healthcare system.

Health status in Developing countries
According to World Bank (2003) about 66% of the
Asia countries are either in “low-income economy”(GNI: $745 or less) or in “lower-middle-income
economy” (GNI: $746 - $2,975) 2 , and both groups
altogether constitute developing countries. There is awidening of gap between needs and resources forhealth development in these countries - while thesecountries have 75% of the world’s population, they

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Journal of Medical Safety Vol.2 No.1, 2005, October

have only 17% of the world’s GNP, 5% share ofscience and technology, 15% of energy consumption,
11% of spending on education, 18% of export
earnings, 8% of industry and 6% of world's
expenditure on health 3 .
Developing countries are now experiencing “risktransition” and “demographic transition” along with adouble burden of diseases – the combination of longestablished infectious diseases and newer trends ofchronic, non-communicable diseases. Of the 4.4
billion people in developing countries • nearly three-fifths lack basic sanitation• one-third have no access to clean water• one-quarter lack adequate housing• one-fifth have no access to modern healthservices.
About 1.7 million deaths a year worldwide are
attributed to unsafe water, sanitation, and hygiene,
through infectious diarhhoea. Nine out of ten suchdeaths are in children, and virtually all of the deaths
are in developing countries 4 .
In the World Health Report 2002 of World HealthOrganization (WHO) 4 , ten leading risk factors, interms of the burden of disease they cause, areidentified: underweight; unsafe sex; high bloodpressure; tobacco consumption; alcohol consumption;
unsafe water, sanitation and hygiene; iron deficiency;
indoor smoke from solid fuels; high cholesterol; andobesity. Together, these account for more than onethird of all deaths worldwide and most of these deaths
occur in developing countries.
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burden of many communicable diseases, which
include tuberculosis, poliomyelitis, malaria andleprosy. Adding a new dimension to the alreadychallenging health situation, is the rising trend in theprevalence of non-communicable diseases, such as
cardiovascular and cerebrovascular diseases, cancer
and diabetes mellitus, as well as in the number ofaccidents and injuries. The health situation of theregion is outlined in Box 2.
A society in which human rights are promoted andprotected, and in which human dignity is respected, isa healthy society. Human rights in Asia are affectedby a number of factors, which directly or indirectly
affect health of the population: military governments,
nuclear war between bitter rivals, “War on terror", civil
wars, refugees and internally displaced persons,religious minorities, violence and discrimination
against women and children.

Health Education and Health promotion:
Asian Perspectives

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Asia: Different Context, Different Needs
Asia is the largest continent and also mostheterogeneous of any world’s regions. Cultural,political systems, religions, climates and life styles aredifferent among the countries. In recent years, anumberofdemographic,socio-economic,
environmental, technology and health trends
observed in Asia (Box – 1).
The state of health in developing countries are greatly
affected by a number of external forces:
threats from super power, global warming, undue
influences of international donor agencies, war andconflicts, and economic boom or bust. Internal factors,
which are responsible for lowering of the status of thehealth, are political systems of the countries, politicaluncertainties and conflicts, natural disasters, poor
economicmanagement,
empowerment
andcommunity participation, human rights, high national
expenditure on defense, international blacklisting of
the countries and development plans giving lesspriority to health development.
The South-East Asia region accounts for 5% of the
global land mass and 25% of the world’s population.
The region bears the largest portion of the global

Health education is recognized as the first of the eightelements of primary health care (PHC) in Alma-Ata
Conference in 1978 5 . Since then health education
bureaus under ministry of health are formed in mostof the countries which were equipped with coretrained staff and equipment, and strengthened further
in response to global initiatives by internationalorganizations i.e. UNICEF. A number of initiatives
have been taken to strengthen the health education
programs i.e. institutional training on health education,
development of core human resource development,
community mobilization, utilization of the media,
recruitment of multipurpose voluntary cadre andintersectoral collaboration.
Health promotion is one of the most viable processes
to ensure equitable health development. It can be avery effective preventive measure for a large numberof human illnesses, whether it is mental health,cancers or others. In Asia, health promotion
movement was catalyzed by Ottawa Conference in1986 1 and almost all countries incorporated essential
elements of health promotion into various primary
health care and health educational programs.
Necessary national budgetary allocation was made tointensify focus on "healthy settings approach" andpartnership with other government sectors, NGOs
and the private sectors were established.
Fourth International Conference on Health Promotion
was held in Asia at Jakarta, Indonesia in July 1997 6
and the theme was: “Health Promotion: New Players
for a New Era -- Leading Health Promotion into the
21st Century”. This is the first conference held in adeveloping country and also in Asia and first to
involve private sectors. Conference adopted "TheJakarta Declaration” which identified five priority- 39 -

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Journal of Medical Safety Vol.2 No.1, 2005, Octoberareas, especially aimed at developing countries andsuitable for Asian countries:• Promoting social responsibility for health• Increasing investments for health development• Expanding partnerships for health promotion• Increasing community capacity and empowering
individual• Securing an infrastructure for health promotion.

Health Promotion Experiences in Asia
Improving knowledge and understanding of health isan indispensable step in promoting health-supportive
actions.
Creatingsocial,economic,
andenvironmental conditions that are conducive to healthis also essential. Policy-makers, politicians,
professionals, community leaders and general publicshould have awareness about health matters. WHO 1
set out three principal strategies for promoting healthy
lifestyles:• Advocacy for health and healthy policies• Empowering people for health action• Developing support systems and building
alliances
The health promotion experiences in Asia can begrouped under the abovementioned headings.
Advocacy is a key word in health promotion. In Asia,
initiatives are taken by government, community, NGO,
media, universities and research institutes andinternational agencies to encourage public policies
that are supportive to health. The main aims of
involvement of these stakeholders were to compile
health policy with adequate allocation of resources,
heightened public awareness and community support,
to search for active and equal partners for achieving
health goals, to create public awareness and bringing
about action for health, to provide service, training
and research on priority health issues and to render
manpower, technical and logistic support.
People have the need for and the right to information
on how to maintain, protect and promote health. The
strategies of empowerment equip individuals, families
and communities with right knowledge and skills totake positive action for health and make sound healthchoices. Information, communication and healtheducation are at the heart of empowerment process.
Strategies undertaken by government and otherorganizations to empower people in Asia to promotehealth are outlined below:• Reaching communities
o For prevention, early diagnosis and control of
diseaseso Motivation about family planning, nutrition,water, sanitation, breast feeding, maternal care,eating habits etc.
• Empowering specific population groupsPP

o Women, young people, school-age children,
workers, religious leaders, disadvantage communities
to take control of their own health• Using media
o Promote social marketing/public relationo Using posters, radio spots and documentaries,
stories, folk drama, songs, street plays, puppet show
etc.
Adequate knowledge and desirable attitudes about
health do not necessarily lead to appropriate
practices. The gap between knowledge and practiceis well recognized. To reduce this gap, social support
was sought from community and religious leaders,family members, professionals who have an importantrole in making decisions and in supporting behaviour
patterns conducive to health. Establishment of
support systems and building grand alliances
between and network with groups and agencies weretargeted.

Concerns and challenges for health in Asia
Health education, health promotion and social actions
for health in Asian countries are not achieved astargeted. WHO’s Health for All (HFA) strategy was notrealized fully in many countries, as health was notconsidered to be an integral part of the social andeconomic development. Social justice and humanrights for women, children, workers and minority
groups are not maintained adequately. The concerns
and challenges relating to health promotion andhealth education are listed in Box 3.
Despite the significant achievements in the control ofcommunicable diseases and improvements indrinking water supply and sanitation, Asian countries
are facing an unparalleled challenge of new andemerging infectious diseases 4 . HIV/AIDS, drugresistant malaria and tuberculosis are major causes
for concern. The other challenge concerns noncommunicable diseases and the upsurge in cancer
and cardiovascular diseases and other lifestylerelated diseases, such as diabetes, high bloodpressure, mental depression and suicide. In thiscontext, the increase in tobacco consumption is a
cause for added concern. The link between tobacco
use and cardio-vascular diseases and cancer is wellestablished.
Control of non-communicable diseases (NCD) issomewhat patchy and dependent on special efforts
and interests of some individuals e.g. diabetes control
in Bangladesh, control of cancers in some part ofIndia, control of rheumatic diseases in Indonesia and
CVD control in Myanmar. Only India, Indonesia andThailandhave
someprogresstowards
implementation of integrated NCD prevention
approach.
The newer health problems in Asia are associatedwith disruption to traditional practices in food and- 40 -PP

Journal of Medical Safety Vol.2 No.1, 2005, Octobernutrition due to the rapid urbanization andglobalization, which initiated changing patterns ofconsumption 7 . Presence of under-nutrition and overnutrition is observed within many nations and within
subgroups of those nations. The rapidly growing
epidemic of non-communicable diseases, alreadyresponsible for some 60% of world’s deaths, is clearly
related to changes in global dietary patterns andincreased consumption of industrially processed fatty,
salty and sugary foods 4 . In Japan, alterations inhealth practices, such as decreasing the intake ofsalty foods and strict management of hypertension,
reduces cerebrovascular diseases 8 . On the other
hand, bladder and colon cancer in Japanese are on
the rise due to adoption of Western foods andcooking styles 9 . The magnitude of changing patters ofconsumption can be assessed by the number of the
McDonalds' Restaurants in some of the countries in
Asia (Box- 4).
Globalization increases the smoking rates in Asia.
Sustained campaign, conducted since early 1980s by
USA trade officials to open markets for American
tobacco in Japan, South Korea, Taiwan and Thailand,is also responsible for explosion of smoking rates
across the region. Other causes responsible for suchdeadly practice include: US intervention to
government regulations, multinational corporationsand Western advertising images and governments
consideration of tobacco as a revenue source 7,9 .
In Bangladesh and some parts of the India, arsenic
poisoning in drinking water is a burning healthproblem. More than 90% of people of Bangladesh
depend on tube wells whereas these arecontaminated in 59 of the 64 districts causing 35-75
million people to be affected.
P(iii) Empower most vulnerable to take control of
their own and thereby improve their health.

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Specific strategies for promoting health in Asia areoutlined in Box – 5.
The result of reducing risks and promoting healthy life
will have a wide and lasting social value, even beyond
preventing death and disability, for each country. In
his address to the Fifty-second World Health
Assembly, the Nobel laureate, Dr Amartya Sen
mentioned that “even with low income levels, healthand life expectancy could be improved throughappropriate social support, such as health care,education, etc”. The level of health and well-being in acommunity is largely determined by the way of lifeand behaviour of its members. Health promotion, byfostering healthy lifestyles and community action in
support of health, offers a sound strategy forprotection and improving public health. It should be afundamental component of every health service
based on primary health care in both developed anddeveloping countries.
Health Promotion is everybody’s job, as mentioned by
Gro Harlem Brundtland, Director General, WHO 3 :“Reducing risks to health is the responsibility of
governments- but not only of governments. It rightly
remains a vital preoccupation of all people, in all
populations, and of all those who serve them”. Let’sseize the time! The sooner we get on with it the better.
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References:
1. WHO. Ottawa charter for health promotion.
Health Promotion 1986, 1, iii-v.
2. World Bank Group. Data and Statistics.
Available at: http://www.worldbank.org/ . Accessed
March 24, 2003.
3. WHO. Health Promotion and Community Actionfor Health in Developing Countries. Geneva: World
Health Organization; 1994.
4. WHO. The World Health Report 2002:
Reducing risks, promoting healthy life. Geneva: World
HealthOrganization.
Availableat:
http://www.who.int/whr/en/ . Accessed March 24,
2003.
5. UNICEF/WHO. Primary health care. Report of
the International Conference on Primary health Care,
Alma-Ata, USSR, 6-12 Sept 1978. Geneva: World
Health Organization, 1978.
6. Department of Public health, Government ofSouth Australia. The Jakarta Declaration on Health
Promotion in the 21 st Century . Available at:
http://www.dhs.sa.gov.au/pehs/topics/topic-hpujakarta.htm . Accessed March 24, 2003.
7. Moodie R, Borthwick C, Phongphit S, Galbally
R, Hsu-Hage B H H (2000). Health Promotion
International 2000, Sept 15; 3: 249-257.
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Promoting health in Asia: Future Directions
Health Promotion: Making healthy choices easy,
early and exciting………everywhere. (WHO,
WPRO)

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To promote healthy lifestyles in Asia, focused policy
direction for the development of intensified, innovative,
well-coordinated and effective health promotion
movement is necessary to build national capacities of
the countries. It has been identified that WHO’s mainefforts to improve health are towards medical & publichealth initiatives rather than social directions of the
Ottawa Charter 1 . The strategies for social action as
outlined by WHO 1 are as follows:(i) Advocacy for health to generate public demand,place health issues high on public agenda andconvince policy-makers and decision-makers(ii) Social support for health by involving
community organizations and institutions and healthcare and other related services; and

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Journal of Medical Safety Vol.2 No.1, 2005, October

8. Sakata S, Moriyama M. Japanese dietaryintake of salt and protein: Relating to the strategy ofsalt restriction. Tohoku Journal of Experimental
Medicine 1990; 162 (4), 293-302. (Cited from Bracht
N, editor. Health Promotion at the community level –new advances. Thousand Oaks, California: Sage
publications; 1999. p178).
9. Galbally R, Hsu-Hage BH, Borthwick C. Asianand Western Pacific Approaches to health PromotionCurrent opportunities and programs. In: Bracht N,
editor. Health Promotion at the community level –new advances. Thousand Oaks, California: Sage
publications; 1999. p175-186.

Box – 3
Concerns and challenges of health promotion in Asia

Box – 1
Recent Trends affecting Health in Asia

Box – 4
Number of McDonalds'
countries [2000]

Box – 2
Health profile of Asia

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Restaurants

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Journal of Medical Safety Vol.2 No.1, 2005, October

Box – 5Specific strategies for promoting health in Asia

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Journal of Medical Safety Vol.2 No.1, 2005, October

URMPM PREVIOUS CONFERENCES(From August 2004 to October 2005)

URMPM COMING CONFERENCES(From November 2005 to March 2007 )The 1st American Congress: Advances in Health Risk
Management Strategy and Decision Science
By: Ryoji Sakai, Conference President; URMPM Chair,Prof. Swiss Federal Institute of Technology, Lausanne, etc.
Leda Muñoz Garcia, Conference Honor President; Former
Vice-Rector & Prof. at The University of Costa Rica UCR
Place: University of Costa Rica
Date: August 25-27, 2004
Homepage: http://www.jsrmpm.org/CRConf2004/

World Health Risk Management Center’s Opening
Symposium: ‘Global Transfer of Safety Technology in
Medicine’By Ryoji Sakai
Place: The University of Tokyo, Japan
Date: November 1-3 , 2005
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Russian Special Workshop 'Computer Technology in
Safety Science'
By: Vsevolod Shakin
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The 2nd Asia Pacific Congress:
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URMPM International Forum of Patient Safety'
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T he 1st African Congress:
By: Lazhar Zourgui
Place: Universit de Sfax pour le Sudet, Tunisia
Date: March 28-31, 2006

UU

The 2nd European Congress
By: Kjell Anderson
Place: Stockholm, Sweden
Date: May 14-18, 2006
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By: Natalie Warren, et al.
Place: Montreal Canada
Date: September , 2006
The URMPM Special Conference
Radiation Risk Management
By: SMJ Mortazavi
Place: Iran
Date: October 2006
The 3rd Asia Pacific Congress
By: Som-arch Wongkhomthong
Place: Bangkok, Thailand
Date: 2006
The 2nd World Congress
By: Stephan Morgenthaler
Place: Lausanne, Switzerland
Date: March 2007

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Journal of Medical Safety Vol.2 No.1, 2005, October

URMPM Offices(Head Office)
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Journal of Medical Safety Vol.2 No.1, 2005, October(Publication announcement)
ISSN 1349-3396

Health (URMPM)
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Journal of Medical Safety Vol.2 No.1, 2005, October

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