Current Perspective

Unhealthy Effects of Atmospheric Temperature and

Pressure on the Occurrence of Myocardial Infarction
and Coronary Deaths
A 10-Year Survey: The Lille-World Health Organization MONICA
Project (Monitoring Trends and Determinants in Cardiovascular Disease)
Sandrine Danet, MD; Florence Richard, MD; Michèle Montaye, MD; Stephanette Beauchant, MD;
Brigitte Lemaire, MD; Catherine Graux, MD; Dominique Cottel, MD;
Nadine Marécaux, RD; Philippe Amouyel, MD, PhD

Background—Associations between an increase in coronary heart disease occurrence and low atmospheric temperatures
have been reported from mortality data and hospital admission registries. However, concomitant increases in
noncardiovascular case fatality rates and selection bias of hospital cases may weaken this observation. In this study, we
addressed the question of the relationships between fatal and nonfatal coronary diseases and meteorological variables
in 10-year data (1985 to 1994) collected in a morbidity registry (Lille-WHO MONICA Project) monitoring 257 000 men
from 25 to 64 years of age.
Methods and Results—The impacts of atmospheric temperature (in Celsius) and pressure (in millibars) on daily rates of
myocardial infarction (MI) and coronary deaths were studied. Percentages of variation of event rates according to
meteorological variations were derived from the relative risks estimated with a Poisson regression model. During the
10-year longitudinal survey, 3616 events occurred. Rates of events decreased linearly with increasing atmospheric
temperature. For atmospheric pressure, we detected a V-shaped relationship, with a minimum of daily event rates at
1016 mbar. A 10°C decrease was associated with a 13% increase in event rates (P,0.0001); a 10-mbar decrease ,1016
mbar and a 10-mbar increase .1016 mbar were associated with a 12% increase (P50.001) and an 11% increase
Downloaded from http://ahajournals.org by on January 31, 2020

(P50.01) in event rates, respectively. These effects were independent and influenced both coronary morbidity and
mortality rates, with stronger effects in older age groups and for recurrent events.
Conclusions—This longitudinal study is the first to estimate the attributable effect of meteorological variables on MI
morbidity in population and strongly argues for a systematic fight against cold in cardiovascular disease prevention,
particularly in older ages and after a first MI. (Circulation. 1999;100:e1-e7.)
Key Words: registries n myocardial infarction n temperature, atmospheric n pressure, atmospheric n prevention

T he winter peak of coronary death rates and the increase in

hospital admission rates for myocardial infarction (MI)
in winter have been related to the effect of low tempera-
ture.1–3 Kunst et al4 showed that the relationships between
cold weather and coronary mortality were largely attributable
to the direct effect of exposure to cold temperatures, taking
into account the effects of influenza, air pollution, and season.
However, the associations between coronary events and
meteorological factors reported in mortality studies may be
biased by the increase in case fatality rates observed in winter
and with low temperatures that are related to noncardiovas-
cular complications. Morbidity studies based on hospital
admission data explored only selected events in patients who
survived long enough to be admitted to hospitals. To the best
of our knowledge, only 2 morbidity studies have been
conducted in populations.5,6 These studies, based on 1- and
5-year data from morbidity registries, reported an excess of
coronary deaths with low temperatures. A slight excess of
definite MI rates for temperatures ,0°C was detectable in
Helsinki.5 Conversely, Enquselassie et al6 in Australia failed
to demonstrate any effect of temperature on nonfatal and
incident cases of MI. Finally, meteorological factors other
than atmospheric temperature were less frequently studied.
To clarify the possible associations between coronary
artery diseases and meteorological variables, large
population-based studies are needed, with exhaustive regis-
tration of morbidity and mortality events over long periods of
time in geographical places where meteorological variables
are homogeneous. We addressed the question of relationships
between coronary event rates and meteorological variables in

From Service d’Epidémiologie et de Santé Publique. INSERM U508, Centre Hospitalier et Universitaire, et Institut Pasteur de Lille, Lille, France.
Correspondence to Philippe Amouyel, MD, PhD, INSERM U508, Institut Pasteur de Lille, 1, Rue Calmette, 59019 Lille Cedex, France. E-mail
philippe.amouyel@pasteur-lille.fr
© 1999 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org

1
 2 Circulation July 6, 1999

TABLE 1. Incident, Recurrent, and Fatal Cases of Events and Annual Mean of Daily Mean Atmospheric Temperature and Pressure in
the Lille-WHO MONICA Registry Geographic Area
Atmospheric Temperature, °C Atmospheric Pressure, mbar
MI and Coronary Incident Recurrent Fatal
Year Deaths, n Cases, n Cases, n Cases, n Mean Minimum Maximum Mean Minimum Maximum
1985 353 260 85 132 9.2 214.5 22.5 1016 987 1039
1986 386 282 98 144 9.7 27.2 24.8 1016 986 1038
1987 295 229 64 84 9.5 211.2 24.1 1017 987 1037
1988 295 232 58 96 10.5 21.9 22.3 1016 981 1039
1989 307 232 66 130 11.0 24.1 26.0 1017 964 1044
1990 331 251 69 131 11.2 21.3 27.8 1017 983 1042
1991 319 239 67 150 9.7 29.5 24.3 1018 991 1043
1992 303 236 59 126 10.7 24.8 23.9 1017 986 1041
1993 352 274 66 141 10.3 26.3 23.9 1017 988 1041
1994 373 289 68 147 11.2 23.9 25.9 1016 981 1036
Total 3314 2524* 700* 1281 10.3 214.5 27.8 1017 964 1044
*For 90 events (2.7%), history of MI was missing.

10-year data obtained from the Urban Community of Lille
Ischemic Heart Disease Registry. This epidemiological pro-
gram monitors coronary events in 522 000 men and women
living in the north of France. This morbidity registry collab-
orates to the Multinational Monitoring of Trends and Deter-
minants of Cardiovascular Disease (MONICA) project devel-
oped under the auspices of the World Health Organization
(WHO). The impacts of meteorological variables on daily
incident and recurrent rates of MI, fatal or nonfatal, occurring
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Meteorological Data
Meteorological data of the area were obtained from Meteo-France,
the French national meteorological institute. Daily mean atmospheric
temperature (in Celsius) and daily mean atmospheric pressure (in
millibars) were used.
Statistical Analyses
Statistical analyses were performed with SAS software release 6.11
(SAS Institute Inc). For each age group, means of daily morbidity
rates were calculated for 1°C atmospheric temperature and 1-mbar
atmospheric pressure according to year of occurrence; the annual

between 1985 and 1994 in men 25 to 64 years of age were
explored.
Methods
The Lille-WHO MONICA Registry
Details of the MONICA protocol have been published elsewhere.7
Briefly, the Lille MONICA collaborating center collects exhaustive
standardized data on the incidence of acute MI in a geographically
defined population. This population (257 000 men and 265 000
women, 1990 census) is located in the Nord district of France. Events
occurring in patients 25 to 64 years of age are systematically
recovered from private and public structures and from death certif-
icates. All selected events are reviewed by a trained staff. Every
coronary event must have its apparent onset within the study period
and .28 days from any previous recorded coronary events for each
individual. Any recurrent event in 1 individual occurring after 28
days is counted as a separate event. In the present study, we retained
the definite MI, fatal and nonfatal (WHO-MONICA category 1), and
coronary deaths (fatal WHO-MONICA category 2) registered be-
tween 1985 and 1994. Because of the lower MI rates in women, we
retained events occurring in men only. Three age groups were used:
25 to 44, 45 to 54, and 55 to 64 years. Information on previous
medical history was recorded to determine whether an event was
incident or recurrent. This last information was missing for 90
events. Official statistics of the national census from the French
National Institute of Economical and Statistical Information pro-
vided the demographic data to calculate the occurrence of event rates
by 5-year age groups. The male population of the geographical area,
25 to 64 years of age, increased regularly from 250 013 in 1985 to
262 707 in 1994. During this period, 3616 definite MIs or coronary
deaths occurred in men 25 to 64 years of age. The day, month, and
year of onset of the event were available for all subjects except 8.3%
(day was missing for 302 events). These events were excluded from
analyses.
midyear population of each age group was used as a denominator. To
determine the pattern of distributions, we plotted the mean of daily
event rates (per 100 000) according to the values of the meteorolog-
ical variables. Relations between mean daily event rates and atmo-
spheric temperature or pressure were analyzed for the 3 age groups
separately. Relative risks (RRs) of event occurrence, approximated
by the OR, were computed for 5°C atmospheric temperature and for
10-mbar atmospheric pressure variations by use of a Poisson
regression model. All RRs were adjusted for age group and year of
occurrence. Percentages of variation in event rates according to
meteorological variations were derived from RR. For a given
increase in a meteorological variable, the percentage of variation in
event rates was estimated by 1003(RR21). For a given decrease in
a meteorological variable, the percentage of variation in event rates
was estimated by 1003(12RR)/RR. This approach assumes that
events are rare in the population (as observed for MI and coronary
deaths) and that a log linear relation exists between event rates and
meteorological variables.
Results
The number of total, incident, recurrent, and fatal events per
year and the annual means and ranges of daily atmospheric
temperatures and pressures in the geographical area studied
are shown in Table 1. Among the 3314 events recorded
during the 10 years of the survey for which the day of onset
was available, 568 (17.1%) occurred in men 25 to 44 years of
age, 949 (28.7%) in men 45 to 54 years of age, and 1797
(54.2%) in men 55 to 64 years of age. Most of them (76.2%)
were first events (incident cases), 21.1% were recurrent cases,
and 38.3% were fatal events. Plots of the mean of daily event
rates versus daily mean atmospheric temperature suggested a
linear relationship (Figure 1), whereas a V-shaped relation-
ship was observed for daily mean atmospheric pressure
 Danet et al
Figure 1. Mean of daily event rates per 100 000 individuals according to daily mean atmospheric temperature by age groups: ‚ indi-
cates 25-to-44-year age group; l, 45-to-54-year group; and E, 55-to-64-year group. Dashed and solid lines show event rates pre-
dicted by regression model.
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(Figure 2). For atmospheric pressure, the lowest rate of events
corresponded to 1016 mbar, and linear relationships were
observed for increasing and decreasing pressures from 1016
mbar. In the model, therefore, we introduced atmospheric
pressure as 2 mutually exclusive variables, 1 for atmospheric
pressures ,1016 mbar and 1 for atmospheric pressures
.1016 mbar. The relationships between mean of daily event
rates per 100 000 men according to atmospheric temperature
were plotted for the 3 age groups (Figure 1). In the youngest
age group, no trend could be detected (RR, 0.97; 95% CI,
0.91 to 1.04) (Table 2). Conversely, a significant decrease in
the mean of daily event rates with atmospheric temperature
increase was observed in the 45-to-54-year group (RR, 0.95;
95% CI, 0.91 to 1.00); a much more pronounced effect was
seen in the 55-to-64-year group (RR, 0.92; 95% CI, 0.89 to
0.96). For a 10°C decrease in atmospheric temperature, the
increase in event rates was 13% for all age groups
(P,0.0001), 11% for the 45-to-54-year group (P50.05), and
18% for the 55-to-64-year group (P,0.0001). Consistent
results were obtained for the 3 types of events: fatal, incident,
and recurrent events (Table 2). The impact of atmospheric
temperature was maximum for recurrent cases: a 10°C
decrease in temperature was associated with a 26% increase
in recurrent event rates (P,0.0001) and an 11% increase in
fatal and incident event rates (P50.05 and P,0.001, respec-
tively). A more pronounced effect was observed for older age
groups for all 3 types of events.
The effect of atmospheric pressure on the occurrence of MI
and coronary deaths was also more pronounced in the
Meteorological Factors and Coronary Events 3
45-to-54-year and 54-to-64-year groups. Increases and de-
creases in atmospheric pressure from 1016 mbar were both
associated with increases in daily event rates. When atmo-
spheric pressure was ,1016 mbar, a 10-mbar decrease was
associated with a 12% increase in event rates (P,0.001).
When atmospheric pressure was .1016 mbar, a 10-mbar
increase was associated with an 11% increase in event rates
(P,0.01). Influences of atmospheric pressure on event rates
were consistent for fatal, incident, and recurrent cases. As
with temperature, the impact of atmospheric pressure was
higher in recurrent events and for older ages (Table 2).
Because of the correlation between temperature and atmo-
spheric pressure (r50.24 for low pressures and r520.44 for
high pressures), meteorological events were adjusted for each
other. After this adjustment, the effects of both meteorolog-
ical factors remained significant (Table 3). Thus, a 10°C
decrease in atmospheric temperature was associated with an
11% increase in event rates for MI and coronary deaths
(P50.001), whereas a 10-mbar decrease in atmospheric
pressure ,1016 mbar was associated with a 9% increase in
event rates (P,0.01), and a 10-mbar increase .1016 mbar
was associated with a 5% increase (P5NS).
Discussion
This study is the first to estimate the impact of atmospheric
variables on coronary heart disease morbidity in population
over a long period of time compared with most previous
studies that dealt with mortality rates from routine statistics or
hospital admissions. The rigorous methodology and protocols
 4 Circulation July 6, 1999
Figure 2. Mean of daily event rates per 100 000 according to daily mean atmospheric pressure by age groups; ‚ indicates 25-to-44-
year group; l, 45-to-54-year group; and E, 55-to-64-year group. Dashed and solid lines show event rates predicted by regression
model.
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developed in the frame of the WHO MONICA project
allowed us to quantify over a 10-year period the relationships
between atmospheric temperature and pressure and rates of
coronary events. Atmospheric temperature and pressure in-
dependently influenced MI morbidity and mortality in the
population. A 10°C decrease in atmospheric temperature was
associated with a 13% increase in total coronary event rates,
an 11% increase in incident and coronary death rates, and a
26% increase in recurrent event rates. Concerning atmo-
spheric pressure, the relationship was V-shaped; the rates of
MI and coronary deaths were minimum for 1016 mbar. A
10-mbar decrease in atmospheric pressure ,1016 mbar was
associated with a 12% increase in total coronary event rates,
a 13% increase in coronary deaths, an 8% increase in
incidence rates, and a 30% increase in recurrent event rates.
For atmospheric pressure levels .1016 mbar, a 10-mbar
increase was associated with an 11% increase in total coro-
nary event rates, an 18% increase in coronary deaths, a 7%
increase in incidence rates, and a 30% increase in recurrent
event rates.
The geographical area studied, located on the 50th parallel,
enjoys an oceanic, temperate climate. In this flat region, the
meteorological conditions are homogeneous throughout the
area studied. Thus, daily climatic conditions are similar in all
sites of the area, limiting the variability observed in larger
geographical areas often considered in mortality studies. The
MI and coronary death events were exhaustively collected
and verified. Completeness of registration and standardiza-
tion was ascertained according to the MONICA protocol.7
For 90 subjects (2.7% of the total population), history of MI
was missing. For these patients, however, the monthly distri-
bution of events according to their diagnostic category (MI or
coronary death) was similar to that of the other patients,
suggesting that these missing values did not affect results.
The potential deleterious effect of low temperatures on
cardiovascular mortality and coronary deaths is supported by
numerous studies in various countries. Our results are con-
sistent with these observations. Conversely, the rare morbid-
ity studies conducted in a population failed to demonstrate
any consistent association between the occurrence of incident
and nonfatal MI and low temperatures. The statistical power
of our study allowed us to detect an effect of low tempera-
tures on incident, recurrent, and fatal coronary event rates.
Moreover, convincing arguments about the increase in car-
diovascular risks with cold exist. Increases in blood pressure
and viscosity may underlie the effect of cold on coronary
event occurrence.8,9 Seasonal and temperature variations of
blood pressure, serum lipid, and fibrinogen levels have been
also described.9 –12 Reduced physical activity and diet modi-
fications in winter may also be involved in these
relationships.
Other reports suggested an increase in cardiovascular
mortality associated with heat. Kunst et al4 in the Netherlands
found that 26% of heat-related mortality was due to cardio-
vascular disease, and Pan et al1 in Taiwan described higher
coronary death rates for cold and heat with a minimum death
rate occurring at 26°C. In our study, although the highest
temperature was 28°C, mean daily atmospheric temperatures
of .25°C were unusual (,10 days in 10 years of survey) and
 Danet et al Meteorological Factors and Coronary Events 5

TABLE 2. RRs of Event Occurrence for 5°C Atmospheric Temperature and 10-mbar
Atmospheric Pressure Variations
RR (95% CI)

Atmospheric Low Atmospheric High Atmospheric

Age, y n Temperature (5°C) Pressure\ (210 mbar) Pressure\ (10 mbar)
MI and coronary deaths
25– 44 568 0.97 (0.91–1.04) 0.92 (0.78–1.09) 0.95 (0.81–1.13)
45–54 949 0.95 (0.91–1.00)* 1.12 (1.00–1.25)* 1.10 (0.97–1.25)
55–64 1797 0.92 (0.89–0.96)§ 1.18 (1.09–1.28)§ 1.16 (1.06–1.27)‡
25–64 3314¶ 0.94 (0.91–0.96)§ 1.12 (1.05–1.19)‡ 1.11 (1.04–1.18)†
Fatal cases
25–44 160 1.03 (0.91–1.17) 0.99 (0.73–1.33) 1.01 (0.74–1.38)
45–54 302 1.00 (0.92–1.10) 1.09 (0.89–1.34) 1.13 (0.91–1.40)
55–64 819 0.92 (0.87–0.97)‡ 1.17 (1.04–1.32)† 1.23 (1.09–1.40)‡
25–64 1281¶ 0.95 (0.91–0.99)* 1.13 (1.02–1.24)* 1.18 (1.06–1.31)†
Incident cases
25–44 491 0.95 (0.89–1.02) 0.92 (0.77–1.10) 1.02 (0.85–1.21)
45–54 750 0.96 (0.90–1.01) 1.06 (0.93–1.21) 1.06 (0.92–1.22)
55–64 1283 0.95 (0.91–0.99)† 1.16 (1.05–1.27)† 1.10 (0.99–1.23)
25–64 2524¶ 0.95 (0.92–0.98)‡ 1.08 (1.01–1.16)* 1.07 (1.00–1.16)
Recurrent cases
25–44 65 1.07 (0.88–1.30) 1.00 (0.65–1.53) 0.54 (0.29–1.00)*
45–54 178 0.93 (0.83–1.04) 1.37 (1.09–1.73)† 1.29 (0.98–1.70)
55–64 457 0.85 (0.79–0.91)§ 1.31 (1.12–1.53)‡ 1.43 (1.21–1.69)§
25–64 700¶ 0.89 (0.84–0.94)§ 1.30 (1.15–1.47)§ 1.30 (1.13–1.49)‡
RR was adjusted for year of occurrence.
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*P#0.05; †P#0.01; ‡P#1023; §P#1024.

\Low atmospheric pressure indicates lower than 1016 mbar; high atmospheric pressure, higher than 1016 mbar.
¶Adjusted for year of occurrence and age group.

did not allow us to confirm this observation on morbidity
rates.
The consequences of atmospheric pressure on cardiovas-
cular diseases have been studied less frequently, probably
because most studies analyzed only monthly or seasonal
variations of event rates. Indeed, variability of monthly
atmospheric pressure is weaker than daily variations, often
leading to inconclusive results. One study reported higher
daily rates of MI cases with atmospheric pressures ,1000
mbar.5 Chen and colleagues13 found an association between
intracerebral hemorrhage and atmospheric pressures .1022
mbar, whereas Lejeune et al14 found that atmospheric pres-
sure was lower the day before the occurrence of subarachnoid
hemorrhages. Finally, 1 hospital-based study showed that
atmospheric pressure might be a discriminant factor between
MI, more often associated with low pressures, and intracere-
bral hemorrhage, more often associated with high pressures.15
The V-like relationship observed in the present study needs to
be confirmed. However, the consistency of our results regard-
less of category, the detection of the lowest rate of events at
the point that commonly defined low and high atmospheric
pressures, and the persistence of the effects after adjustment
of atmospheric temperature strongly argued for a specific and
independent effect of atmospheric pressure on MI mortality
and morbidity. A weak negative effect of atmospheric pres-
sure (range, 720 to 750 mbar) on blood pressure levels has
been reported in hypertensive patients who did not respond to
treatments16; this association between atmospheric pressure
and a common risk factor of coronary artery disease may
offer a clue in our exploration of a biological mechanism
underlying the effect of atmospheric pressure on coronary
heart disease.
We reported stronger effects of meteorological variables
on recurrent case rates. This group of cases is composed of
patients who resisted a first MI. In this subgroup, the control
of classic risk factors of MI with secondary prevention, even
limited,17 and development of a chronic cardiac disease
afterward may explain their increased vulnerability to other
less common noncontrolled risk factors such as meteorolog-
ical variables. The increasing influence of atmospheric tem-
perature and atmospheric pressure as age increased in all
subgroups has previously been described for temperature.1
The predominance of the effects of the meteorological factors
after 55 years of age could be explained both by the impact of
strong genetic determinants of MI before 55 years of age18
and by body temperature control mechanisms becoming less
efficient with age.19
Finally, our results indicating a relationship between me-
teorological variables and coronary event rates, particularly
for recurrent event rates, strongly suggest that fighting against
 6 Circulation July 6, 1999

TABLE 3. RRs of Event Occurrence for 5°C Atmospheric Temperature and 10-mbar
Atmospheric Pressure Variations Adjusted for Each Other
RR (95% CI)

Atmospheric Low Atmospheric High Atmospheric

Age, y n Temperature (5°C) Pressure\ (210 mbar) Pressure\ (10 mbar)
MI and coronary deaths
25– 44 568 0.96 (0.90–1.03) 0.90 (0.76–1.07) 0.92 (0.77–1.10)
45–54 949 0.96 (0.91–1.01) 1.10 (0.97–1.23) 1.06 (0.93–1.21)
55–64 1797 0.94 (0.90–0.97)‡ 1.14 (1.05–1.24)‡ 1.10 (0.99–1.20)
25–64 3314¶ 0.95 (0.92–0.98)‡ 1.09 (1.02–1.16)† 1.05 (0.98–1.13)
Fatal cases
25–44 160 1.04 (0.91–1.19) 1.01 (0.74–1.37) 1.05 (0.75–1.46)
45–54 302 1.03 (0.93–1.13) 1.11 (0.89–1.37) 1.15 (0.91–1.46)
55–64 819 0.94 (0.89–1.00)* 1.13 (1.00–1.28)* 1.17 (1.01–1.34)*
25–64 1281¶ 0.97 (0.93–1.02) 1.11 (1.00–1.23)* 1.15 (1.03–1.29)*
Incident cases
25–44 491 0.94 (0.88–1.02) 0.89 (0.74–1.07) 0.97 (0.80–1.16)
45–54 750 0.96 (0.90–1.02) 1.04 (0.90–1.19) 1.02 (0.88–1.19)
55–64 1283 0.96 (0.92–1.00) 1.13 (1.03–1.25)† 1.06 (0.95–1.19)
25–64 2524¶ 0.96 (0.93–0.99)† 1.06 (0.98–1.14) 1.03 (0.95–1.12)
Recurrent cases
25–44 65 1.02 (0.83–1.25) 1.01 (0.65–1.57) 0.55 (0.29–1.04)
45–54 178 0.97 (0.85–1.10) 1.35 (1.06–1.72)* 1.25 (0.93–1.68)
55–64 457 0.88 (0.81–0.95)‡ 1.23 (1.05–1.44)† 1.27 (1.06–1.52)†
25–64 700¶ 0.91 (0.86–0.97)† 1.24 (1.09–1.41)‡ 1.20 (1.03–1.39)*
RR was adjusted for year and other meteorological factor.
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*P#0.05; †P#0.01; ‡P#1023.

\Low atmospheric pressure indicates lower than 1016 mbar; high atmospheric pressure, higher than 1016 mbar.
¶Adjusted for year, other meteorological factor, and age group.

cold is important in cardiovascular prevention. Individual
prevention with clothes suited to cold weather in winter and
collective prevention with the improvement of heat insulation
of living quarters may be implemented. This advice is
supported by the results of 2 recent studies. The Eurowinter
group observed that increases in mortality rates with de-
creases in temperatures were higher in warmer regions of
Europe than in colder. This may be due to inadequate
individual and collective protection against cold in those
countries with mild winters.20 Moreover, Seretakis et al21
showed that changes in seasonal patterns in coronary mortal-
ity in the United States were compatible with gradual expan-
sion of adequate heating and use of air conditioning. Other
population studies in different countries based on similar
designs should be developed to further confirm and detail the
influences of meteorological variables on coronary heart
disease occurrence. These reports should emphasize the
importance of adequate temperature conditions as prevention.
Acknowledgments
We thank Chantal Steclebout and Nadège Parsy for helpful data
management and Annie Bingham (INSERM U258, Paris) for data
validation. The ischemic cardiac registry of Lille is certified by the
Comité National des Registres (French Ministry of Health) and
supported by grants from the Institut National de la Santé et de la
Recherche Médicale, Direction Générale de la Santé, Centre Hospi-
talier et Universitaire de Lille, Conseil Régional du Nord et du Pas
de Calais, and the Institut Pasteur de Lille.
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