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Endogenous microbial dissemination following severe burns in rats
Burns (1986) 12,325-329
Printed in Great Britain
325
Endogenous microbial dissemination following severe burns in rats Ma Li, Xiao Guang-Xia, Burn Center, Southwestern
Wang De Wang and Li Ngao Hospital, Chongqing, Sichuan, China
Summary This study suggests thot dnmagc to the intestinal lining. ;I” important mcchanic;tl harrier against hxtcrial invasion. is the mSn l’xtor leading to the dissemination of endogcnous microhcs. Reduced phagocytic activity of Kupllcr cells and compromised opsonic function ;dso ;~ppc;tr to contrihutc to the process.
INTRODUCTION ONI, of the most
serious complications encountered during the treatment of burn patients is generalized infection. Large wound surface areas serve as portals of entry for a wide variety of infective microorganisms, but might there not be other ways in which translocation of bacteria and generalized infection can occur? This study was undertaken in order to determine whether postburn dissemination of intestinal microbes can occur. and if so. to elucidate the pathological mechanisms involved.
use in indirect dies.
immunofluorescence
staining stu-
Infection and burning of the animals One hundred adult male rats weighing 23(~3OOg were randomly divided into five groups of 20 animals each, the members of each group being killed and examined at either 3. 6, 12, 24 or 48 h after injury. Each group included IO burned rats and IO unburned control rats. Twelve hours before burning all of the rats received the bacterial suspension (0~7ml/l0og body wt) by means of gastric intubation under ether anaesthesia. Thereafter. the animals were given neither food nor water. Half of the animals in each group then received a 30 per cent TBSA full thickness flame burn. All the rats were then killed and examined at various post-burn times, depending on the group to which they belonged.
Preparation of histological samples MATERIALS AND METHODS Preparation of antimicrobial serum Type I P.sc~fomonus aerugino.sa bacteria isolated from infected wounds of burn patients were cultured on blood agar plates at 37°C for 24 h. then washed with normal saline. Bacterial suspensions containing 9X IO’ microorganisms/ml were prepared for prompt use in experimental rats. Following an additional two washes with 0.5 per cent formalin. similar Type I Pseudomonas suspension of 2X IO” microorganisms/ml were prepared for injection into rabbits. When the titre ot the Pseudomonas antiserum level exceeded I : 1000 the rabbits were killed and blood was drawn from the common carotid artery. Samples were centrifuged at 2000~ for ISmin. and supernatant serum was stored at 4°C for later
Using sterile instruments, the lungs, spleen. liver and kidneys of the rats were removed, and quantitative bacterial cultures were performed. All organisms were identified according to information contained in Bergey’s Manual of Determinutive Microbiology (8th ed.). Five-micrometre sections were made of the various tissues, and indirect immunofluorescent staining was accomplished using rabbit Type 1 Pseudomonas antiserum along with sheep’s antiserum labelled with fluorescein isothiocyanate against rabbit IgG. Oil-immersion light microscopy was used for examining the samples for the presence of bacteria. An Olympus fluorescent microscope with HBO 200 light source and darkfield condenser was utilized and photographs were taken.
Burns (1986) Vol. lZ/No. 5
Tissue specimens taken from the liver and the middle region of the small intestine were prepared for routine paraffin embedding, cut to 4um. stained with haematoxylin and eosin, and then coded for histological examination. At the same time, liver specimens were taken for study by electronmicroscopy. The samples were tixed in 3 per cent glutaraldehyde, treated with a 2 per cent osmium tetroxide solution. dehydrated in graded alcohols. then embedded in Epon 812. The sections were stained with uranyl acetate and lead citrate. then examined using a DBX2-IO transmission electronmicroscope.
Evaluation of reticuloendothelial activity
phagocytic
Reticuloendothelial phagocytic function, especially that of the Kupffer cells, was evaluated by measuring the rate of clearance of carbon particles from the blood, using the method of Grun (1976). This experiment was performed using 24 additional rats (six groups of four rats each) treated in exactly the same manner as those of the original groups.
Plasma fibronectin determination Right ventricular blood samples were taken from the animals, and plasma tibronectin levels were determined by the semi-quantitative method reported by Ekindjian et al. (1984).
dicating that intestinal Type 1 Pseudomonas was able to pass through the intestinal mucosal defence barrier and then spread systemically. Two hundred cultures for intestinal bacteria in the above-mentioned viscera were performed. and 43 per cent (86/2(N)) were positive. The positive rate for Type I Pseudomonas was IS.5 per cent (31/200). Corresponding cultures of the control groups yielded an overall positive rate of only 13.6 per cent (27/2(k)), and 2.5 per cent (5/2(N)) for Type I Pseudomonas. These differences were also statistically significant (P4bOS). Blood samples taken from the portal vein, liver, lungs, spleen and kidneys of the burned animals showed the presence of Type I Pseudomonas within 24 h post-burn. indicating that generalized dissemination of intestinal microorganisms had occurred well before the establishment of burn-wound infection. Of I I microorganism species isolated from the organs of the burned animals, 10 were normal endogenous flora of the intestinal tract. These accounted for X3.5 per cent of the positive tindings. Of these. 34.6 per cent were Type I Pseudomonas. 12.0 per cent Alcctli~mrs f~1c~rr1i.s and I I.7 per cent Mima. Polymorpha. Taken collectively. K. ptwutttottitr, Acitwtohct~r cdand Pseudomonas coaceticus var. ‘anitratius’ accounted for 5.X per cent of the total. Strrplrvlococcl~s ~t11trws. the only Gram-positive organism found, accounted for 16.4 per cent of the total.
Statistical analysis Student’s t test and x2 tests were used for calculating the degre of significance between the burn and control groups for both Type I P.wrdottwnas aeruginosa positive culture rates and changes in the number of Kupffer cells. Rank’s test was used to determine the significance of differences in plasma fibronectin levels between the experimental and control groups.
RESULTS Dissemination
of Type 1 Pseudomonas
Both a higher incidence and earlier appearance of Type 1 Pseudomonas were found in the organs of the burned animals in comparison with those of the control groups during the first 48 h following injury. Indirect immunofluorescence staining showed the presence of the Type 1 Pseudomonas in the liver (IO0 per cent), lungs (70 per cent). spleen (50 per cent) and kidneys (40 per cent) of the burned animals at 3 and 6 h post-injury. Some of the burned rats also showed the presence of Type 1 Pseudomonas in the mesenteric lymph nodes. The differences between the burn and control groups were significant (P
Pathogenic changes in the intestinal mucosa Under the light microscope, 60 per cent of the burned animals showed acute stress necrosis of intestinal mucosa at 3 and 6 h post-burn. with the necrotic process developing progressively from the top to the bottom of the intestinal villi. Twelve hours later, there appeared a subepithelial space (Gruenhagen’s space) in the villi (Chiu, 1970). The interstitium of the villi appeared loose. and the central lymphatic vessels showed marked dilatation. Thereafter. oedemn of the intestinal mucosa (especially propria lamina and submucosa lamina) became increasingly marked. with obvious dilatation of the lymphatic ducts. Some degeneration and focal necrosis of epithelial cells of the intestinal mucosa were also seen.
Pathogenic changes in the liver Light microscopy showed significant dilatation and congestion of central veins and sinusoids of the liver during the first I2 h following injury. The number of Kupffer cells present in the sinusoids was relatively small. Twenty-four hours
Ma Li et al.: Dissemination of endogenous microbes after burns
327
/.;,q. I, Kupl’kr ccllz \h(wcd foc;d cytopl;wlc dcgeneration (FCD) (arrow) at 3 h post-burn. The nuclei in cells wcrc compressed hy FCD. x427.5. with the paswge of time and endoplasmic reticular dilatation and heterochromatin m:qination wert’ present. bited
Most
nrcrotic
karyolysis
Kupffer
cells
(Fig. 3). and pyknosi\
k:uyorrhcxis
cxhiand
found.
wt’rc‘ sometimes
Changes in plasma fibronectin levels (Fig. 4) In the burned :mimals. the plasma tibronectln levels were lowest at 3 and 6 h poht-injury. Thereafter. they gradually increased and eventualI> exceedtd that of the control groups. Rank’s test showed the difference between the exprriment;d and control groups to be statistically significant (P
Changes in phagocytic activity of Kupffer cells (Fig. 5) atter
injury.
an obvious
M;I~ ohservcd.
Many
increase Kupffcr
in their cells
number
show4
nuc-
lear degeneration. C cllx were counted under the light nilcroscope. and Student’s I test analysis of the figures indicated that the decrease 111 the number of Kupffcr cells sren at 3 and 6 h poatburn
was statistically
Under showed
the
focal cytoplasmic
3 h post-burn tlilation
bec;une
\,;irious
electron
Kupffer
cells
\~acuolization. cre;lsed nmtrix
and
numt‘rous
In
those
with
density
also
particles
swelling of
Myelin
showed
the figure
in
ccl1 compo-
(/-Y
:III seen.
autoly\osomes
rtzticular
densities than
by
of the nucleus with
other
cells
(FCD)
degencr;tte
mitochondrial
elt‘ctron were
FCD.
Kupffer
Endopl:rsmic
in comprtGon
of
nrcrotic FC‘D, ;lnd
in-
mitochondrial structures
obvious
control. India
as demonstrated
by the administration
of
ink.
DISCUSSION
(P
dcgener:ltion
(Fig. I ).
resulted
cells exhibiting ncnts
siqificant
electronmicroscop~.
During the first 6 h post-burn the phagocytic activity of Kupffer cells in the burned groups was clearly diminished in comparison with that of the
and
increases
Aftrr
severe
wrre
not only
niucos;~ &fence
therm:d able
injury
intestinal
to p;~ss through
barrier.
but were
microbes
the intcstin;ll able to do so at
early time. Similar tindings have recently been reported by Deitch et ;II. (1985). Our data revealed that generalized dissemination of intestinal microbes had occurred well before the ;I very
onset
of burn-wound
infection.
In treirting
burn
much attention should therefore be paid to infection from microbes of the intestinal tract during the verv early post-burn pet-iocl (Ilowerton 1072: jarret. IY78). pkltients.
328
Burns (1986) Vol. 12/No. 5
l/256
4
0
3 /?
6 hhroncctin
12 Hours post-burn concentration
Serious damage to the intestinal mucosa results from severe thermal injury. Since the intestinal lining is an important non-specific mechanical barrier against bacterial invasion. its damage is primarily responsible for the acute invasion of endogenous microbes. The phagocytic activity of Kupffer cells is the main component of the reticuloendothelial defence system. The central role played by Kupffer cells is that of removing both bacterial and nonbacterial particles from the circulation. In healthy individuals endogenous microbial dissemination does not occur, because even though a few bacteria are able to pass through the intestinal barrier, they are promptly phagocytized by Kupffer cells. The post-burn depression of phagocytic activity of Kupffer cells therefore facilitates
24
following
48 hum.
0.
Burned
rats: 0.
the generalized dissemination of intestinal bacteria. In this study all of the pathological changes seen in Kupffer cells indicated that the observed depression of their phagocytic activity was a direct result of their seriously damaged state. Plasma fibronectin appears to act as a nonspecific opsonin for reticuloendothelial system function Ekindjian et al. (1984). Animal studies have shown a close correlation between plasma libronectin levels and RES functional depression, especially when there is Kupffer-cell injury. In this study, it was also seen that the observed sharp drop in plasma fibronectin concentration was concomitant with the various degenerative changes in the Kupffer cells. Acknowledgements
0.20 0.18 siO.16. 0 3 0.14o :; ‘0.12.
The authors gratefully acknowledge the improvements in the English language of the text made by Dr J. W. L. Davies. The skilled typing of Mrs Jean Clark is also acknowledged.
1 mean normal value (0.117OD)
E 10.10. 2 0.08’ 2 9.06. 0.04 1
““‘1 0
3
6 12 24 48 Hours post-burn Fig. S. Lcvcl of Kupfl’cr cell phagocytic activity as dcmonstratcd hy the value of India ink in scqucntial blood samples tahcn over 48 h following thermal injury.
REFERENCES Chiu C. J. (1970) Intestinal mucosal Icsion in low-flow states. Arch. Surg. 101, 47X. Dcitch E. A.. Maejima K. and Berg R. (I9X.S) Et’t’~~t 01 oral antibiotics and bacterial overgrowth on the translocation of the Cl tract microflora in hurncd rats. J. Trmmu 25. 3X5. Ekindjian 0. G., Marien M., Wasermann D. et al. (1984) Plasma fibronectin time course in burned patients: influence of sepsis. J. Trauma 24, 214. Crun M. (1976) Significance of endotoxacmia in cxpcrimcntal “Golactosaminc-hepatitis” in the rat. A C/L/ H~‘I~uI~~-~;~I.sI’.“~III~,~~~/.23. 64.
Ma LI et al.: Dissemination of endogenous microbes after burns
Flowcrton E. E. (lU77) The intestinal tract ;I\ ;I portal 01 cntrv or P~eudonion;ti\ in hurn rat. ./. Trrrruurr 12. 335.
329
.f;lrrct F.
( 1078)
antibiotic
(‘linical
howcl .s/rr
upcricncc
yqxcsaion
with prophylxttc in
hum
paticnth.
Printed in Great Britain
325
Endogenous microbial dissemination following severe burns in rats Ma Li, Xiao Guang-Xia, Burn Center, Southwestern
Wang De Wang and Li Ngao Hospital, Chongqing, Sichuan, China
Summary This study suggests thot dnmagc to the intestinal lining. ;I” important mcchanic;tl harrier against hxtcrial invasion. is the mSn l’xtor leading to the dissemination of endogcnous microhcs. Reduced phagocytic activity of Kupllcr cells and compromised opsonic function ;dso ;~ppc;tr to contrihutc to the process.
INTRODUCTION ONI, of the most
serious complications encountered during the treatment of burn patients is generalized infection. Large wound surface areas serve as portals of entry for a wide variety of infective microorganisms, but might there not be other ways in which translocation of bacteria and generalized infection can occur? This study was undertaken in order to determine whether postburn dissemination of intestinal microbes can occur. and if so. to elucidate the pathological mechanisms involved.
use in indirect dies.
immunofluorescence
staining stu-
Infection and burning of the animals One hundred adult male rats weighing 23(~3OOg were randomly divided into five groups of 20 animals each, the members of each group being killed and examined at either 3. 6, 12, 24 or 48 h after injury. Each group included IO burned rats and IO unburned control rats. Twelve hours before burning all of the rats received the bacterial suspension (0~7ml/l0og body wt) by means of gastric intubation under ether anaesthesia. Thereafter. the animals were given neither food nor water. Half of the animals in each group then received a 30 per cent TBSA full thickness flame burn. All the rats were then killed and examined at various post-burn times, depending on the group to which they belonged.
Preparation of histological samples MATERIALS AND METHODS Preparation of antimicrobial serum Type I P.sc~fomonus aerugino.sa bacteria isolated from infected wounds of burn patients were cultured on blood agar plates at 37°C for 24 h. then washed with normal saline. Bacterial suspensions containing 9X IO’ microorganisms/ml were prepared for prompt use in experimental rats. Following an additional two washes with 0.5 per cent formalin. similar Type I Pseudomonas suspension of 2X IO” microorganisms/ml were prepared for injection into rabbits. When the titre ot the Pseudomonas antiserum level exceeded I : 1000 the rabbits were killed and blood was drawn from the common carotid artery. Samples were centrifuged at 2000~ for ISmin. and supernatant serum was stored at 4°C for later
Using sterile instruments, the lungs, spleen. liver and kidneys of the rats were removed, and quantitative bacterial cultures were performed. All organisms were identified according to information contained in Bergey’s Manual of Determinutive Microbiology (8th ed.). Five-micrometre sections were made of the various tissues, and indirect immunofluorescent staining was accomplished using rabbit Type 1 Pseudomonas antiserum along with sheep’s antiserum labelled with fluorescein isothiocyanate against rabbit IgG. Oil-immersion light microscopy was used for examining the samples for the presence of bacteria. An Olympus fluorescent microscope with HBO 200 light source and darkfield condenser was utilized and photographs were taken.
Burns (1986) Vol. lZ/No. 5
Tissue specimens taken from the liver and the middle region of the small intestine were prepared for routine paraffin embedding, cut to 4um. stained with haematoxylin and eosin, and then coded for histological examination. At the same time, liver specimens were taken for study by electronmicroscopy. The samples were tixed in 3 per cent glutaraldehyde, treated with a 2 per cent osmium tetroxide solution. dehydrated in graded alcohols. then embedded in Epon 812. The sections were stained with uranyl acetate and lead citrate. then examined using a DBX2-IO transmission electronmicroscope.
Evaluation of reticuloendothelial activity
phagocytic
Reticuloendothelial phagocytic function, especially that of the Kupffer cells, was evaluated by measuring the rate of clearance of carbon particles from the blood, using the method of Grun (1976). This experiment was performed using 24 additional rats (six groups of four rats each) treated in exactly the same manner as those of the original groups.
Plasma fibronectin determination Right ventricular blood samples were taken from the animals, and plasma tibronectin levels were determined by the semi-quantitative method reported by Ekindjian et al. (1984).
dicating that intestinal Type 1 Pseudomonas was able to pass through the intestinal mucosal defence barrier and then spread systemically. Two hundred cultures for intestinal bacteria in the above-mentioned viscera were performed. and 43 per cent (86/2(N)) were positive. The positive rate for Type I Pseudomonas was IS.5 per cent (31/200). Corresponding cultures of the control groups yielded an overall positive rate of only 13.6 per cent (27/2(k)), and 2.5 per cent (5/2(N)) for Type I Pseudomonas. These differences were also statistically significant (P4bOS). Blood samples taken from the portal vein, liver, lungs, spleen and kidneys of the burned animals showed the presence of Type I Pseudomonas within 24 h post-burn. indicating that generalized dissemination of intestinal microorganisms had occurred well before the establishment of burn-wound infection. Of I I microorganism species isolated from the organs of the burned animals, 10 were normal endogenous flora of the intestinal tract. These accounted for X3.5 per cent of the positive tindings. Of these. 34.6 per cent were Type I Pseudomonas. 12.0 per cent Alcctli~mrs f~1c~rr1i.s and I I.7 per cent Mima. Polymorpha. Taken collectively. K. ptwutttottitr, Acitwtohct~r cdand Pseudomonas coaceticus var. ‘anitratius’ accounted for 5.X per cent of the total. Strrplrvlococcl~s ~t11trws. the only Gram-positive organism found, accounted for 16.4 per cent of the total.
Statistical analysis Student’s t test and x2 tests were used for calculating the degre of significance between the burn and control groups for both Type I P.wrdottwnas aeruginosa positive culture rates and changes in the number of Kupffer cells. Rank’s test was used to determine the significance of differences in plasma fibronectin levels between the experimental and control groups.
RESULTS Dissemination
of Type 1 Pseudomonas
Both a higher incidence and earlier appearance of Type 1 Pseudomonas were found in the organs of the burned animals in comparison with those of the control groups during the first 48 h following injury. Indirect immunofluorescence staining showed the presence of the Type 1 Pseudomonas in the liver (IO0 per cent), lungs (70 per cent). spleen (50 per cent) and kidneys (40 per cent) of the burned animals at 3 and 6 h post-injury. Some of the burned rats also showed the presence of Type 1 Pseudomonas in the mesenteric lymph nodes. The differences between the burn and control groups were significant (P
Pathogenic changes in the intestinal mucosa Under the light microscope, 60 per cent of the burned animals showed acute stress necrosis of intestinal mucosa at 3 and 6 h post-burn. with the necrotic process developing progressively from the top to the bottom of the intestinal villi. Twelve hours later, there appeared a subepithelial space (Gruenhagen’s space) in the villi (Chiu, 1970). The interstitium of the villi appeared loose. and the central lymphatic vessels showed marked dilatation. Thereafter. oedemn of the intestinal mucosa (especially propria lamina and submucosa lamina) became increasingly marked. with obvious dilatation of the lymphatic ducts. Some degeneration and focal necrosis of epithelial cells of the intestinal mucosa were also seen.
Pathogenic changes in the liver Light microscopy showed significant dilatation and congestion of central veins and sinusoids of the liver during the first I2 h following injury. The number of Kupffer cells present in the sinusoids was relatively small. Twenty-four hours
Ma Li et al.: Dissemination of endogenous microbes after burns
327
/.;,q. I, Kupl’kr ccllz \h(wcd foc;d cytopl;wlc dcgeneration (FCD) (arrow) at 3 h post-burn. The nuclei in cells wcrc compressed hy FCD. x427.5. with the paswge of time and endoplasmic reticular dilatation and heterochromatin m:qination wert’ present. bited
Most
nrcrotic
karyolysis
Kupffer
cells
(Fig. 3). and pyknosi\
k:uyorrhcxis
cxhiand
found.
wt’rc‘ sometimes
Changes in plasma fibronectin levels (Fig. 4) In the burned :mimals. the plasma tibronectln levels were lowest at 3 and 6 h poht-injury. Thereafter. they gradually increased and eventualI> exceedtd that of the control groups. Rank’s test showed the difference between the exprriment;d and control groups to be statistically significant (P
Changes in phagocytic activity of Kupffer cells (Fig. 5) atter
injury.
an obvious
M;I~ ohservcd.
Many
increase Kupffcr
in their cells
number
show4
nuc-
lear degeneration. C cllx were counted under the light nilcroscope. and Student’s I test analysis of the figures indicated that the decrease 111 the number of Kupffcr cells sren at 3 and 6 h poatburn
was statistically
Under showed
the
focal cytoplasmic
3 h post-burn tlilation
bec;une
\,;irious
electron
Kupffer
cells
\~acuolization. cre;lsed nmtrix
and
numt‘rous
In
those
with
density
also
particles
swelling of
Myelin
showed
the figure
in
ccl1 compo-
(/-Y
:III seen.
autoly\osomes
rtzticular
densities than
by
of the nucleus with
other
cells
(FCD)
degencr;tte
mitochondrial
elt‘ctron were
FCD.
Kupffer
Endopl:rsmic
in comprtGon
of
nrcrotic FC‘D, ;lnd
in-
mitochondrial structures
obvious
control. India
as demonstrated
by the administration
of
ink.
DISCUSSION
(P
dcgener:ltion
(Fig. I ).
resulted
cells exhibiting ncnts
siqificant
electronmicroscop~.
During the first 6 h post-burn the phagocytic activity of Kupffer cells in the burned groups was clearly diminished in comparison with that of the
and
increases
Aftrr
severe
wrre
not only
niucos;~ &fence
therm:d able
injury
intestinal
to p;~ss through
barrier.
but were
microbes
the intcstin;ll able to do so at
early time. Similar tindings have recently been reported by Deitch et ;II. (1985). Our data revealed that generalized dissemination of intestinal microbes had occurred well before the ;I very
onset
of burn-wound
infection.
In treirting
burn
much attention should therefore be paid to infection from microbes of the intestinal tract during the verv early post-burn pet-iocl (Ilowerton 1072: jarret. IY78). pkltients.
328
Burns (1986) Vol. 12/No. 5
l/256
4
0
3 /?
6 hhroncctin
12 Hours post-burn concentration
Serious damage to the intestinal mucosa results from severe thermal injury. Since the intestinal lining is an important non-specific mechanical barrier against bacterial invasion. its damage is primarily responsible for the acute invasion of endogenous microbes. The phagocytic activity of Kupffer cells is the main component of the reticuloendothelial defence system. The central role played by Kupffer cells is that of removing both bacterial and nonbacterial particles from the circulation. In healthy individuals endogenous microbial dissemination does not occur, because even though a few bacteria are able to pass through the intestinal barrier, they are promptly phagocytized by Kupffer cells. The post-burn depression of phagocytic activity of Kupffer cells therefore facilitates
24
following
48 hum.
0.
Burned
rats: 0.
the generalized dissemination of intestinal bacteria. In this study all of the pathological changes seen in Kupffer cells indicated that the observed depression of their phagocytic activity was a direct result of their seriously damaged state. Plasma fibronectin appears to act as a nonspecific opsonin for reticuloendothelial system function Ekindjian et al. (1984). Animal studies have shown a close correlation between plasma libronectin levels and RES functional depression, especially when there is Kupffer-cell injury. In this study, it was also seen that the observed sharp drop in plasma fibronectin concentration was concomitant with the various degenerative changes in the Kupffer cells. Acknowledgements
0.20 0.18 siO.16. 0 3 0.14o :; ‘0.12.
The authors gratefully acknowledge the improvements in the English language of the text made by Dr J. W. L. Davies. The skilled typing of Mrs Jean Clark is also acknowledged.
1 mean normal value (0.117OD)
E 10.10. 2 0.08’ 2 9.06. 0.04 1
““‘1 0
3
6 12 24 48 Hours post-burn Fig. S. Lcvcl of Kupfl’cr cell phagocytic activity as dcmonstratcd hy the value of India ink in scqucntial blood samples tahcn over 48 h following thermal injury.
REFERENCES Chiu C. J. (1970) Intestinal mucosal Icsion in low-flow states. Arch. Surg. 101, 47X. Dcitch E. A.. Maejima K. and Berg R. (I9X.S) Et’t’~~t 01 oral antibiotics and bacterial overgrowth on the translocation of the Cl tract microflora in hurncd rats. J. Trmmu 25. 3X5. Ekindjian 0. G., Marien M., Wasermann D. et al. (1984) Plasma fibronectin time course in burned patients: influence of sepsis. J. Trauma 24, 214. Crun M. (1976) Significance of endotoxacmia in cxpcrimcntal “Golactosaminc-hepatitis” in the rat. A C/L/ H~‘I~uI~~-~;~I.sI’.“~III~,~~~/.23. 64.
Ma LI et al.: Dissemination of endogenous microbes after burns
Flowcrton E. E. (lU77) The intestinal tract ;I\ ;I portal 01 cntrv or P~eudonion;ti\ in hurn rat. ./. Trrrruurr 12. 335.
329
.f;lrrct F.
( 1078)
antibiotic
(‘linical
howcl .s/rr
upcricncc
yqxcsaion
with prophylxttc in
hum
paticnth.