• The Korean Journal of Physiology
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• v.15 no.1
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• pp.27-36
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• 1981

Relatively little has been done on the metabolic changes of the lung produced by the excessive alcohol ingestion to the point of the acute alcohol intoxication. In the present study, an effort was made to clarify the possible changes of the pulmonary surfactant system by the acute alcohol ingestion. The dynamic pulmonary compliance and the levels of protein and inorganic phosphorus (Pi) of both lung lavage and extract were chosen as the parameters of the pulmonary surfactant activities. The albino rats of both sexes were used, and 1.5 ml of 50% ethanol per 100 g body weight was given by oral intubation, and the experiment was performed at 1, 3, 6, 12, and 24 hours after the alcohol ingestion. The rat was sacrificed by cutting the carotid arteries, and blood sample for the determination of hematocrit(Hct) and the blood alcohol concentration was obtained. Both lungs were completely removed without dammage to the lung tissue, and the pulmonary compliance was measured by the changes of pressure-volume(P-V) curves by inflating or deflating the lung with air. Immediately after the P-V curves were recorded, the lung lavage was obtained by washing the lobes with 15ml of isotonic saline 3 times with a syringe. Next, total lungs were homogenized and filtered to obtain the lung extract. The protein and Pi levels were measured using the lung lavage and extract as the samples, and the lung/body weight ratio(L/B ratio) was also calculated. The results thus obtained were compared with the normal values and summarized as follows. The blood alcohol concentration reached the highest level of $0.71{\pm}0.02\;g\;%$ at 1 hr and gradually decreased until 24 hrs$(0.36{\pm}0.02\;g%)$ after the alcohol ingestion, but all the experimental groups showed significant increase comparing with the normal. The highest Hct value was obtained at 1hr$(64.86{\pm}2.45%)$ and significantly elevated value was continued throughout the experiment. The L/B ratio was significantly lowered from 3hrs until 24hrs after the alcohol ingestion but from 6 th hr on, a generally elevated value was observed with a significant value at 12 hrs and gradual recovery to the normal value at 24 hrs after the alcohol ingestion. The pulmonary compliance at inflation and deflation did not change appreciablly from the normal until 3 hrs after the alcohol ingestion but from 6 th hr on, a generally elevated value was observed with a significant value at 12 hrs and gradual recovery to the normal value at 24 hrs after the alcohol ingestion. The protein level of the lung lavage stowed a significantly increased value of $12.36{\pm}0.35\;mg/gm(3rd hr)$, $12.70{\pm}0.74\;mg/gm(12 th hr)$, and $12.65{\pm}0.88\;mg/gm(24 th hr)$, respectively, comparing with the normal value of $10.65{\pm}0.62\;mg/gm$, and the Pi level also showed a similar tendency of significant increase at 12th hr $(7.65{\pm}0.63\;{\mu}mol/gm)$ and 24 th hr$(6.70{\pm}0.36\;{\mu}mol/gm)$ comparing with the normal value of $5.32{\pm}0.20\;{\mu}mol/gm$. The protein level of the lung extract in the alcohol group was generally similar to the normal value with a slight decrease at 1st and 3 rd hr, tut the Pi level of the lung extract was generally increased in the alcohol group, and a significant increase was observed at 6 th hr$(17.77{\pm}1.54\;{\mu}mol/gm)$, 12 th hr$(13.92{\pm}0.78\;{\mu}mol/gm)$ and 24 th hr$(14.57{\pm}0.53\;{\mu}mol/gm)$ of the alcohol ingestion comparing with the normal value of $10.34{\pm}0.37\;{\mu}mol/gm$. From the above, it may be concluded that the acute alcohol intoxication produces the metabolic changes of the lungs by the increased surfactant activities and elevated pulmonary compliance.

• Journal of Chest Surgery
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• v.39 no.12 s.269
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• pp.879-890
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• 2006

Background: The dysfunction of multiple organs is found to be caused by reactive oxygen species as a major modulator of microvascular injury after hemorrhagic shock. Hemorrhagic shock, one of many causes inducing acute lung injury, is associated with increase in alveolocapillary permeability and characterized by edema, neutrophil infiltration, and hemorrhage in the interstitial and alveolar space. Aggressive and rapid fluid resuscitation potentially might increased the risk of pulmonary dysfunction by the interstitial edema. Therefore, in order to improve the pulmonary dysfunction induced by hemorrhagic shock, the present study was attempted to investigate how to reduce the inflammatory responses and edema in lung. Material and Method: Male Sprague-Dawley rats, weight 300 to 350 gm were anesthetized with ketamine(7 mg/kg) intramuscular Hemorrhagic Shock(HS) was induced by withdrawal of 3 mL/100 g over 10 min. through right jugular vein. Mean arterial pressure was then maintained at $35{\sim}40$ mmHg by further blood withdrawal. At 60 min. after HS, the shed blood and Ringer's solution or 5% albumin was infused to restore mean carotid arterial pressure over 80 mmHg. Rats were divided into three groups according to rectal temperature level($37^{\circ}C$[normothermia] vs $33^{\circ}C$[mild hypothermia]) and resuscitation fluid(lactate Ringer's solution vs 5% albumin solution). Group I consisted of rats with the normothermia and lactate Ringer's solution infusion. Group II consisted of rats with the systemic hypothermia and lactate Ringer's solution infusion. Group III consisted of rats with the systemic hypothermia and 5% albumin solution infusion. Hemodynamic parameters(heart rate, mean carotid arterial pressure), metabolism, and pulmonary tissue damage were observed for 4 hours. Result: In all experimental groups including 6 rats in group I, totally 26 rats were alive in 3rd stage. However, bleeding volume of group I in first stage was $3.2{\pm}0.5$ mL/100 g less than those of group II($3.9{\pm}0.8$ mL/100 g) and group III($4.1{\pm}0.7$ mL/100 g). Fluid volume infused in 2nd stage was $28.6{\pm}6.0$ mL(group I), $20.6{\pm}4.0$ mL(group II) and $14.7{\pm}2.7$ mL(group III), retrospectively in which there was statistically a significance between all groups(p<0.05). Plasma potassium level was markedly elevated in comparison with other groups(II and III), whereas glucose level was obviously reduced in 2nd stage of group I. Level of interleukine-8 in group I was obviously higher than that of group II or III(p<0.05). They were $1.834{\pm}437$ pg/mL(group I), $1,006{\pm}532$ pg/mL(group II), and $764{\pm}302$ pg/mL(group III), retrospectively. In histologic score, the score of group III($1.6{\pm}0.6$) was significantly lower than that of group I($2.8{\pm}1.2$)(p<0.05). Conclusion: In pressure-controlled hemorrhagic shock model, it is suggested that hypothermia might inhibit the direct damage of ischemic tissue through reduction of basic metabolic rate in shock state compared to normothermia. It seems that hypothermia should be benefit to recovery pulmonary function by reducing replaced fluid volume, inhibiting anti-inflammatory agent(IL-8) and leukocyte infiltration in state of ischemia-reperfusion injury. However, if is considered that other changes in pulmonary damage and inflammatory responses might induce by not only kinds of fluid solutions but also hypothermia, and that the detailed evaluation should be study.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.215-228
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• 1999

Background: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology often involving the lungs and intrathoracic lymph nodes. The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. But, the mechanisms causing the variable clinical outcomes or any single parameter to predict the prognosis was not known. In sarcoidosis, the number and the activity of CD4 + lymphocytes are significantly increased at the loci of disease and their oligoclonality suggests that the CD4 + lymphocytes hyperreactivity may be caused by persistent antigenic stimulus. Recently, it has been known that CD4+ lymphocytes can be subdivided into 2 distinct population(Th1 and Th2) defined by the spectrum of cytokines produced by these cells. Th1 cells promote cellular immunity associated with delayed type hypersensitivity reactions by generating IL-2 and IFN-$\gamma$. Th2 cells playa role in allergic responses and immediate hypersensitivity reactions by secreting IL-4, IL-5, and IL-10. CD4+ lymphocytes in pulmonary sarcoidosis were reported to be mainly Th1 cells. IL-12 has been known to play an important role in differentiation of undifferentiated naive T cells to Th1 cells. And, Moller et al. observed increased IL-12 in bronchoalveolar lavage fluid(BALF) in patients with sarcoidosis. So it is possible that the elevated level of IL-12 is necessary for the continuous progression of the disease in active sarcoidosis. This study was performed to test the assumption that IL-12 can be a marker of active pulmonary sarcoidosis. Methods: We measured the concentration of IL-12 in BALF and in conditioned medium of alveolar macrophage(AM) using ELISA(enzyme-linked immunosorbent assay) method in 26 patients with pulmonary sarcoidosis(10 males, 16 females, mean age: $39.8{\pm}2.1$ years) and 11 normal control. Clinically, 14 patients had active sarcoidosis and 12 patients had inactive. Results: Total cells counts, percentage and number of lymhocytes, number of AM and CD4/CD8 lymphocyte ratio in BALF were significantly higher in patients with sarcoidosis than in control group. But none of these parameters could differentiate active sarcoidosis from inactive disease. The concentration of IL-12 in BALF was significantly increased in sarcoidosis patients ($49.3{\pm}9.2$ pg/ml) than in normal control ($2.5{\pm}0.4$ pg/ml) (p<0.001). Moreover it was significantly higher in patients with active sarcoidosis ($70.3{\pm}14.8$ pg/ml) than in inactive disease ($24.8{\pm}3.l$ pg/ml) (p=0.001). Also, the concentration of IL-12 in BALF showed significant correlation with the percentage of AM(p<0.001), percentage(p<0.001) and number of lymphocyte(p<0.001) in BALF, suggesting the close relationship between the level of IL-12 in BALF and the inflammatory cell infiltration in the lungs. Furthermore, we found a significant correlation between the level of IL-12 and the concentration of soluble ICAM-1 : in serum(p<0.001) and BALF (p=0.001), and also between IL-12 level and ICAM-1 expression of AM(p<0.001). The AM from patients with pulmonary sarcoidosis secreted significantly larger amount of IL-12 ($206.2{\pm}61.9$ pg/ml) than those of control ($68.3{\pm}43.7$ pg/ml) (p<0.008), but, there was no difference between inactive and active disease group. Conclusion : Our data suggest that the BALF IL-12 level can be used as a marker of the activity of pulmonary sarcoidosis.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.5-19
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• 1998

Introduction: Direct histologic and bacteriologic examination of a representative specimen of lung tissue is the only certain method of providing an accurate diagnosis in various pulmonary diseases including diffuse pulmonary diseases. The purpose of national survey was to define the indication, incidence, effectiveness, safety and complication of open and thoracoscopic lung biopsy in korea. Methods: A multicenter registry of 37 university or general hospitals equipped more than 400 patient's bed were retrospectively collected and analyzed for 3 years from the January 1994 to December 1996 using the same registry protocol. Results: 1) There were 511 cases from the 37 hospitals during 3 years. The mean age was 50.2 years(${\pm}15.1$ years) and men was more prevalent than women(54.9% vs 45.9%). 2) The open lung biopsy was performed in 313 cases(62%) and thoracoscopic lung biopsy was performed in 192 cases(38%). The incidence of lung biopsy was more higher in diffuse lung disease(305 cases, 59.7%) than in localized lung disease(206 cases, 40.3%) 3) The duration after abnormalities was found in chest X-ray until lung biopsy was 82.4 days(open lung biopsy: 72.8 days, thoracoscopic lung biopsy: 99.4 days). The bronchoscopy was performed in 272 cases(53.2%), bronchoalveolar lavage was performed in 123 cases(24.1%) and percutaneous lung biopsy was performed in 72 cases(14.1%) before open or thoracoscopic lung biopsy. 4) There were 230 cases(45.0%) of interstitial lung disease, 133 cases(26.0%) of thoracic malignancies, 118 cases(23.1%) of infectious lung disease including tuberculosis and 30 cases (5.9 %) of other lung diseases including congenital anomalies. No significant differences were noted in diagnostic rate and disease characteristics between open lung biopsy and thoracoscopic lung biopsy. 5) The final diagnosis through an open or thoracoscopic lung biopsy was as same as the presumptive diagnosis before the biopsy in 302 cases(59.2%). The identical diagnostic rate was 66.5% in interstitial lung diseases, 58.7% in thoracic malignancies, 32.7% in lung infections, 55.1 % in pulmonary tuberculosis, 62.5% in other lung diseases including congenital anomalies. 6) One days after lung biopsy, $PaCO_2$ was increased from the prebiopsy level of $38.9{\pm}5.8mmHg$ to the $40.2{\pm}7.1mmHg$(P<0.05) and $PaO_2/FiO_2$ was decreased from the prebiopsy level of $380.3{\pm}109.3mmHg$ to the $339.2{\pm}138.2mmHg$(P=0.01). 7) There was a 10.1 % of complication after lung biopsy. The complication rate in open lung biopsy was much higher than in thoracoscopic lung biopsy(12.4% vs 5.8%, P<0.05). The incidence of complication was pneumothorax(23 cases, 4.6%), hemothorax(7 cases, 1.4%), death(6 cases, 1.2%) and others(15 cases, 2.9%). 8) The 5 cases of death due to lung biopsy were associated with open lung biopsy and one fatal case did not describe the method of lung biopsy. The underlying disease was 3 cases of thoracic malignancies(2 cases of bronchoalveolar cell cancer and one malignant mesothelioma), 2 cases of metastatic lung cancer, and one interstitial lung disease. The duration between open lung biopsy and death was $15.5{\pm}9.9$ days. 9) Despite the lung biopsy, 19 cases (3.7%) could not diagnosed. These findings were caused by biopsy was taken other than target lesion(5 cases), too small size to interpretate(3 cases), pathologic inability(11 cases). 10) The contribution of open or thoracoscopic lung biopsy to the final diagnosis was defininitely helpful(334 cases, 66.5%), moderately helpful(140 cases, 27.9%), not helpful or impossible to judge(28 cases, 5.6%). Overall, open or thoracoscopic lung biopsy were helpful to diagnose the lung lesion in 94.4 % of total cases. Conclusions: The open or thoracoscopic lung biopsy were relatively safe and reliable diagnostic method of lung lesion which could not diagnosed by other diagnostic approaches such as bronchoscopy. We recommend the thoracoscopic lung biopsy when the patients were in critical condition because the thoracoscopic biopsy was more safe and have equal diagnostic results compared with the open lung biopsy.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1236-1251
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• 1998

Background : TNF-$\alpha$ appears to be a central mediator of the host response to sepsis. While TNF-$\alpha$ is mainly considered a proinflammatory cytokine, it can also act as a direct cytotoxic cytokine. However, there are not so many studies about the relationship bet ween TNF-$\alpha$ level and lung injury severity in ALI, particularly regarding the case of ALI caused by direct lung injury such as diffuse pulmonary infection. Recently, a natural defense mechanism, known as the stress response or the heat shock response, has been reported in cellular or tissue injury reaction. There are a number of reports examining the protective role of pre-induced heat stress proteins on subsequent LPS-induced TNF-$\alpha$ release from monocyte or macrophage and also on subsequent LPS-induced ALI in animals. However it is not well established whether the stress protein synthesis such as HSP can be induced from rat alveolar macrophages by in vitro or in vivo LPS stimulation. Methods : We measured the level of TNF-$\alpha$, the percentage of inflammatory cells in bronchoalveolar lavage fluid, protein synthesis in alveolar macrophages isolated from rats at 1, 2, 3, 4, 6, 12, and 24 hours after intratracheal LPS instillation. We performed histologic examination and also obtained histologic lung injury index score in lungs from other rats at 1, 2, 3, 4, 6, 12, 24 h after intratracheal LPS instillation. Isolated non-stimulated macrophages were incubated for 2 h with different concentration of LPS (0, 1, 10, 100 ng/ml, 1, or 10 ${\mu}g/ml$). Other non-stimulated macrophages were exposed at $43^{\circ}C$ for 15 min, then returned to at $37^{\circ}C$ in 5% CO2-95% for 1 hour, and then incubated for 2 h with LPS (0, 1, 10, 100ng/ml, 1, or 10 ${\mu}g/ml$). Results : TNF-$\alpha$ levels began to increase significantly at 1 h, reached a peak at 3 h (P<0.0001), began to decrease at 6 h, and returned to control level at 12 h after LPS instillation. The percentage of inflammatory cells (neutrophils and alveolar macrophages) began to change significantly at 2 h, reached a peak at 6 h, began to recover but still showed significant change at 12 h, and showed insignificant change at 24 h after LPS instillation compared with the normal control. After LPS instillation, the score of histologic lung injury index reached a maximum value at 6 h and remained steady for 24 hours. 35 kDa protein band was newly synthesized in alveolar macrophage from 1 hour on for 24 hours after LPS instillation. Inducible heat stress protein 72 was not found in any alveolar macrophages obtained from rats after LPS instillation. TNF-$\alpha$ levels in supernatants of LPS-stimulated macro phages were significantly higher than those of non-stimulated macrophages(p<0.05). Following LPS stimulation, TNF-$\alpha$ levels in supernatants were significantly lower after heat treatment than in those without heat treatment (p<0.05). The inducible heat stress protein 72 was not found at any concentrations of LPS stimulation. Whereas the 35 kDa protein band was exclusively found at dose of LPS of 10 ${\mu}g/ml$. Conclusion : TNF-$\alpha$ has a direct or indirect close relationship with lung injury severity in acute lung injury or acute respiratory distress syndrome. In vivo and in vitro LPS stimulation dose not induce heat stress protein 72 in alveolar macrophages. It is likely that 35 kDa protein, synthesized by alveolar macrophage after LPS instillation, does not have a defense role in acute lung injury.

• Tuberculosis and Respiratory Diseases
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• v.39 no.6
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• pp.453-473
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• 1992

Background: National survey was performed to estimate the incidence of sarcoidosis in Korea. The clinical data of confirmed cases were analysed for the practice of primary care physicians and pulmonary specialists. Methods: The period of study was from January 1991 to December 1992. Data were retrospectively collected by correspondence with physicians in departments of internal medicine, dermatology, ophthalmology and neurology of the hospitals having more than 100 beds using returning postcards. In confirmed and suspicious cases of sardoidosis, case record chart for clinical and laboratory findings were obtained in detail. Results: 1) Postcards were sent to 523 departments in 213 hospitals. Internal medicine composed 41%, dermatology 20%, ophthalmology 20% and neurology 19%. 2) Postcards were returned from 241 departments (replying rates was 48%). 3) There were 113 confirmed cases from 50 departments and 10 cases. The cases were composed from internal medicine (81%), dermatology (13%), ophthalmology (3%) and neurology (3%). 78 confirmed cases were analysed, which were composed from department of internal medicine (92%), dermatology (5%), and neurology (3%). 4) The time span for analysed cases was 1980 to 1992. one case was analysed in 1980 and the number gradually increased to 18 cases in 1991. 5) The majority of patients (84.4%) were in the age group of 20 to 49 years. 6) The ratio of male to female was 1 : 1.5. 7) The most common chief complains were respiratory symptoms, dermatologic symptoms, generalized discomforts, visual changes, arthralgia, abdominal pains, and swallowing difficulties in order. 16% of the patients were asymptomatic. 8) Mean duration between symptom onset and diagnosis was 2 months. 9) The most common symptoms were respiratory, general, dermatologic, ophthalmologic, neurologic and cardiac origin in order. 10) Hemoglobin, hematocrits and platelet were in normal range. 58% of the patients had lymphopenia measuring less than 30% of white cell count. The ratio of CD4 to CD8 lymphocytes was $1.73{\pm}1.16$ with range of 0.43 to 4.62. ESR was elevated in 43% of the cases. 11) Blood chemistry was normal in most cases. Serum angiotensin converting enzyme (S-ACE) was $66.8{\pm}58.6\;U/L$ with the range of 8.79 to 265 U /L. Proteinuria of more than 150 mg was found in 42. 9% of the patients. 12) Serum IgG was elevated in 43.5%, IgA in 45.5%, IgM in 59.1% and IgE in 46.7%. The levels of complement C3 and C4 were in the normal range. Anti-nuclear antibody was detected in 11% of the cases. Kweim test was performed in 3 cases, and in all cases the result was positive. 13) FVC was decreased in 17.3%, FEV1 in 11.5%, FEV1/FVC in 10%, TLC in 15.2%, and DLco in 64.7%. 14) PaO2 was decreased below 90 mmHg in 48.6% and PaCO2 was increased above 45 mmHg in 5.7%. 15) The percentage of macrophages in BAL fluid was $51.4{\pm}19.2%$, lymphocytes $44.4{\pm}21.1%$, and the ratio of CD4 to CD8 lymphocytes was $3.41{\pm}2.07$. 16) There was no difference in laboratory findings between male and female. 17) Hilar enlargement on chest PA was present in 87.9% (bilaterally in 78.8% and unilaterally in 9.1%). 18) According to Siltzbach's classification, stage 0 was 5%, stage 158.3%, stage 228.3%, and stage 38.3%. 19) Hilart enlargement on chest CT was present in 92.6% (bilaterally 76.4% and unilaterally in 16.2%). 20) HRCT was done in 16 cases. The most common findings were nodules, interlobular thickening, focal patchy infiltrations in order. Two cases was normal finding. 21) Other radiologic examinations showed bone change in one case and splenomegaly in two cases. 22) Gallium scan was done in 12 cases. Radioactivity was increased in hilar and mediastinal lymph nodes in 8 cases and in parenchyme in 2 cases. 23) The pathologic diagnosis was commonly performed by transbrochial lung biopsy (TBLB, 47.3%), skin and mediastinal lymph nodes biopsy (34.5%), peripheral lymph nodes biopsy (23.6%), open lung biopsy (18.2%) and bronchial biopsy in order. 24) The most common findings in pathology were non·caseating granuloma (100%), multi-nucleated giant cell (47.3%), hyalinized acellular scar (34.5%), reticulin fibrin network (20%), inclusion body (10.9%), necrosis (9.1%), and lymphangitic distribution of granuloma (1.8%) in order. Conclusion: Clinical, laboratory, radiologic and pathologic findings were summarized. This collected data will assist in finding a test for detection and staging of sarcoidosis in Korea in near future.

• The Korean Journal of Nuclear Medicine
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• v.4 no.1
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• pp.19-26
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• 1970

1. Sixteen normal healthy subjects free from occult blood in the stool were selected and administered with their $^{51}Cr$ labeled own blood via duodenal tube and the recovery rate of radioactivity in feces and urine was measured. The average fecal recovery rate was 90.7 per cent ($85.7{\sim}97.7%$) of the administered radioactivity, and the average urinary excretion rate was 0.8 per cent ($0.5{\sim}1.5%$) 2. There was a close correlation between the amount of blood administered and the recovery rate from the feces; the more the blood administered, the higher the recovery rate was. It was also found that the administration of the tagged blood in the amount exceeding 15ml was suitable for measuring the radioactivity in the stools. 3. In five normal healthy subjects whose circulating erythrocytes had been tagged with $^{51}Cr$, there was little fecal excretion of radioactivity (average 0.9 ml of blood per day). This excretion is not related to hemorrhage and the main route of excretion of such an negligible radioactivity was postulated as gastric juice and bile. 4. A comparison of the radioactivity in the blood and feces of the patients with $^{51}Cr$ labeled erythrocytes seems to be a valid way of estimating intestinal blood loss.