A new experimental trial using repeated heating every 24 hours for local hyperthermic therapy with bleomycin in vivo.

This report presents the effect of repeated heating every 24 hrs using bleomycin (BLM) which, although seemingly contrary to the usual agreement that hyperthermia should be carried out with a long interval due to thermotolerance, holds many possibilities. FM3A cells on the foot pad of C3H mouse were immersed in a heated water bath at 43 and 44 degrees C for 30 min. The effect of repeated heating was appreciated by an improved growth curve and 50 day survival compared to mice which received heating twice with a 96-hr interval. Repeated heating every 24 hrs 5 times with BLM suppressed tumor growth significantly as compared to heating twice with a 96-hr interval without BLM. The longest survival time was obtained by the repeated heating with BLM among all protocols. There is therefore a good possibility that more effective results could be obtained clinically by repeated heating over a short period.     

Experimental studies on thermotolerance in hyperthermia treatment of cancer

Thermotolerance was investigated in hyperthermia using FM3A cells in vitro and in vivo. FM3A cells were heated at 42.0 degrees C, 43.0 degrees C and 44.0 degrees C and the survival rate of the cells was decreased in this order. In in vitro experiments, thermotolerance induced by heating at 43.0 degrees C for 30 min reached at maximum, when the heating interval was 12 hr and thermotolerance induced by heating at 44.0 degrees C for 30 min reached at maximum, when the heating interval was 12 to 24 hr. In in vivo experiments, thermotolerance induced by heating at 42.0 degrees C, 43.0 degrees C and 44.0 degrees C continued for 48 hr after initial heating and disappeared after 96 hr. In the repeated hyperthermia experiments, 7 times with 24 hr interval heating or 4 times with 48 hr interval heating did not show the significant inhibition of tumor growth as compared with the control group at 42.0 degrees C, 43.0 degrees C and 44.0 degrees C. However, twice with 96 hr interval heating indicated the significant inhibition of tumor growth at 42.0 degrees C, 43.0 degrees C and 44.0 degrees C. From these results it is suggested that hyperthermia treatment should be repeated after the disappearance of thermotolerance.     

Combined effects of local hyperthermia, bleomycin, and x-ray on Ehrlich ascites tumor in mice

The combined effects of local hyperthermia at 42.5 degrees C for 30 minutes (HTM), 1/10 LD50 Bleomycin iv(BLM) and 200 rad-irradiation (200R) were studied in DDD strain male mice with Ehrlich ascites tumor. The objective was to acquire data on the optimum regimen for a combined administration of these 3 modalities. The treatments were carried out 10 days after the inoculation of 2 X 10(6) of the cells into the right hind-limb. HTM was applied by water bath heating. Concomitant application of the 3 modalities led to the best effect with a 80% complete regression. A single modality produced no significant effect and a 30-50% regression occurred when 2 modalities were combined. To assess the influence of timing and sequence, HTM was applied at 1,2,4 and 6 hours before, after or simultaneously with the combination of BLM and 200R. A significant effect was obtained in case of simultaneous application of the 3 modalities and the effectiveness of HTM remained as long as the time interval between HTM and BLM plus 200R was 2 hours. This enhancement disappeared in case of 4 hour intervals.     

Chemosensitivity testing on human bladder cancer cell lines, using MTT-assay

Sensitivity of human transitional cancer cells to anticancer agents was evaluated utilizing cultured cell lines. T-24, MGH-U1 and KU-1. Simultaneously, chemosensitivity tests combined with 42 degrees C hyperthermia were performed. Cells inoculated in 96-well multiplates for 48 hours, were exposed to graded concentrations of doxorubicin (DOX), mitomycin C (MMC), bleomycin (BLM), peplomycin (PEP), cis-diamminedichloroplatinum (II) (CDDP) for 2 to 48 hours. After additional culture for 48 hours, viable cell numbers were estimated by the dye exclusion assay (DEA) and tetrazolium-based colorimetric assay (MTT-assay). In 2-hour exposure, most of anti-cancer agents did not significantly suppress the growth of the cell lines. Only DOX suppressed the cell growth. In 6-hour and 48-hour exposure, DOX, MMC and CDDP showed significant growth inhibitory effect on the transitional cancer cell lines. The effect of BLM and PEP was insufficient. The hyperthermia of 42 degrees C enhanced the growth inhibitory effect of MMC and CDDP, but did not influence the effect of DOX. In comparison of DEA and MTT-assay, viable cell numbers measured by DEA well correlated with the optical density in MTT-assay. Since MTT-assay is a semiautomated, rapid and inexpensive assay with good reproducibility, it can be a useful substitute for DEA in chemosensitivity testing of cancer cells.     

结肠运输试验的价值、诊断标准及临床应用

目的：探讨结肠运输试验的准确性及其临床应用价值。方法：连续3 d摄入不同形状的不透X线标记物随踪摄腹部平片5 d，回顾性分析100例受试者的110次检查。结果：3种标记物运输结果基本相符者98例次(89．1％)，明显不符者12例次(10．9％)；46例运输正常的138枚胶囊中9枚胶囊的标记物直至96 h方基本排空；72 h和96 h不同标记物剩余数相差10粒以上者分别为19(1 7．3％)和12(10．9％)例次；重复检查的10例中4例的2次运输结果不符。结论：结肠功能的不稳定性决定了运输试验具有一定程度的偶然性和不可靠性。3枚胶囊5片法能最大限度地避免检查的失误，在决定结肠慢运输病人切除结肠前应采用本法复查。     

不同热剂量局部热疗对小鼠黑色素瘤的疗效及其抗肿瘤免疫激发作用的比较研究

目的探讨既能有效杀伤肿瘤细胞又能最大限度激发抗肿瘤免疫的最适热剂量。方法体外实验采用MTT法检测不同热剂量（43℃30min和55℃10min）单次热疗及间隔24、48、72h的两次热疗对肿瘤细胞的杀伤作用。体内实验采用电热光聚焦加热灯对荷瘤小鼠移植瘤进行43℃及55℃局部热疗,观察不同热剂量对荷瘤小鼠的肿瘤生长、T细胞亚群及白细胞介素2（IL-2）的影响。结果体外实验显示热处理各组细胞存活率均明显降低,尤以55℃热疗最为显著。除了间隔72h的43℃两次热疗组外,重复热疗后细胞存活率均明显降低（P=0.000）。体内实验显示,肿瘤局部常规温度热疗（43℃30min）不能有效抑制荷瘤小鼠移植瘤生长,而高热热疗（55℃10min）在持续24天的观察中,与对照组和43℃热疗组相比肿瘤生长被明显抑制（P〈0.05）,且外周血CD4＋T淋巴亚群比例和CD4＋/CD8＋比值以及IL-2水平均明显升高（P〈0.05）。结论高温局部热疗较常规温度热疗更能有效地抑制肿瘤生长,并激发更强的抗肿瘤免疫。     

Low level 809-nm diode laser-induced in vitro stimulation of the proliferation of human gingival fibroblasts

BACKGROUND AND OBJECTIVE: The authors investigated the effects of low level laser irradiation on the proliferation rate of human gingival fibroblasts (HGF) in vitro. STUDY DESIGN/MATERIALS AND METHODS: HGF were obtained from gingival connective tissue explants and cultured under standard conditions. 110 cell cultures in their logarithmic growth phase were spread on 96-well tissue culture plates and were irradiated at energy fluences of 1.96-7.84 J/cm(2). Another 110 cultures served as control. An 809-nm semiconductor laser operated at a power output of 10 mW in the cw-mode was used. The time of exposure varied between 75 and 300 seconds. Laser treatment was performed alternatively once, twice, and three times at a 24-hour interval. After lasing, incubation was continued for 24 hours. The proliferation rate was determined by means of fluorescence activity of a redox indicator added to the cell culture. Proliferation was determined 24, 48, and 72 hours after irradiation and expressed in relative fluorescence units (RFU). RESULTS: The irradiated cells revealed a considerably higher proliferation activity. The differences were highly significant 24 hour after irradiation (Mann-Whitney U-test, P < 0.05) but decreased in an energy-dependent manner after 48 and 72 hour after irradiation. CONCLUSIONS: A cellular effect of the soft laser irradiation on HGF is evident. Its duration, however, seems to be limited. These findings might be clinically relevant, indicating that repeated treatments are necessary to achieve a positive laser effect in clinical applications.     

Experimental study on tumor growth in the regenerating liver

The purpose of this study was to investigate the effect of liver regeneration on the growth of liver tumor. VX2 carcinoma was transplanted in the liver of New Zealand white rabbits, and 40% partial hepatectomy was performed. The following results were obtained. 1. After 40% partial hepatectomy VX2 carcinoma was transplanted in the remaining liver. Two weeks later, the tumor volume was larger in partially hepatectomized than in shamoperated rabbits (p less than 0.01). 2. When 40% hepatectomy of rabbits which carrying VX2 carcinoma transplanted 2 weeks previously was performed, the mitotic index of the tumor at 24 to 36 hours was significantly higher in hepatectomized than in sham-operated rabbits (p less than 0.02). At 24, 36, 48 hours after partial hepatectomy, the mitotic index of the hepatocytes of the hepatectomized group was significantly higher than that of sham-operated group (24 hrs.: p less than 0.005, 36 hrs.: p less than 0.01, 48 hrs.: p less than 0.005). 3. At 36 hours after partial hepatectomy there was a significant increase of DNA synthesis in tumor cells as compared with that in sham-operated controls (p less than 0.05). These data indicate that liver regeneration enhances the tumor growth in regenerating liver.     

Tissue culture studies on compensatory testicular hypertrophy of the young rabbit after hemicastration

The regulation of compensatory testicular growth after hemicastration using prepubertal rabbits (less than 1000 g) was analyzed by weight increase of the remaining testis. At the 4th week postoperatively, the testis of hemicastrated rabbits weighed about 0.453 mg/g (testis weight/body weight) while the testis of sham operated rabbits weighed about 0.258 mg/g (testis weight/body weight). Thus, the testis of hemicastrated young rabbits developed compensatory growth up to about twice the size of control rabbit testis. This was further confirmed by the histological analysis of testes, in which the number of seminiferous tubules of hemicastrated rabbits was doubled as compared with the sham operated animal. The rabbit testicular cells obtained from the above operated testis could be cultured in monolayer form. These cultured monolayered cells were synchronized by culture in serum-free minimum essential medium (MEM) for 24 hrs. These primary rabbit testicular cells synthesized more DNA and RNA when cultured in a medium that contained hemicastrated rabbit serum, than in that containing normal serum. Stimulation of 3H-thymidine and 3H-uridine incorporation reached the maximum on the 4th day postoperation and thereafter DNA synthesis decreased rapidly whereas RNA synthesis decreased gradually. However, these cells cultured in MEM containing sham operated serum showed no significant increase in 3H-thymidine or 3H-uridine incorporation. Thus, the hemicastrated serum must contain a testis growth stimulating factor(s). Primary monkey testicular cells and primary rat testicular cells were treated with hemicastrated rabbits serum. The testicular cells of these animal species were insensitive to growth stimulation by the hemicastrated serum, which suggests that the testicular growth stimulation is species specific.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypothermic preservation of the rat liver assessed by orthotopic transplantation. II. Evaluation of citrate solutions

Rat livers were flushed with isotonic citrate solution (IC), hypertonic citrate solution (HC), or Collins' solution (C2), and were stored at 0 degree C for 8-16 hr. Following 8-hr preservation, the number of animals surviving for one month was greatest with IC grafts (6/8) and least with C2 grafts (2/7). There was no significant difference between the two citrate groups. Following 12-hr preservation, the IC group was superior to the HC group (3/6 vs. 1/6). Following 16-hr preservation, all four animals in each citrate group died within 24 hr. The ability of livers to produce bile was greater in the citrate groups, compared with the C2 group. A bile flow rate less than 0.3 microliter/min/g liver, 15 min after implantation, appeared to predict subsequent poor survival. There were no significant histological differences between biopsies taken from each group at the end of the transplant operation. Biochemical measures of liver function were best in animals that had received IC grafts, and functional damage after preservation was consistently greater in the C2 group than the citrate groups. The best results were obtained with grafts preserved with IC solution.     

Five-year survival results of subcutaneous low-dose immunotherapy with interleukin-2 alone in metastatic renal cell cancer patients

After the discovery of its essential role in anticancer immunity, IL-2 cancer immunotherapy has shown that comparable results may be obtained with different schedules, including intravenous high-dose IL-2 as a bolus or as a 24-hour intravenous infusion or prolonged subcutaneous injection of low-dose IL-2 with or without IFN-alpha. This study shows the long-term results obtained in 92 metastatic renal cell cancer (RCC) patients with low-dose subcutaneous IL-2, which was given at 3 million IU twice/day for 5 days/week for 6 consecutive weeks. In nonprogressing patients, a second cycle was planned after a 21-day rest period, followed by maintenance therapy consisting of 5 days of treatment every month until disease progression. Complete response (CR) was achieved in only 2/92 (2%) patients, and partial response (PR) was observed in 19 patients (21%). Therefore, the response rate (CR + PR) was 21/92 (23%), with a median duration of response of 25 months. Stable disease (SD) occurred in 37 patients (40%), whereas the other 34 (37%) had a progressive disease (PD). The response rate was significantly higher in patients with a disease-free interval of >1 year than in those with a lower interval, in patients with a high performance status (PS) than in those with a low PS, and in patients with sites of disease other than the liver. A 5-year survival was obtained in 9/92 (9%) patients, and the percent of survival was significantly higher in patients with a response or SD than in those with PD. The treatment was well tolerated in all patients. This study confirms that low-dose subcutaneous IL-2 alone in an effective and well tolerated therapy of metastatic RCC, with results comparable to those described with more aggressive and toxic IL-2 schedules.     

Interstitial hyperthermia of malignant brain tumors using implant heating system (IHS)

We have developed an implant heating system (IHS) for interstitial hyperthermia of brain tumors. IHS consists of three compartments: ferromagnetic implant with low Curie point, induction coil and generator to produce high frequency magnetic field. The device works as follows: It is heated up to a Curie temperature (Tc) by Eddy current under the magnetic field. Heat generated in the implant is conducted to the tumor tissue into which it has been implanted. To evaluate the effect of this hyperthermia, a brain tumor model was produced by innoculation of VX2 tumor cells and treated either by hyperthermia with IHS alone, chemotherapy with ACNU alone, or with a combination of both. The longest survival was obtained by the combined treatment, and significant prolongation of survival was found in the single treatment groups. In the Phase I clinical trial, one or several implants (1.8 mm X 15 mm, Tc = 68 degrees C) made of Fe-Pt alloy were placed in the tumor by CT guided stereotactic procedure, or manually during craniotomy. Hyperthermia of above 42 degrees C for 30 to 60 minutes twice a week was brought about in ten cases of malignant brain tumor. CT evaluation was made in nine cases treated for more than ten times in this way. Five out of the nine cases responded to this hyperthermia with irradiation. In conclusion, a safe, repeated and longterm treatment was possible without significant side effects. The hyperthermia with IHS may also be applicable to benign intracranial tumors and neoplasms in other part of body as well.     

Effect of cold-ischemia time on C-X-C chemokine expression and neutrophil accumulation in the graft liver after orthotopic liver transplantation in rats

BACKGROUND: The precise mechanisms leading to polymorphonuclear neutrophil (PMN) recruitment and activation in the extended cold-preserved liver after transplantation are not yet fully understood. METHODS: We histologically evaluated the number of accumulated PMNs in graft livers, with varying time periods of cold ischemia (1, 6, and 24 hr in University of Wisconsin solution at 4 degrees C), after liver transplantation in rats. Intragraft expression of macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC) mRNA, as well as immunohistochemical expression of MIP-2 and CINC in the graft liver, were investigated after reperfusion. The levels of MIP-2 and CINC in the hepatic vein, and tumor necrosis factor (TNF)-alpha, which stimulates these chemokine production, were also monitored. RESULTS: The number of accumulated PMNs in sinusoids significantly increased in the 24-hr cold-ischemia group within 3 hr after reperfusion, compared with the 1-hr and 6-hr groups. Serum MIP-2 levels in the 24-hr group significantly increased at 3, 6, and 12 hr after reperfusion, compared with the other groups. Intragraft MIP-2 mRNA was also up-regulated to a greater extent in the 24-hr group. Similarly, serum CINC levels in the 24-hr group significantly increased at 3 hr, compared with the 1-hr group. CINC mRNA also increased as cold-ischemia time was prolonged. Immunohistochemical staining revealed that hepatocytes were the main source of both MIP-2 and CINC protein. In addition, TNF-alpha in the hepatic vein was detected only in the 24-hr group after reperfusion. CONCLUSION: Extended cold preservation of the graft liver might up-regulate MIP-2 and CINC expression of hepatocytes, most probably through elevated TNF-alpha, and might contribute to PMN recruitment and activation after reperfusion.     

Pharmacokinetic evaluation of continuous infusion cisplatin

Cisplatin was administered to 11 patients as a continuous infusion, 25 mg/m2/day for 1 to 4 days. Total and filterable platinum in plasma were monitored for 12 courses and a pharmacokinetic study was carried out in 7 patients by computerized nonlinear least-squares analysis. Following interruption of the infusion, the decrease of plasma filterable platinum was biphasic, with initial and terminal half-life of 21.6 +/- 11.4 min and 31.7 +/- 27.1 hr. Filterable platinum was still detectable in plasma 24 hours after the end of infusion. The total AUC exposure of filterable platinum for 24 hrs, 48 hrs and 96 hrs infusion were 3.67 micrograms.hr/ml, 13.68 micrograms.hr/ml and 14.75 micrograms.hr/ml, which were at least 3-fold higher than that observed for the short-term infusion of equal dose in literature. Gastrointestinal toxicity was evaluated and compared with short-term infusion of equal dose. In the continuous-infusion patients, the reduction of vomiting was observed but the duration of nausea was not shortened.     

重复洗胃对有机磷农药中毒病人血胆碱脂酶活性的影响

为了探讨口服有机磷农药中毒后保留胃管重复洗胃对血胆碱酯酶活性的影响。将１８０例口服有机磷农药中毒病人随机分为观察和对照组，观察组９６例，保留胃管重复洗胃；对照组８４例，按常规法洗胃。观察两组每２４ｈ血胆碱酯酶活性变化。结果：轻度中毒时，两组血胆碱酶活性比较，差异无显著性（Ｐ〉０．０５）；中、重度中毒时，观察组血胆碱酯酶活性下降幅度小、回升快，与对照组比较，差异有极显著性（Ｐ〈０．０１）。提示保留胃     

Survival of primates in LD100 septic shock following steroid/antibiotic therapy

This study was designed to determine the effect of steroid/antibiotic treatment on the survival of baboons subjected to LD₁₀₀Escherichia coli shock. Fourteen baboons (Papio c. cynocephalus), randomly divided into three groups, were anesthetized and administered 2-hr infusions of LD₁₀₀ viable E. coli. Group A received E. coli alone; Group B was administered E. coli followed by infusions of both gentamicin sulfate (GS) (18 mg/kg) and methylprednisolone sodium succinate (MPSS) (75 mg/kg) during a 12-hr period. Group C was given E. coli plus GS (18 mg/kg) alone. Groups B and C baboons were also given GS intramuscularly, 4.5 mg/kg at 12 hr and twice daily for 3 days. Insensible fluid loss during the intial 12-hr period was replaced by minimal volumes of saline. Fully treated baboons (Group B) received steroid after 0.7 × 10¹⁰ organisms/kg body wt had been administered. All fully treated baboons survived; however, all animals of Groups A and C died within 42 hr. Systemic hypotension observed in every baboon within 2 hr was reversed in Group B animals. Hypoglycemia, hypoinsulinemia, anuria, and extensive adrenal pathology were prevented by steroid/antibiotic treatment. Serum creatinine and blood urea nitrogen concentrations increased in all baboons but returned to normal in the fully treated group. Increased survival may have been due in part to augmented antibacterial activity elicited by (a) improved peripheral distribution of the antibiotic and (b) stimulation of the bone marrow by the steroid. Findings demonstrate that the lethal pathophysiology of E. coli-induced shock is effectively prevented by combined steroid and antibiotic therapy.     

对Colles骨折运用Olders分类的临床统计分析

为评价Olders分类方法,4位医生分别用该方法对96例Colles骨折X线片进行分类,2周后重复一次。经过统计学处理后认为该分类在同一医生不同时间和不同医生互相之间的诊断符合率高。另外Olders方法中Ⅰ型、Ⅳ型的客观标准也很确切,故作者认为这一分类方法非常适合桡骨远端骨折的临床分类和诊断。     

Ischemic preconditioning of skeletal muscle improves tissue oxygenation during reperfusion

Ischemic preconditioning (IPC) renders tissue resistant to the deleterious effects of prolonged ischemia and reperfusion by prior exposure to brief, repeated periods of vascular occlusion. Although the mechanism by which IPC exerts its effect is unclear, it likely mediates an attenuation in capillary no-reflow. Tissue oximetry provides a potential technique to assess microvascular flow during ischemia/reperfusion and to measure the effect of IPC on muscle tissue oxygenation. The authors aimed to (a) establish that tissue oximetry is a sensitive method to assess the "no-reflow" phenomenon in skeletal muscle; and (b) to test the hypothesis that IPC would increase tissue oxygenation during reperfusion. In Group 1 (n = 5), the rabbit rectus femoris muscle was subjected to 2-hr ischemia. In Group 2 (n = 5), the muscle was subjected to 3.5-hr ischemia. In Group 3 (n = 6) the muscle was subjected to 3.5-hr ischemia preceded by three cycles of 10 min of pedicle occlusion and 10 min of reperfusion. Muscle oxygen tension was continuously monitored during the ischemic interval and for 6 hr of reperfusion. It was found that muscle oxygen tension in the flap at 5, 10, 30, 60, and 360 min after reperfusion was significantly decreased after 3.5-hr ischemia, compared with 2-hr ischemia (p < 0.05). Muscle oxygen tension at 30 and 60 min after reperfusion was significantly improved in the preconditioned group (p < 0.05). The results suggest that tissue oximetry is a sensitive method to assess tissue perfusion in reperfused skeletal muscle. Ischemic preconditioning improves tissue oxygenation during reperfusion following prolonged ischemia, which likely reflects an attenuation in capillary no-reflow.     

Potentiation of effects of anticancer agents by local electric pulses in murine bladder cancer

Electrochemotherapy is a novel cancer treatment in which electric pulses (EP) are used as a means of delivering anticancer agents to the cytoplasm of cancer cells (electroporation). The present study evaluates whether electrochemotherapy has in vitro and in vivo anticancer effects in murine bladder cancer. Using mouse bladder tumor cells (MBT-2 cells), in vitro electrochemotherapy was performed by applying EP to the cell suspension immediately after the addition of anticancer agents. The cytotoxicity of adriamycin (ADM), bleomycin (BLM) and cis-diamminedichloroplatinum(II) (CDDP) was determined by measuring succinate dehydrogenase (SD) activity in both electroporated and non-electroporated cells. In addition, intracellular concentrations of these anticancer agents were also measured. In the in vivo study, tumor-bearing C3H/He mice were treated with an intraperitoneal injection of anticancer agents followed by a local delivery of EP at the tumor site. Then, tumor growth rate (TGR) was determined and compared to that in the sham-treated control group, the EP-only group and the drug-only group. The in vitro study showed that, with electroporation, the cytotoxicity of BLM in electroporated cells was increased by as much as 95.7-fold compared to that of non-electroporated MBT-2 cells; CDDP showed only an increase of 1.8-fold and ADM showed no increase. After electroporation, the intracellular concentration of BLM, CDDP and ADM showed an increase of 120-, 1.7- and 0.8-fold, respectively. In electrochemotherapy for in vivo growing tumors, the potentiation of the antitumor effect was most prominent when combined with BLM, only slightly with CDDP, and totally absent with ADM. It is clear from in vitro and in vivo studies that, in a murine bladder tumor, the anticancer effect of BLM can be considerably potentiated by applying EP. Thus, BLM seems to be the most suitable anticancer agent for electrochemotherapy of bladder cancer. Received: 28 August 1999 / Accepted: 27 July 2000     

Evidence of increased gluconeogenesis during hemorrhage in fed and 24-hour food-deprived rats

Food withdrawal 24 hr before hemorrhage has been shown to increase experimental post-hemorrhage mortality, and survival is associated with the degree of hyperglycemia. Lack of hyperglycemic response has been attributed to depleted glycogen reserves after 24-hr food withdrawal. To investigate the effect of short-term food deprivation on glucose metabolism during hemorrhagic stress, glucose production (rate of appearance, Ra), glucose uptake (rate of disappearance, Rd), glucose clearance, and glucose recycling were investigated in fed and 24-hr food-deprived rats under basal conditions, and during hemorrhagic hypotension using 3-H3-U-C14-glucose. During hemorrhage, blood glucose levels were higher in fed rats. Hemorrhage induced a decrease in glucose clearance irrespective of nutritional state in both 24-hr starved animals and rats in the postprandial state. Calculated glucose recycling increased in both groups after hemorrhage. The results indicate that hemorrhagic stress induces a rapid increase in gluconeogenesis, as reflected by increased glucose recycling.