Factors associated with non-completion of palliative radiotherapy for spinal metastasis in patients with terminal cancer: a retrospective study.

BACKGROUND: Predictors of non-completion of radiotherapy (RT) should be identified to determine the optimal RT dose. Therefore, this study aimed to explore factors associated with non-completion of palliative RT in patients with terminal cancer. METHODS: In this retrospective study, patients with terminal cancer who received RT (not including single-fraction RT) for relief of pain caused by spinal metastasis were categorized into complete and incomplete groups. Baseline characteristics, hematologic test data [e.g., total lymphocyte count (TLC)], performance status, palliative performance scale (PPS) score, psoas muscle index (PMI), Charlson comorbidity index, and age-adjusted Charlson comorbidity index of the patients were compared between the two groups. RESULTS: The complete group comprised 58 patients (median age: 68 years; female/male: 17/41; number of irradiation fractions: ≥2 to <10, 20 patients; 10, 34 patients; and >10, 4 patients), and the incomplete group comprised 9 patients (median age: 68 years; female/male: 3/6; number of irradiation fractions: ≥2 to <10, 2 patients; 10, 7 patients; and >10, 0 patient). The proportion of patient death within 1 week or 1 month was higher in the incomplete group than in the complete group. Compared with that in the incomplete group, TLC measured 1 week before RT (pre-TLC) and PMI recorded before RT were significantly higher in the complete group (P=0.013 and P=0.012, respectively). In multivariable analyses, pre-TLC was significantly associated with the incomplete group (P=0.048). Compared with the complete group, the incomplete group included several patients whose PPS scores rapidly decreased. CONCLUSIONS: Pre-TLC can predict non-completion of palliative RT in patients with terminal cancer.

Validation of the Japanese version of the 8-item Chronic Pain Acceptance Questionnaire (CPAQ-8).

This study aimed to examine the reliability and validity of the Japanese version of the Chronic Pain Acceptance Questionnaire (CPAQ-8J). A total of 108 outpatients with chronic pain completed the CPAQ-8 questionnaire, along with the Acceptance and Action Questionnaire-II, Hospital Anxiety and Depression Scale, Pain Disability Assessment Scale, Numerical Rating Scale, and EuroQol 5 dimensions 5-level. Confirmatory factor analyses examined the factor structure. Results indicated that the CPAQ-8J comprised a two-component factor structure. Correlations between the CPAQ-8J and each variable were as expected, except between the "pain willingness" subscale and other scales ; thus, the CPAQ-8J had a certain degree of convergent validity. Internal consistency and test-retest reliability suggest that the CPAQ-8J is reliable. The psychometric properties of the CPAQ-8J meet a certain standard ; meanwhile, some issues must be addressed for its practical application. Further research should consider the influence of cultural characteristics in practical application. J. Med. Invest. 70 : 88-93, February, 2023.

A case of glossopharyngeal neuralgia successfully treated with levetiracetam.

BACKGROUND: Glossopharyngeal neuralgia is a condition that causes severe pain in the throat during swallowing. Although carbamazepine is a viable option for treating glossopharyngeal neuralgia, there are minimal data regarding the effect of alternative agents to treat it. We report on glossopharyngeal neuralgia, which is successfully controlled by levetiracetam. PRESENTATION: A woman in her 70s checked into our hospital with a chief complaint of neck pain lasting 5 years. She had a history of carbamazepine-induced interstitial pneumonia. As a result, we prescribed oral levetiracetam 1000 mg daily in addition to mirogabalin, which was previously prescribed. This effectively reduced the numerical rating scale from 9 to 1 with no adverse effects. Finally, she underwent microvascular decompression, and her symptoms were resolved. CONCLUSION: Levetiracetam may be an option for patients with glossopharyngeal neuralgia who cannot receive carbamazepine. However, levetiracetam is for off-label use according to the Japanese medical system.

Differences in Attitudes and Practices of Cancer Pain Management between Medical Oncologists and Palliative Care Physicians.

This study aimed to evaluate whether there are differences in the attitudes and practices of cancer pain manage-ment between medical oncologists and palliative care physicians. An online nationwide survey was used to collect responses from board-certified medical oncologists and palliative care physicians in Japan. The survey questionnaire comprised 30 questions. The differences in responses between medical oncologists and palliative care physicians were examined. Out of the 1,227 questionnaires sent, 522 (42.5%) were returned. After apply-ing the exclusion criteria, 445 questionnaires (medical oncologists: n = 283; palliative care physicians: n = 162) were retained for analysis. Among the questions about potential barriers to optimal cancer pain man-agement, both medical oncologists and palliative care physicians considered the reluctance of patients to take opioids due to fear of adverse effects as the greatest barrier. Significantly different ratings between medical oncologists and palliative care physicians were observed on 5 of the 8 questions in this area. Significantly differ-ent ratings were observed for all questions concerning pain specialists and their knowledge. For effective cancer pain management, it is important to account for differences in attitudes and practice between medical oncolo-gists and palliative care physicians.

Pilot study of a basic individualized cognitive behavioral therapy program for chronic pain in Japan.

BACKGROUND: Chronic pain is a major health problem, and cognitive behavioral therapy (CBT) is its recommended treatment; however, efforts to develop CBT programs for chronic pain and assess their feasibility are remarkably delayed in Asia. Therefore, we conducted this pilot study to develop a basic individualized CBT for chronic pain (CBT-CP) and assessed its feasibility for use in Japan. METHODS: Our study was an open-labeled before-after trial without a control group conducted cooperatively in five Japanese tertiary care hospitals. Of 24 outpatients, 15, age 20-80, who experienced chronic pain for at least three months were eligible. They underwent an eight-session CBT-CP consisting of relaxation via a breathing method and progressive muscle relaxation, behavioral modification via activity pacing, and cognitive modification via cognitive reconstruction. The EuroQol five-dimensional questionnaire five level (EQ5D-5 L) assessment as the primary outcome and quality of life (QOL), pain severity, disability, catastrophizing, self-efficacy, and depressive symptoms as secondary outcomes were measured using self-administered questionnaires at baseline, post-treatment, and 3-month follow-up. Intention-to-treat analyses were conducted. RESULTS: Effect size for EQ5D-5 L score was medium from baseline to post-treatment (Hedge's g = - 0.72, 90% confidence interval = - 1.38 to - 0.05) and up to the 3-month follow-up (g = - 0.60, CI = - 1.22 to 0.02). Effect sizes for mental and role/social QOL, disability, catastrophizing, self-efficacy, and depressive symptoms were medium to large, although those for pain severity and physical QOL were small. The dropout rate was acceptably low at 14%. No severe adverse events occurred. CONCLUSION: The findings suggest that CBT-CP warrants a randomized controlled trial in Japan. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), UMIN000020880. Registered on 04 February 2016.

A Multidisciplinary Approach to the Management of Chronic Pain through a Self-managed Behavioral Exercise Program : A Pilot Study in Japan.

We conducted this study to determine the short-term treatment outcomes of multidisciplinary approaches to chronic pain management for outpatients in Japan. We evaluated pain reduction and improvement in quality of life (QOL) after treatment. We analyzed 32 patients who had experienced intractable chronic pain for > 3 months. The patients received multidisciplinary therapeutic self-managed exercise instructions and then underwent evaluations 1 and 3 months after the treatment. We used the Pain Disability Short Form-36 (SF-36), Pain Catastrophizing Scale (PCS), and Pain Disability Assessment Scale (PDAS) to evaluate QOL. Although the pain levels were the same before and after the physical exercise program, the patients showed significant improvements in physical function on the SF-36 (48.5 vs. 54.5, 3 months vs. 1 month; p=0.0124), the magnification subscale on the PCS (6.8 vs. 5.9, 1 month vs. before; p=0.0164) and the PDAS (29.2 vs. 23.4, 3 months vs. before; p=0.0055). Chronic pain should be treated with a biopsychosocial approach, but time constraints and costs have limited the implementation of multidisciplinary and behavioral approaches to chronic pain management. Our findings demonstrate that clinical improvements are possible for patients with chronic pain, using multidisciplinary team resources widely available in Japanese clinical practice.

Validation of the Edmonton Symptom Assessment System: Ascites Modification.

CONTEXT: Few patient-reported outcomes are available to measure the symptoms associated with malignant-related ascites in patient care and clinical research. Although the Edmonton Symptom Assessment System: Ascites Modification (ESAS:AM) is a brief tool to measure symptoms associated with malignant-related ascites, it remains to be fully validated. OBJECTIVES: The objective of the study was to validate the ESAS:AM in Japanese cancer patients. METHODS: We assessed the internal consistency, test-retest reliability, concurrent validity, and construct validity in 292 Japanese adult patients with cancer. They completed Japanese versions of the ESAS:AM, M.D. Anderson Symptom Inventory, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, and abdominal pain/ascites subscales of the EORTC Core Quality of Life Questionnaire, 26-item pancreatic cancer module. RESULTS: Cronbach's alpha coefficient of the ESAS:AM was 0.89. The intraclass correlation coefficient on test-retest examination of its total score was 0.93 (P < 0.001). Pearson correlation coefficients of the total score of the ESAS:AM with the total score of the M.D. Anderson Symptom Inventory and abdominal pain/ascites subscales of the EORTC Core Quality of Life Questionnaire, 26-item pancreatic cancer module ranged from 0.44 to 0.81 (P < 0.001) and those with global health status/quality of life and functional subscales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 ranged from -0.40 to -0.61 (P < 0.001). The total scores of the ESAS:AM were significantly higher in 20 patients with symptomatic ascites (34 [SD, 26]) than 267 patients without symptomatic ascites (23 [SD, 19]) (P = 0.018). CONCLUSION: The ESAS:AM is a reliable and valid tool for measuring symptoms associated with malignant-related ascites and can be used in daily patient care and future epidemiological studies and clinical trials.

The Effect of Guidance regarding Home Exercise and ADL on Adolescent Females Suffering from Adverse Effects after HPV Vaccination in Japanese Multidisciplinary Pain Centers.

Background. Two prophylactic papillomavirus (HPV) vaccines have been available for primary prevention of cervical cancer. Although serious adverse effects (AE) were rare, more than 230 women have been suffering from severe AEs such as persistent pain and headache in Japan. Our research group started to treat adolescent females suffering from the AEs. Objective. To survey the characteristics of and the effects of cognitive behavioral therapy on adolescent female suffering from the AEs in Japanese multidisciplinary pain centers. Methods. One hundred and forty-five patients suffering from the AEs were reviewed retrospectively and 105 patients of them were provided guidance on home exercise and activities of daily living based partially on a cognitive-behavioral approach. The intensity of pain was rated by the patients using a numerical rating scale (NRS). Furthermore, the Hospital Anxiety and Depression Scale (HADS) and the Pain Catastrophizing Scale (PCS) were used. Results. Eighty out of the 105 patients who received the guidance were followed up, 10 displayed a marked improvement, and 43 showed some improvement. Conclusions. Guidance on home exercise and activities of daily living based on a cognitive-behavioral approach alleviated the AEs that women suffered from after HPV vaccination in Japan.

Establishing Cutoff Points for Defining Symptom Severity Using the Edmonton Symptom Assessment System-Revised Japanese Version.

CONTEXT: Symptom screening is important for appropriate symptom management. It remains uncertain as to which scores on the Edmonton Symptom Assessment System-Revised (ESAS-r) comprise the optimal cutoff points to determine symptom severity for Japanese cancer patients. OBJECTIVES: To investigate optimal cutoff points for individual ESAS-r items for detecting symptom severity and to evaluate the screening performance of the ESAS-r depression item in Japanese cancer patients. METHODS: We recruited cancer patients receiving palliative care from five tertiary acute hospitals in Japan. We asked participants to complete the ESAS-r Japanese version, Verbal Rating Symptom Severity Scale, and Quick Inventory of Depressive Symptomatology-Self-Report Japanese version. We calculated sensitivity and specificity for detecting severe and moderate/severe symptoms evaluated by the Verbal Rating Symptom Severity Scale at different cutoff points of the ESAS-r. We also calculated sensitivity and specificity for detecting both the presence of depression and moderate/severe depression evaluated by the Quick Inventory of Depressive Symptomatology-Self-Report at various cutoff points for the depression item of the ESAS-r Japanese version. RESULTS: A total of 292 participants completed the questionnaire. For most of the ESAS-r symptoms, cutoff points to achieve the best balance between sensitivity and specificity were 5-7 for determining severe intensity and 3-4 for determining moderate/severe intensity. For the ESAS-r depression item, a cutoff point of 2 achieved the best balance between sensitivity and specificity for detecting both the presence of depression and moderate/severe depression. CONCLUSION: The ESAS-r Japanese version can accurately represent the severity of many symptoms. The cutoff points established for determining the level of symptom severity using ESAS-r provides a guide for symptom management in Japanese cancer patients.

Validation of the Japanese Version of the Edmonton Symptom Assessment System-Revised.

CONTEXT: The Edmonton Symptom Assessment System-revised (ESAS-r) is a brief and widely used symptom measurement tool. OBJECTIVES: To validate the Japanese version of the ESAS-r in Japanese patients with cancer. METHODS: We assessed the internal consistency, test-retest reliability, concurrent validity, and known-group validity in 292 Japanese adult patients with cancer. They completed Japanese versions of the ESAS-r, M. D. Anderson Symptom Inventory, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. RESULTS: Cronbach's alpha coefficient of the Japanese version of the ESAS-r was 0.87. The intraclass correlation coefficient in the test-retest examination ranged from 0.82 to 0.91 for each symptom score and was 0.90 for the total score. Pearson correlation coefficients of each ESAS-r symptom score with corresponding M. D. Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 items ranged from 0.45 to 0.80. The total score of the ESAS-r was significantly higher in patients with an Eastern Cooperative Oncology Group performance status of 2-4 than in those with a performance status of 0 and 1 (P < 0.0001). CONCLUSION: The Japanese version of the ESAS-r is a reliable and valid tool for measuring symptoms in Japanese adult patients with cancer.

Establishment of a liaison clinic for patients with intractable chronic pain.

BACKGROUND: A multidisciplinary approach has been shown to be effective for the treatment of intractable pain. However, few hospitals in Japan have established liaison clinics for such patients. In this study, we investigated the short-term results of a liaison clinic for patients with intractable chronic pain. METHODS: Study participants comprised 53 outpatients (20 men, 33 women) with intractable chronic pain who visited our hospital between April 2012 and March 2013. At baseline, patients completed a self-reported questionnaire and provided demographic and clinical information. Experts in various fields (anesthesia, orthopedic surgery, psychiatry, physical therapy, and nursing) conducted examinations of patients and attended a weekly conference during which patients' physical, psychological, and social problems were discussed and courses of treatment were determined. All patients were assessed using the Numerical Rating Scale (NRS), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS), and Pain Disability Assessment Scale (PDAS). Eligibility for the pain liaison outpatient clinic was evaluated using multiple logistic regression analysis. RESULTS: After a 6-month follow-up period, no significant changes were seen in scores for the NRS, PDAS, or HADS for depression. In contrast, scores for both the PCS and HADS for anxiety were significantly reduced after 6 months of treatment (p < 0.05). HADS for anxiety was identified as a factor related to patient resistance to attending the pain liaison outpatient clinic (p < 0.05). CONCLUSIONS: This liaison clinic for patients with intractable chronic pain was able to improve patient anxiety. Severe anxiety at the initial visit represented a risk factor for dropout from the clinic.

Refractory cachexia is associated with increased plasma concentrations of fentanyl in cancer patients.

BACKGROUND: An appropriate plasma concentration of fentanyl is the key to achieving good pain control in cancer patients. Cachexia, a multifactorial syndrome, is known to affect drug-metabolizing enzymes. However, the fentanyl concentrations in the blood of patients with cachexia have not been analyzed. The aim of this study was to evaluate the influence of cancer cachexia on dose-adjusted plasma fentanyl concentrations in cancer patients. METHODS: Blood was collected from 21 Japanese cancer patients treated with a 24-hour trans-dermal fentanyl patch during the steady state of fentanyl plasma concentration. Plasma fentanyl concentrations were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and the levels were adjusted with the dose of fentanyl. Laboratory data were collected, and the cachexia stage was determined, based on study by Fearon et al. Multiple regression analysis was performed to identify the factors that affected fentanyl plasma concentrations. RESULTS: Eight patients were classified as precachexia, nine as cachexia, and four as refractory cachexia, and the median dose-adjusted fentanyl concentrations (ng/mL per mg/kg/day) were 27.5, 34.4, and 44.5, respectively. The dose-adjusted fentanyl concentration in patients with refractory cachexia was higher than that in patients with precachexia (Kruskal-Wallis test and post hoc Mann-Whitney U-test, P<0.01). The factors that were found to possibly affect the dose-adjusted concentration of fentanyl included aspartate aminotransferase, C-reactive protein, and estimated glomerular filtration rate, when analyzed as six independent variables (multiple regression analysis, P<0.05). CONCLUSION: The dose-adjusted plasma concentrations of fentanyl increased with progression of cancer cachexia. Such an increase is associated with a multifactorial and systemic syndrome in cancer cachexia patients, including lower albumin, higher C-reactive protein, and impaired kidney function. In patients with cancer cachexia, we suggest that evaluation of cancer cachexia might help pain management when using a transdermal fentanyl patch in palliative care.

Living will interest and preferred end-of-life care and death locations among Japanese adults 50 and over: a population-based survey.

The main purpose of this study was to determine the relationships between Japanese individuals' interest in living wills and their preferred end-of-life care and death locations. Questionnaires were mailed to 1,000 individuals aged >50 to measure these 2 factors. We examined the associations between the respondents' characteristics and their preferred care and death locations by using multinomial logistic regression models. The response rate was 74%. Home was the most frequently preferred place for end-of-life care (64%), and a palliative care unit (PCU) was the most commonly preferred place to die (51%). Living will interest was associated with a preference for care (odds ratio [OR] 4.74, 95% confidence interval [CI] 1.95-12.1) and death (OR 2.75, 95% CI 1.70-4.47) in a PCU rather than a hospital, but it was not associated with the choice between receiving care or dying at home instead of a hospital. We must consider why Japanese people think home death is impracticable. The Japanese palliative care system should be expanded to meet patients' end-of-life needs, and this includes not only facilitating home care but also increasing access to PCU care.

Antinociceptive effects of intrathecal landiolol injection in a rat formalin pain model.

Perioperative beta-blocker administration has recently been recommended for patients undergoing cardiac or other surgery due to the beneficial cardiovascular effects of these agents. In addition, some studies have reported that perioperatively administered beta-blockers also have analgesic effects. In this study, to investigate the antinociceptive effects and the analgesic profile of landiolol, we examined the effects of intrathecal landiolol administration on nociceptive pain behavior and c-fos mRNA expression (a neural marker of pain) in the spinal cord using a rat formalin model. We found that pain-related behavior was inhibited by intrathecal landiolol administration. Moreover, the increase in c-fos mRNA expression on the formalin-injected side was less pronounced in rats administered landiolol than in saline administered controls. Thus, intrathecal administration of landiolol exhibited antinociceptive effects. Further investigation of the antinociceptive mechanism of landiolol is required.

Expansion of CpG methylation in the SFRP2 promoter region during colorectal tumorigenesis.

Secreted frizzled-related protein 2, (SFRP2) is a Wnt inhibitor whose promoter CpGs were recently found to be methylated at high frequency in colorectal cancers (CRCs). We hypothesized that the pattern of SFRP2 methylation may differ throughout the promoter during progressive tumorigenesis. Using combined bisulfite restriction analysis (COBRA), two methylation-sensitive regions (Regions A and B) of the SFRP2 promoter were investigated in 569 specimens of colorectal tissue:222 CRCs, 103 adenomatous polyps (APs), 208 normal colonic mucosa from CRC patients (N-Cs), and 36 normal colonic mucosa from subjects with no evidence of colorectal neoplasia at colonoscopy (N-Ns). Extensive (including both Regions A and B) and partial (either Region A or B) SFRP2 methylation levels were found in 61.7% and 24.8% of CRCs, 8.7% and 37.9% of APs, 3.9% and 39.9% of N-Cs, and 0% and 30.6% of N-Ns, respectively. Extensive methylation of the SFRP2 promoter was present primarily in CRCs, while partial methylation was common in APs. Whereas APs with the KRAS mutant showed no correlation to any pattern of SFRP2 methylation, extensive methylation of the SFRP2 promoter was significantly associated with KRAS mutant CRCs (p＜.0001), suggesting that genetic alteration in the RAS-RAF pathway might precede the spread of CpG methylation through the SFRP2 promoter, which is observed in over 60% of advanced colorectal tumors.

Role of heme oxygenase-1 in protection of the kidney after hemorrhagic shock.

Hemorrhagic shock followed by resuscitation (HSR) causes oxidative stress, which results in multiple organ damage. The kidney is one of the target organs of HSR-mediated oxidative tissue injury. Heme oxygenase (HO)-1, the rate-limiting enzyme in heme catabolism, is induced by oxidative stress; it protects against oxidative tissue injuries. The aim of the present study was to examine the role of renal HO-1 induction after HSR. Rats were subjected to hemorrhagic shock to achieve a mean arterial pressure of 30 mmHg for 60 min, followed by resuscitation with the shed blood. HSR resulted in a significant increase in functional HO-1 protein in the tubular epithelial cells of the kidney, whereas HSR resulted in only a slight increase in gene expression of tumor necrosis factor (TNF)-alpha and inducible nitric oxide synthase (iNOS), and in protein expression of activated caspase-3 solely in renal cells where HO-1 expression was absent. HSR also resulted in a significant increase in Bcl-2 gene expression. Pretreatment of HSR animals with tin-mesoporphyrin (0.5 micromol/kg), a specific competitive inhibitor of HO activity, resulted in a significant decrease in HO activity and exacerbated tissue inflammation and apoptotic cell death as judged by the marked increase in expression of TNF-alpha and iNOS, and in activated caspase-3-positive cells, and the significant reduction in Bcl-2 expression, respectively. These findings indicate that HO-1 induction is an adaptive response to HSR-induced oxidative stress and is essential for protecting tubular epithelial cells from oxidative damage through its anti-inflammatory and anti-apoptotic properties.

Nonimmersive virtual reality mirror visual feedback therapy and its application for the treatment of complex regional pain syndrome: an open-label pilot study.

OBJECTIVE: Chronic pain conditions such as phantom limb pain and complex regional pain syndrome are difficult to treat, and traditional pharmacological treatment and invasive neural block are not always effective. Plasticity in the central nervous system occurs in these conditions and may be associated with pain. Mirror visual feedback therapy aims to restore normal cortical organization and is applied in the treatment of chronic pain conditions. However, not all patients benefit from this treatment. Virtual reality technology is increasingly attracting attention for medical application, including as an analgesic modality. An advanced mirror visual feedback system with virtual reality technology may have increased analgesic efficacy and benefit a wider patient population. In this preliminary work, we developed a virtual reality mirror visual feedback system and applied it to the treatment of complex regional pain syndrome. DESIGN: A small open-label case series. Five patients with complex regional pain syndrome received virtual reality mirror visual feedback therapy once a week for five to eight sessions on an outpatient basis. Patients were monitored for continued medication use and pain intensity. RESULTS: Four of the five patients showed >50% reduction in pain intensity. Two of these patients ended their visits to our pain clinic after five sessions. CONCLUSION: Our results indicate that virtual reality mirror visual feedback therapy is a promising alternative treatment for complex regional pain syndrome. Further studies are necessary before concluding that analgesia provided from virtual reality mirror visual feedback therapy is the result of reversing maladaptive changes in pain perception.

Site-specific induction of intestinal hypoxia-inducible factor-1α after hemorrhagic shock.

The intestine is a major target organ in hemorrhagic shock (HS)-induced tissue injury. Hypoxia-inducible factor (HIF)-1α is the primary transcription factor responsible for regulating cellular response to changes in oxygen tension. Since HS is an acute hypoxic insult, the present study examined changes in the gene expression of HIF-1α in various regions of the intestine, as well as the distribution of HIF-1α protein in the intestinal cells of a rat model of HS. Levels of HIF-1α mRNA were marginally detectable in the intestine of sham-operated control animals, but obviously induced following HS. Duodenal, jejunal and colonic levels of HIF-1α mRNA robustly increased and reached a maximum during the ischemic phase of HS, followed by a rapid decrease almost to control levels during the early phase of resuscitation. The induction of HIF-1α mRNA was maximal in the duodenum. In contrast to the duodenum, jejunum and colon, in the ileum the HIF-1α mRNA level did not increase after HS. Consistent with enhanced HIF-1α gene expression, HIF-1α protein was expressed in the mucosal cells of the duodenum, jejunum and colon, but not in the ileum following HS. These findings indicate that intestinal HIF-1α expression was up-regulated at both the transcriptional and protein level in a site-specific manner in this rat model of HS. Differential regulation of HIF-1α expression along the longitudinal axes of the intestine might be a determinant of the adaptive response to HS-induced intestinal damage.