Construction of a model for predicting creatinine clearance in Japanese patients treated with Cisplatin therapy.

BACKGROUND/AIM: There exist various useful predictive models, such as the Cockcroft-Gault model, for estimating creatinine clearance (CLcr). However, the prediction of renal function is difficult in patients with cancer treated with cisplatin. Therefore, we attempted to construct a new model for predicting CLcr in such patients. PATIENTS AND METHODS: Japanese patients with head and neck cancer who had received cisplatin-based chemotherapy were used as subjects. A multiple regression equation was constructed as a model for predicting CLcr values based on background and laboratory data. RESULTS: A model for predicting CLcr, which included body surface area, serum creatinine and albumin, was constructed. The model exhibited good performance prior to cisplatin therapy. In addition, it performed better than previously reported models after cisplatin therapy. CONCLUSION: The predictive model constructed in the present study displayed excellent potential and was useful for estimating the renal function of patients treated with cisplatin therapy.

Cyclin D1/cdk4, estrogen receptors α and ß, in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric carcinogenesis: immunohistochemical study.

Hyperproliferative cell growth due to cyclin D1/cdk4, marker of cellular proliferation, is considered to be regulated by the expression of estrogen receptors (ERs). We investigated the immunohistochemical expression of cyclin D1/cdk4 and ERs in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced rat gastric carcinogenesis. The gastric cancer incidence and expression of cyclin D1/ckd4 in gastric carcinogenesis were significantly higher in males than females. Although the ERα expression index was similar in both sexes, the ERß expression in preneoplastic hyperplastic lesions as well as gastric cancers was significantly higher in females than in males. The present study revealed a gender difference in MNNG-induced rat gastric carcinogenesis that seemed to involve the sex difference in cyclin D1/cdk4 expression, and ERß expression became evident at the preneoplastic promotion stage in gastric carcinogenesis.

Interleukin-6 as an independent predictor of future cardiovascular events in high-risk Japanese patients: comparison with C-reactive protein.

Inflammation is associated with the development of atherosclerotic vascular lesions and some inflammatory parameters are used as cardiovascular (CV) risk markers. The present study was designed to assess the predictive power of interleukin (IL)-6 for future CV events. In 121 Japanese patients with multiple CV risk factors and/or disease, serum concentrations of IL-6 and high sensitive C-reactive protein (hs-CRP) were measured. During follow-up periods (mean, 2.9 years) after the baseline assessment, 50 patients newly experienced CV events such as stroke/transient ischemic attack (n=10), heart failure hospitalization (n=6), acute coronary syndrome (n=7), and revascularization for coronary artery disease (n=15) and peripheral arterial disease (n=12). The serum level of IL-6, but not hs-CRP, was significantly higher in patients who had CV events than in event-free subjects (3.9±2.6 and 3.0±2.2 pg/mL, P=0.04). When the patients were divided into three groups by tertiles of basal levels of IL-6 (<1.85, 1.85-3.77, and ≥3.77 pg/mL), cumulative event-free rates by the Kaplan-Meier method were decreased according to the increase in basal IL-6 levels (65%, 50%, and 19% in the lowest, middle, and highest tertiles of IL-6, respectively; log-rank test, P=0.002). By univariate Cox regression analysis, previous CV disease, creatinine clearance, and serum IL-6 levels were significantly associated with CV events during follow-up. Among these possible predictors, the highest tertile of IL-6 was only an independent determinant for the morbidity in the multivariate analysis (hazard ratio 2.80 vs. lowest tertile, P=0.006). These findings indicate that IL-6 is a powerful independent predictor of future CV events in high-risk Japanese patients, suggesting its predictive value is superior to that of hs-CRP.

Higher pAkt expression predicts a significant worse prognosis in glioblastomas.

phosphorylated-Akt (pAkt) plays an important role in tumorigenesis through promotion of cell survival by inhibiting apoptosis and mediating cell proliferation. Higher expression of pAkt has been reported to be associated with an unfavorable prognosis in several malignant tumors. In this study, the prognostic value of pAkt expression was investigated in glioblastomas by using immunohistochemical methods. Tissue sections obtained from 64 patients with glioblastoma were evaluated. The mean and median follow-up period was 16.2 +/- 12.4 and 12 months, respectively (range: from 1 to 62 months). pAkt expression levels were determined by immunohistochemical staining and evaluated for cell positivity. Positive staining was defined when more than 50% of the tumor cells were stained in each section. The correlation between expression of pAkt and overall survival rate was assessed. Glioblastomas showed either or both cytoplasmic and nuclear positive findings for pAkt. A total of 29.7% (19/64) of tissue specimens had greater than 50% positivity. The median survival periods of the patients with pAkt positive and negative tumor were 10 and 14 months, respectively. Two years overall survival rate of the pAkt positive and negative patients were 0% and 24.4%, respectively. Survival rate of the patients with pAkt positive tumor was significantly lower than that of the patients with pAkt negative tumors (p = 0.004). Multivariate analysis showed that extent of surgery was the strongest factor for survival (p = 0.01) and the pAkt expression was the secondly strongest factor (p = 0.06). These results suggest that the higher expression of pAkt the poorer prognosis in patients with glioblastoma.

Are the effects of alpha-glucosidase inhibitors on cardiovascular events related to elevated levels of hydrogen gas in the gastrointestinal tract?

The major side-effect of treatment with alpha-glucosidase inhibitors, flatulence, occurs when undigested carbohydrates are fermented by colonic bacteria, resulting in gas formation. We propose that the cardiovascular benefits of alpha-glucosidase inhibitors are partly attributable to their ability to neutralise oxidative stress via increased production of H(2) in the gastrointestinal tract. Acarbose, which is an alpha-glucosidase inhibitor, markedly increased H(2) production, with a weaker effect on methane production. Our hypothesis is based on our recent discovery that H(2) acts as a unique antioxidant, and that when inhaled or taken orally as H(2)-dissolved water it ameliorates ischaemia-reperfusion injury and atherosclerosis development.

Nuclear survivin expression predicts poorer prognosis in glioblastoma.

Survivin is a member of the inhibitor of apoptosis family, and is expressed in various malignant tumors. Survivin overexpression has been reported to be a poorer prognostic factor in various malignancies. However, the prognostic value of survivin expression in patients with glioblastoma is still controversial. Therefore, in this study the role of survivin as a predictor for survival was investigated in patients with glioblastoma. Tissue specimens were obtained from 66 patients with glioblastoma treated with radiotherapy. Survivin expression was detected by an immunohistochemical method. Nuclear and cytoplasm survivin scores were defined by using the cell positivity and staining intensity. The scores were defined as follows, 0 (no staining), 1 (less than 50% of cell positivity and any staining), 2 (more than 50% of cell positivity and weak to moderate intensity) and 3 (more than 50% of cell positivity and strong intensity). The correlation between survivin scores and the overall survival rate was evaluated. Nuclear and cytoplasm survivin staining were noted in 47 and 58 patients, respectively. The number of patients with nuclear survivin score of 0, 1, 2 and 3, were 19 (28.8%), 26 (39.4%), 9 (13.6%) and 12 (18.2%), respectively. The 3-year overall survival rate of the nuclear survivin score 3 was 0%, significantly lower than the 11.6% of the nuclear survivin score

Sertoli-Leydig cell tumor of the testis in a Sprague-Dawley rat.

A rare intratubular gonadal stromal tumor was present in the testis of a 7-wk-old male Sprague-Dawley rat. The tumor comprised an intratubular mixture of 2 types of tumor cells with intercellular junctions: the predominant tumor cells were consistent with a Sertoli cell origin, and cells comprising the minor population were situated on basolateral side of the tubuli, consistent with a Leydig cell origin. The neoplastic Sertoli cells had large pleomorphic nuclei and clear cytoplasm with many tubulovesicular cristae and free ribosomes, whereas the neoplastic Leydig cells showed relatively small pleomorphic nuclei, dark cytoplasm with rich smooth endoplasmic reticulum, numerous mitochondria, and lipid droplets. Occasionally, a few transitional type neoplastic cells were observed. The presence of a thick or multilayered basement membrane was confirmed except in tumor-infiltrative lesions. The present case was considered to be a testicular mixed tubular Sertoli-Leydig cell tumor in a Sprague-Dawley rat.

Clinical usefulness of CYFRA 21-1 for esophageal squamous cell carcinoma in radiation therapy.

AIM: The aim of this study was to examine the clinical usefulness of cytokeratin 19 fragments (CYFRA 21-1) compared with squamous cell carcinoma (SCC) antigen in patients with esophageal cancer treated with radiation therapy. METHODS: Fifty-one patients with stage I-IV esophageal cancer were evaluated. CYFRA 21-1 and SCC antigen serum levels were measured at the start and the end of radiation therapy. RESULTS: CYFRA 21-1 (> 3.5 ng/mL) and SCC antigen (> 1.5 ng/mL) before radiation therapy were elevated in 63% and 53% of the patients, respectively. The CYFRA 21-1 levels were significantly correlated with TNM stages, tumor depth and lymph node metastasis (P = 0.0003, P = 0.019 and P = 0.019, respectively), whereas no correlation was observed between SCC antigen and these factors. The values of CYFRA 21-1 in all patients who survived without recurrence were under the cutoff level at the end of treatment, but the values in all patients with locoregional recurrence were above the level. However, there was no significant correlation between SCC antigen level at the end of treatment and any clinical outcome. CONCLUSIONS: The results suggest that the evaluation of CYFRA 21-1 would be useful not only for assessment before radiation therapy but also for monitoring after radiation therapy in the treatment for esophageal cancer.

Localization of Ang-1, -2, Tie-2, and VEGF expression at endothelial-pericyte interdigitation in rat angiogenesis.

Endothelial cells and pericytes play critical role in angiogenesis, which is controlled, in part, by the angiopoietin (Ang)/Tie-2 system and vascular endothelial growth factor (VEGF). Here, we investigated Ang, Tie-2, and VEGF expression within endothelial cells and pericyte interdigitations (EPI), which consist of cytoplasmic projections of pericytes and corresponding endothelial indentations. After subcutaneous implantation of a thermoreversible gelation polymer disc in rats, the capillary density was low on day 5, increased to a peak on day 7, and then decreased on days 10-20. A small number of EPI were observed on day 5, then increased sharply to a peak on day 10, but had decreased on day 20. Light and electron microscopy immunohistochemical and RNA in situ hybridization analyses revealed that Tie-2 localized at endothelial cells, and Ang-2 localized at endothelial cells and pericytes, while Ang-1 and VEGF localized at pericytes, and Ang-1 was most intensely observed at EPI of pericytes. Conventional quantitative RT-PCR and Western blot analyses revealed that the level of Ang-1 was low on days 5-7, then increased on days 10-20, while the level of VEGF was high on days 5-10, but had decreased on day 20. The level of Ang-2 remained high and Tie-2 remained at the level of the control on days 5-20. The present study showed that the angiogenic phase might be initiated by increases in Ang-2 and VEGF, while the microvessel maturation phase might be initiated by a relative increase in Ang-1 and a decrease in VEGF. Moreover, EPI might serve as a pathway for the Ang-1/Tie-2 system, with VEGF promoting pericyte recruitment for microvascular integrity.

How do we interpret the answer "Neither" when physicians ask patients with cancer "Are you depressed or not?".

OBJECTIVES: The aim of this study was to clarify how physicians should interpret the answer "neither" to the single-question interview, "Are you depressed or not?" PATIENTS AND METHODS: Two hundred fifty-one patients with cancer were studied. The patients were directly interviewed, choosing one answer among these three: "Yes, I am depressed"; "No, I am not depressed"; or "Neither." After this, the patients completed the Hospital Anxiety and Depression Scale (HADS). The threshold of 11 or greater on HADS was used for adjustment disorder and major depressive disorder. RESULTS: All patients could reply to the single question, but 10 patients did not complete HADS. Among 83, 81 and 77 patients who answered "yes," "neither," and "no," respectively, 75 (90%), 43 (65%), and 9 (12%) patients scored 11 or more on HADS. The mean score of HADS was 12.2 in patients who answered "neither," significantly higher than that of the "no" group (p < 0.0001) and significantly lower than that of the "yes" group (p < 0.0001). CONCLUSION: Patients who answered "neither" frequently scored in a high enough range to warrant further investigation for adjustment or depressive disorder.

Prenatal 3,3',4,4',5-pentachlorobiphenyl exposure modulates induction of rat hepatic CYP 1A1, 1B1, and AhR by 7,12-dimethylbenz[a]anthracene.

We previously reported the finding that prenatal exposure to a relatively low dose of PCB126 increases the rate of DMBA-induced rat mammary carcinoma, while a high dose decreased it. One of the most important factors determining the sensitivity to mammary carcinogenesis is the metabolic stage at administration of the carcinogenic agent. DMBA is a procarcinogen that recruits the host metabolism to yield its ultimate carcinogenic form, and CYP1A1 and CYP1B1 (CYP1) conduct this metabolism. We investigated the hepatic expression of CYP1 and AhR following oral administration of DMBA (100 mg/kg b.w.) (i.g.) to 50-day-old female Sprague-Dawley rats whose dams had been treated (i.g.) with 2.5 ng, 250 ng, 7.5 microg of PCB126/kg or the vehicle on days 13 to 19 post-conception. Real-time quantitative RT-PCR analysis revealed that the prenatal exposure to a relatively low dose of PCB126 (the 250 ng group) prolonged the higher expression of CYP1A1, CYP1B1, and AhR mRNA, while prenatal exposure to a high dose of PCB126 (the 7.5 microg group) prolonged the higher expression of CYP1A1 and AhR mRNA. Western blotting and immunohistochemical analyses were consistent with mRNAs changes. Because DMBA oxidation produces a highly mutagenic metabolite and is finally catalyzed by CYP1B1, a relatively low PCB126 dose might produce the biological character to potentially increase the risk of DMBA-induced mammary carcinoma.

Effect of mechanical compression on the lumbar nerve root: localization and changes of intraradicular inflammatory cytokines, nitric oxide, and cyclooxygenase.

STUDY DESIGN: Investigation of intraradicular inflammation induced by mechanical compression. OBJECTIVE: To investigate the mechanism of nerve root pain, this study used a lumbar nerve root compression model. SUMMARY OF BACKGROUND DATA: The manifestation of pain at sites of inflammation has a close relationship with the release of mediators from macrophages. However, the mediators involved in inflammation of nerve roots as a result of mechanical compression remain almost unknown. METHODS: In this study, the seventh lumbar nerve root of dogs was compressed with a clip for 3 weeks to observe the changes caused by compression. Immunohistochemistry was performed using the avidin-biotin-peroxidase complex method to observe the changes of T cells (CD45) and macrophages (Mac-1) after compression. Antibodies against as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (i-NOS), and cyclooxygenase (COX)-1 and 2 were used to examine the localization and changes of these mediators caused by nerve root compression. RESULTS: In control animals, resident T cells were detected, but there were no macrophages. IL-1beta and COX-2 were positive in the Schwann cells and vascular endothelial cells, while COX-1 was detected in the vascular endothelial cells. However, no cells showed TNF-alpha or i-NOS positively. After nerve root compression, numerous T cells and macrophages appeared among the demyelinized nerve fibers. The macrophages were positive for IL-1beta, TNF-alpha, i-NOS, and COX-2. CONCLUSION: Inflammatory cytokines, NO, and COX-2 may be deeply involved in radiculitis caused by mechanical compression, and these mediators seem to be important in the manifestation of root pain.

Effect of lactational exposure to tributyltin chloride on innate immunodefenses in the F1 generation in mice.

We examined the effect of lactational exposure to tributyltin on innate immunodefenses in the F1 generation using in vivo and in vitro experiments. Pregnant C57BL/6 mice were given drinking water containing 0, 15, or 50 microg/ml of tributyltin chloride (TBTCl) from parturition to weaning. At weaning time, offspring were inoculated with Escherichia coli K-12, and bacterial clearances from the peritoneal cavity and spleen were examined. In vivo infection experiments indicated that bacterial clearance was significantly depressed in offspring breast-fed by dams exposed to 15 microg/ml of TBTCl (15 ppm F1), but not in offspring by dams exposed to 50 microg/ml of TBTCl (50 ppm F1). In vitro functional assays revealed that the killing activity of neutrophils decreased significantly in 15 ppm F1, but not in 50 ppm F1. We suggest that lactational exposure to TBT impairs innate immunodefenses in the F1 generation against non-pathogenic bacterial infection.

CYP1 and AhR expression in 7,12-dimethylbenz[a]anthracene-induced mammary carcinoma of rats prenatally exposed to 3,3',4,4',5-pentachlorobiphenyl.

We previously reported the finding that prenatal exposure to a relatively low dose of 3,3',4,4',5-pentachlorobiphenyl (PCB126) acted as an enhancing agent for 17-beta-estradiol (E2)-dependent 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinoma, while a high dose decreased it. E2 is a known risk factor for mammary carcinoma, and CYP1A1 and 1B1 (CYP1) are the major enzymes catalyzing 2- and 4-hydroxylation of E2, respectively. We investigated the induction of CYP1 and aryl hydrocarbon receptor (AhR) in DMBA-induced mammary carcinoma using female Sprague-Dawley rats whose dams had been treated (i.g.) with 2.5 ng, 250 ng, 7.5 microg of PCB126/kg or the vehicle on days 13-19 post-conception. Immunohistochemical analysis revealed that the mammary carcinoma of the 250 ng group showed a significantly higher number of nuclei expressing estrogen receptor alpha (ER) and proliferating cell nuclear antigen (PCNA) compared to those of the other groups. Quantitative real-time RT-PCR analysis revealed that the 7.5 microg group showed a significantly higher level of CYP1A1 mRNA, and that the 250 ng group showed significantly higher levels of CYP1B1 mRNA. The level of AhR mRNA was significantly higher in both the 7.5 microg and 250 ng groups. Western blotting analysis was consistent with mRNA changes. It has been revealed that CYP1B1 catalyzes a step in the formation of 4-hydroxylated E2 metabolites, which show quite high mammary carcinogenicity. This study indicates that the enhancement of DMBA-induced mammary carcinogenicity in a relatively low PCB126 dose group might partially involve the higher expression of CYP1B1 and AhR in these carcinomas.

Na+,K+-ATPase activity is inhibited in cultured intestinal epithelial cells by endotoxin or nitric oxide.

Na+K+-ATPase is an important enzyme serving vital functions in various mammalian tissues, including the intestine. We have previously documented that endotoxin (LPS) and nitric oxide (NO) can induce enterocyte injury in vitro. To examine whether alterations Na+,K+-ATPase activity might be involved in LPS- or NO-induced enterocyte dysfunction, we carried out four series of experiments. The first set of experiments documented that LPS decreases IEC-6 Na+,K+-ATPase activity at concentrations as low as 0.10 microg/ml. The second set of experiments tested whether exposure of IEC-6 cells to the exogenous NO donor, S-Nitroso-N-acetylpenicillamine (SNAP), would decrease IEC-6 Na+,K+-ATPase activity. The results of these experiments documented that SNAP significantly decreased IEC-6 Na+,K+-ATPase activity in a dose-dependent fashion at a threshold inhibitory concentration of 0.1 mM, and there was an inverse correlation between Na+,K+-ATPase activity and NO concentrations in the medium. Since enterocytes contain iNOS, and LPS can increase iNOS activity, the third set of experiments examined the relationship between LPS-induced inhibition of Na+),K+-ATPase activity and NO production by the IEC-6 cells. These results showed that LPS increased IEC-6 NO production in both a dose- and time-dependent fashion and an inverse correlation existed between LPS-induced NO production and decreased Na+,K+-ATPase activity. Addition of the NOS inhibitor, L-NNA, prevented the LPS-induced decrease in Na+,K+ATPase activity, suggesting that NO is involved in the decrease of Na+,K+-ATPase activity observed in the IEC-6 cells incubated with LPS. One mechanism by which the increased NO concentrations could have contributed to the decrease in Na+,K+ATPase activity, after the addition of LPS or SNAP, is via the production of peroxynitrite during the reaction of NO with superoxide. This notion was supported by studies showing that SNAP- and LPS-induced decreases in IEC-6 Na+,K+-ATPase activity could be blocked by adding superoxide dismutase to the medium. The last set of experiments tested whether the inhibition of Na+,K+-ATPase activity with the specific Na+,K+-ATPase inhibitor ouabain would increase the permeability of an IEC-6 monolayer. IEC-6 monolayer permeability was increased by ouabain, but only at a high concentration. In conclusion, these studies indicate that LPS or the NO donor, SNAP, inhibit Na+,K+-ATPase activity and this inhibition is at least partly related to peroxynitrite production. These studies also suggest that LPS-induced NO production by the IEC-6 cells decreases IEC-6 Na+,K+-ATPase activity in an autocrine fashion.

Adrenomedullin as a sensitive marker for coronary and peripheral arterial complications in patients with atherosclerotic risks.

Plasma adrenomedullin (AM) levels are elevated in various pathological states including cardiovascular and inflammatory diseases. The present study investigated whether an increased AM level is a marker of vascular complications in patients with atherosclerotic risks. In 114 patients with cardiovascular risks and/or diseases including ischemic heart disease (IHD) and peripheral arterial disease (PAD), plasma AM concentration and other inflammatory markers such as high sensitive C-reactive protein (CRP) and interleukin (IL)-6 were examined. The plasma AM level was not altered by the absence or presence of each of four major risk factors, i.e., hypertension, diabetes mellitus, hyperlipidemia, and smoking and its level was not significantly correlated with blood pressure, plasma glucose, or serum lipid levels. The patients with IHD had a significantly higher concentration of plasma AM than those without IHD. The AM level in subjects with PAD was also increased significantly compared with those without PAD. The plasma AM was strongly correlated with inflammatory parameters such as CRP and IL-6. Among AM, CRP, and IL-6, however, only AM was an independent predictor for both IHD and PAD by multiple logistic regression analysis. Our findings suggest the possibility that plasma AM is a novel sensitive marker for the presence of vascular lesions in patients with atherosclerotic risks.

Lipoma and opthalmoplegia in mitochondrial diabetes associated with small heteroplasmy level of 3243 tRNA(Leu(UUR)) mutation.

We report a patient with mitochondrial diabetes mellitus associated with the A3243G mutation (MDM3243). The patient is a 77-year man with diabetes. At age 68, he noticed diplopia, due to superior rectus muscle palsy of the right eye. At age 70, he noticed lipoma on the right arm. The pathology of his muscle revealed some ragged-red fibers, and focal cytochrome c oxidase deficiency. Hence, he may have a pathogenetic mechanism in common with CPEO (chronic progressive external ophthalmoplegia) or mitochondria-related autoimmune disorder associated with mononeuropathy. He had the rate of 0.102% for heteroplasmy of 3243 mitochondrial DNA mutation in leukocytes. This case's heteroplasmy level is the smallest among the reported cases of MDM3243 in the literature. 3243 mitochondrial DNA mutation is known to induce a lack of uridine-modification in tRNA(Leu(UUR)) at the first letter of the anticodon, with which the third letter of the codon pairs, and decline of the pairing of the anticodon of tRNA with the codon of mRNA, suggesting the termination of polypeptide-elongation to generate premature proteins. Therefore, we speculate that these premature proteins may accumulate overtime, thereby affecting cells in target organs.

Plasma adrenomedullin concentration is increased in patients with peripheral arterial occlusive disease associated with vascular inflammation.

Adrenomedullin (AM), a potent vasodepressor, is known to have anti-atherosclerotic and anti-inflammatory effects. However, there is no information about its level in severe atherosclerotic diseases, such as peripheral arterial occlusive disease (PAOD). The present study investigated the plasma concentration of AM and several inflammatory parameters in 72 patients with and without PAOD. The plasma AM concentration in patients with PAOD was significantly higher than in those without PAOD. Its concentration had significant correlations with ankle-brachial index and Fontaine's stage. The plasma AM level also correlated with high sensitive C-reactive protein and interleukin-6. As an additional study, plasma levels of two forms of AM drawn from the femoral artery and saphenous vein were measured in 27 other subjects. Both mature and intermediate forms of plasma AM in the femoral artery and saphenous vein were higher in patients with PAOD than in those without PAOD. A significant step-up of the mature form of AM from the femoral artery to the saphenous vein was observed. Our findings indicate that the plasma AM concentration was elevated in patients with PAOD in proportion to the severity of the disease and associated with vascular inflammation. An increased production of AM in PAOD may play a protective role against advanced atherosclerosis with an inflammatory signature.

Changes in nerve root motion and intraradicular blood flow during intraoperative femoral nerve stretch test. Report of four cases.

OBJECT: It is not known whether changes in intraradicular blood flow (IRBF) occur during the femoral nerve stretch test (FNST) in patients with lumbar disc herniation. An FNST was conducted in patients with lumbar disc herniation to observe the changes in IRBF, and results were then compared with clinical features. METHODS: The study was composed of four patients with L3-4 disc herniation who underwent microdiscectomy. Patients were placed prone immediately before surgery, so that their knee flexed on the operating table with the hip joint kept in hyperextension, and the FNST was performed to confirm at which region pain developed in the anterolateral thigh. During the operation, the hernia-affected nerve roots were visualized under a microscope. The needle sensor of a laser Doppler flowmeter was then inserted into each nerve root immediately above the hernia, and the change in IRBF was measured during the intraoperative FNST. After removal of the herniated disc, a similar procedure was repeated and IRBF was measured again. The intraoperative FNST showed that the hernia compressed the nerve roots and there was marked disturbance of gliding, which was reduced to only a few millimeters. During the test, IRBF decreased by 92.8 to 100% (mean 96.9 +/- 3.7% [+/- standard error of the mean]) relative to the blood flow before the test. This study demonstrated that the blood flow in the nerve root is reduced when the nerve root is compressed in vivo. CONCLUSIONS: The intraoperative FNST showed that the hernia compressd the nerve roots and there was marked disturbance of gliding, which was reduced to only a few millimeters. During the test, IRBF decreased by 92.8 to 100% (96.9 +/- 3.7% [mean +/- standard error of the mean]).