Using Electrical Stimulation of the Ulnar Nerve Trunk to Predict Postoperative Improvement in Hand Clumsiness in Patients With Cervical Spondylotic Myelopathy.

STUDY DESIGN: A prospective cohort study. OBJECTIVE: To investigate whether the immediate and short-term effects of preoperative electrical peripheral nerve stimulation (ePNS) on performance of the 10-second test could predict the early postoperative outcomes of patients with cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: Previous studies have shown that early clinical improvement in CSM patients may be because of reversal of spinal cord ischemia after spinal cord compression. MATERIALS AND METHODS: We conducted a 10-second test before surgery, after ePNS, and at discharge (one week after surgery) in 44 patients with CSM who underwent C3-C7 laminoplasty and evaluated their correlations. The effects of the procedures (ePNS or operation) and sides (stimulated or nonstimulated side) for the 10-second test were analyzed using repeated measures analysis of variance. The Pearson correlation coefficient was used to measure the relationship between the 10-second test values according to the method (after ePNS vs. surgery). In addition, the Bland-Altman method was used to evaluate the degree of agreement between the 10-second test obtained after ePNS versus shortly after surgery. RESULTS: The preoperative 10-second test showed the most improvement immediately after the administration of ePNS, with a gradual decrease for the first 30 minutes after completion. After the initial 30 minutes, performance decreased rapidly, and by 60 minutes performance essentially returned to baseline. The 10-second post-ePNS had a strong positive correlation with the 10-second test in the early postoperative period (at discharge=one week after surgery). These phenomena were observed with the left hand, the side stimulated with ePNS, as well as the right hand, the side not stimulated. CONCLUSIONS: Early postoperative outcomes after CSM surgery may be predicted by the results of preoperative ePNS. LEVEL OF EVIDENCE: Level 3.

Effect of Early vs Delayed Surgical Treatment on Motor Recovery in Incomplete Cervical Spinal Cord Injury With Preexisting Cervical Stenosis: A Randomized Clinical Trial.

Importance: The optimal management for acute traumatic cervical spinal cord injury (SCI) is unknown. Objective: To determine whether early surgical decompression results in better motor recovery than delayed surgical treatment in patients with acute traumatic incomplete cervical SCI associated with preexisting canal stenosis but without bone injury. Design, Setting, and Participants: This multicenter randomized clinical trial was conducted in 43 tertiary referral centers in Japan from December 2011 through November 2019. Patients aged 20 to 79 years with motor-incomplete cervical SCI with preexisting canal stenosis (American Spinal Injury Association [ASIA] Impairment Scale C; without fracture or dislocation) were included. Data were analyzed from September to November 2020. Interventions: Patients were randomized to undergo surgical treatment within 24 hours after admission or delayed surgical treatment after at least 2 weeks of conservative treatment. Main Outcomes and Measures: The primary end points were improvement in the mean ASIA motor score, total score of the spinal cord independence measure, and the proportion of patients able to walk independently at 1 year after injury. Results: Among 72 randomized patients, 70 patients (mean [SD] age, 65.1 [9.4] years; age range, 41-79 years; 5 [7%] women and 65 [93%] men) were included in the full analysis population (37 patients assigned to early surgical treatment and 33 patients assigned to delayed surgical treatment). Of these, 56 patients (80%) had data available for at least 1 primary outcome at 1 year. There was no significant difference among primary end points for the early surgical treatment group compared with the delayed surgical treatment group (mean [SD] change in ASIA motor score, 53.7 [14.7] vs 48.5 [19.1]; difference, 5.2; 95% CI, -4.2 to 14.5; P = .27; mean [SD] SCIM total score, 77.9 [22.7] vs 71.3 [27.3]; P = .34; able to walk independently, 21 of 30 patients [70.0%] vs 16 of 26 patients [61.5%]; P = .51). A mixed-design analysis of variance revealed a significant difference in the mean change in ASIA motor scores between the groups (F1,49 = 4.80; P = .03). The early surgical treatment group, compared with the delayed surgical treatment group, had greater motor scores than the delayed surgical treatment group at 2 weeks (mean [SD] score, 34.2 [18.8] vs 18.9 [20.9]), 3 months (mean [SD] score, 49.1 [15.1] vs 37.2 [20.9]), and 6 months (mean [SD] score, 51.5 [13.9] vs 41.3 [23.4]) after injury. Adverse events were common in both groups (eg, worsening of paralysis, 6 patients vs 6 patients; death, 3 patients vs 3 patients). Conclusions and Relevance: These findings suggest that among patients with cervical SCI, early surgical treatment produced similar motor regain at 1 year after injury as delayed surgical treatment but showed accelerated recovery within the first 6 months. These exploratory results suggest that early surgical treatment leads to faster neurological recovery, which requires further validation. Trial Registration: ClinicalTrials.gov Identifier: NCT01485458; umin.ac.jp/ctr Identifier: UMIN000006780.

Development of a support tool for the clinical diagnosis of symptomatic lumbar intra- and/or extra-foraminal stenosis.

BACKGROUND: Not all lumbar intra- and/or extra-foraminal stenosis (LIEFS) on MRI is symptomatic. Therefore, the establishment of clinical diagnostic tools that can identify patients with symptomatic LIEFS is crucial in the clinical setting. The aim of this study was to develop a support tool for clinical diagnosis of LIEFS. METHODS: Patients with L5 radiculopathy alone were prospectively enrolled. Fifty-one patients with lumbar spinal canal stenosis only at the L4-5 level and 49 patients with LIEFS only at the L5-S1 level were extracted from this cohort. We compared the two groups with regard to 12 variables--three subjective and three objective items from the Japanese Orthopaedic Association (JOA) score; Kemp's sign; results of the lumbar flexion test, Bonnet test, and Freiberg test; pain on sitting; and pain when recumbent--to determine which factors were associated with a high index of clinical suspicion of LIEFS. RESULTS: The significant predictors of a final diagnosis of LIEFS were identified as follows: pain when recumbent, Freiberg and Bonnet test results, and pain on sitting. To develop a diagnostic tool, a scoring system (0-20 points) was formulated on the basis of the contribution ratios of these risk factors. To determine the contribution ratio, an integer score was assigned to the identified risk factors as follows: pain when recumbent = 9 points, Freiberg = 5 points, Bonnet = 3 points, and pain on sitting = 3 points. The Hosmer-Lemeshow statistic for this scoring system was p = 0.063, and confirmed that it was a good model. Receiver operating characteristic (ROC) curve analysis demonstrated a cut-off value of 5 points, an area under the ROC curve of 0.87435, sensitivity of 75.5 %, and specificity of 82.3 %. CONCLUSIONS: We believe that the use of this tool in the clinical setting will improve the accuracy of diagnosing symptomatic LIEFS, which will lead to improved quality of patient care.

Improved accuracy of diagnosis of lumbar intra and/or extra-foraminal stenosis by use of three-dimensional MR imaging: comparison with conventional MR imaging.

BACKGROUND: The purposes of this study were to assess the reliability of 3-dimensional magnetic resonance (MR) imaging (3D MRI) and conventional MRI (CMRI) for detection of lumbar intra and/or extra-foraminal stenosis (LIEFS) and to compare the diagnostic accuracy of the 2 imaging modalities. METHODS: A total of 60 sets of 3D MR and CMR images from 20 healthy volunteers and 40 LIEFS patients were qualitatively rated according to defined criteria by 3 independent, blinded readers. Kappa statistics were used to characterize intra and inter-reader reliability for qualitative rating of data. Multireader, multicase analysis was used to compare lumbar foraminal stenosis detection between the 2 modalities. RESULTS: Intra-reader agreement for 3D MRI was excellent, with kappa = 0.90; that for CMRI was good, with kappa = 0.78. Average inter-reader agreement for 3D MRI was good, with kappa = 0.79, whereas that for CMRI was moderate, with kappa = 0.41. Average area under the ROC curve values (1st reading/2nd reading) for detection of lumbar foraminal stenosis using 3D MRI and CMRI were 0.99/0.99 and 0.94/0.92, respectively. Detection of LIEFS with 3D MRI was significantly better than with CMRI (P = 0.0408/0.0294). CONCLUSIONS: These results suggest that CMRI was of limited use for detection of the presence of LIEFS. Isolated imaging with CMRI may risk overlooking the presence of LIEFS. In contrast, reliability of 3D MRI for detection of LIEFS was good. Furthermore, readers' performance in the diagnosis of LIEFS can be improved by use of 3D MRI. Therefore, 3D MRI is recommended when using imaging for diagnosis of LIEFS.

Exploring the thermochromism of sulfite-embedded polyoxometalate capsules.

The Dawson-type polyanion [α-Mo(18)O(54)(SO(3))(2)](4-), with two SO(3)(2-) templates embedded inside a polyoxomolybdate(vi) cage, exhibits thermochromism over an exceptionally wide temperature range (∼500 K). The temperature dependence of the cluster structure, established from X-ray crystallography, IR and Raman spectroscopy and DFT calculations, is related to a decreasing HOMO-LUMO gap in the near UV with increasing temperature. We postulate this is due to geometrical changes that affect both the occupied and unoccupied frontier molecular orbitals of this cluster anion.

Supramolecular cations of the m-fluoroanilinium(dibenzo[18]crown-6) in ferromagnetic salt.

A supramolecular cation of (m-FAni(+))(DB[18]crown-6), where m-FAni(+) and DB[18]crown-6 denote m-fluoroanilinium(+) and dibenzo[18]crown-6, respectively, which is the polar unit rotating in the ferroelectric crystal of (m-FAni(+))(DB[18]crown-6)[Ni(dmit)(2)](-), was introduced into a ferromagnetic [MnCr(oxalate)(3)](-) salt as the counter cation. The crystal structure of (m-FAni(+))(DB[18]crown-6)[MnCr(oxalate)(3)](-)(CH(3)OH)(CH(3)CN) (1) is constructed from alternating layers of a two-dimensional honeycomb layer of [MnCr(oxalate)(3)](-) and (m-FAni(+))(DB[18]crown-6) supramolecular cations. The anionic layer is composed of Mn(II) and Cr(III) ions with S = 5/2 and S = 3/2 spins, respectively, bridged by the oxalate anions, which show ferromagnetic ordering at 5.5 K. The supramolecular structure is formed through the formation of hydrogen bonds between the ammonium hydrogen atoms of the m-FAni(+) cations and the oxygen atoms of the DB[18]crown-6 cavity. No orientational disorder of the fluorine atoms was observed in our X-ray structural analysis, suggesting that a two-fold flip-flop motion of the m-FAni(+) cations does not occur in the salt. The rotational freedom of the m-FAni(+) cations in the salt is restricted by the steric hindrance from neighbouring DB[18]crown-6 molecules. A design strategy for the rotation in a salt is discussed, based on the volume that the supramolecular cations occupy in the unit cell.

[18]Crown-6 rotator in spin-ladder compound of m-aminoanilinium([18]crown-6)[Ni(dmit)2]-.

Supramolecular cations of HOPD+([18]crown-6) and HMPD+([18]crown-6) were introduced into [Ni(dmit)2]- salts (HOPD+: o-aminoanilinium, HMPD+: m-aminoanilinium, and dmit2-: 2-thioxo-1,3-dithiole-4,5-dithiolate). Alternate layers of cations and anions were observed in the two new salts of (HOPD+)([18]crown-6)[Ni(dmit)2]- (1) and (HMPD+)([18]crown-6)[Ni(dmit)2]- (2). From X-ray crystal structural analyses, solid state 1H nuclear magnetic resonance (NMR) spectra, and dielectric constants, the thermal rotations of [18]crown-6 in both of the (HOPD+)([18]crown-6) and (HMPD+)([18]crown-6) supramolecules occurred at temperatures above approximately 200 K based on the orientational disorder in the crystal structures. The two-fold flip-flop motions of HOPD+ and HMPD+ cations in salts 1 and 2 were suppressed, due to the relatively large potential energy barriers. The [Ni(dmit)2]- anion formed pi-dimer arrangements in both salts, with a layer structure by lateral sulfur-sulfur interatomic contacts. Although the simple dimer model reproduced the magnetic properties of salt 1, the ladder arrangement of the pi-dimer in salt 2 yielded the magnetic behavior of a spin-ladder with a spin-gap of 92.5 K. The temperature dependent magnetic susceptibility of salt 2 was well reproduced by the magnetic anisotropy of J1/J2 approximately = 8 between the ladder-leg (J1: intra-dimer interaction) and ladder-rung (J2: inter-dimer interaction). The [18]crown-6 supramolecular rotator of (HMPD+)([18]crown-6) was coexistent with the spin-ladder chain of [Ni(dmit)2]- anions in salt 2.

Asymmetrical [Ni(dmit)2]- arrangements induced by (1R,2R)-cyclohexanediammonium-crown ether supramolecules.

Structurally flexible (1R,2R)-cyclohexanediammonium (CHDA(2+)) dication formed hydrogen-bonding supramolecules with [18]crown-6, benzo[18]crown-6 (B[18]crown-6), dibenzo[18]crown-6 (DB[18]crown-6), and dicyclohexano[18]crown-6 (DCH[18]crown-6) in [Ni(dmit)(2)](-) salts (dmit(2-) = 2-thioxo-1,3-dithiole-4,5-dithiolate). The two ammonium moieties of CHDA(2+) interacted with the crown ethers to form open-mouth-shaped sandwich-type cationic structures of (CHDA(2+))(crown ethers)(2), that is, (CHDA(2+))([18]crown-6)(2)[Ni(dmit)(2)](2)(-)() (1), (CHDA(2+))(B[18]crown-6)(2)[Ni(dmit)(2)](2)(-)() (2), (CHDA(2+))(DB[18]crown-6)(2)[Ni(dmit)(2)](2)(-)() (3), and (CHDA(2+))(DCH[18]crown-6)(2)[Ni(dmit)(2)](2)(-)() (4). The chiral structure of CHDA(2+) induced asymmetrical [Ni(dmit)(2)](-) arrangements in the crystals. A large frequency and temperature dependence of the dielectric response was observed in (CHDA(2+))(B[18]crown-6)(2), due to the pendulum motion of the cyclohexane ring along the nitrogen-nitrogen direction of CHDA(2+). Since the inversion center of the [Ni(dmit)(2)](-) arrangements was lost in the unit cell due to the chiral space group, the salts 1-4 showed rather complicated magnetic behaviors. The temperature-dependent magnetic properties of salts 3 and 4 were explained by the sum of the Curie-Weiss and singlet-triplet thermal excitation models, with positive (ferromagnetic) and negative (antiferromagnetic) magnetic exchange energies, respectively.

A prospective randomized study of clinical outcomes in patients with cervical compressive myelopathy treated with open-door or French-door laminoplasty.

STUDY DESIGN: A prospective randomized clinical study. OBJECTIVE: To compare the clinical outcomes of open-door and French-door laminoplasties. SUMMARY OF BACKGROUND DATA: Expansive laminoplasty for cervical compressive myelopathy is well established and a variety of modifications procedures have been developed. The procedures are mainly classified into open-door and French-door. It has never been prospectively investigated as to which surgical procedure, open-door or French-door laminoplasty, results in a more favorable outcome. METHODS: After informed consent was obtained from 40 patients, they were randomized into 2 surgical groups A and B. Patients in group A had open-door laminoplasty, and patients in group B underwent French-door laminoplasty with reattachment of the spinous process and extensor musculatures. The following criteria were evaluated: operation time, blood loss, perioperative complications, Japanese Orthopedic Association (JOA) scores, recovery rates, axial pain, and short-form 36 (SF-36). For radiographic evaluation, cervical lordosis was reviewed as lordotic angles, which were measured at C2-C7. RESULTS: Although the operation time was significantly less in group A as compared with group B, the mean blood loss in group A was significantly more than group B. Perioperative complications occurred more frequently in group A than in group B. Although there were no significant differences in postoperative JOA scores and recovery rates between the 2 groups, axial pain was significantly decreased in group B at final follow-up. The scores of every subscale of the SF-36 were higher in group B than group A. CONCLUSION: Perioperative complications occurred more frequently in open-door laminoplasty than in French-door laminoplasty. JOA scores and recovery rates suggested that both open-door and French-door laminoplasties could be similarly effective in decompressing the spinal cord. Axial pain was improved in French-door laminoplasty but became worse in open-door laminoplasty. SF-36 suggested that French-door laminoplasty could be more beneficial than open-door laminoplasty for patients with cervical compressive myelopathy.

[Serotonin and anticancer drug-induced emesis].

Cytotoxic drug-induced nausea and vomiting are the side effects most feared by cancer patients. Emesis is an instinctive defense reaction caused by the somato-autonomic nerve reflex, which is integrated in the medulla oblongata. Emesis caused by anticancer drugs is associated with an increase in the concentration of serotonin (5-HT) (5-HT) in the intestinal mucosa and brainstem. 5-HT released from the enterochromaffin (EC) cells, which synthesize and secrete 5-HT, stimulates the 5-HT receptors on the adjacent vagal afferent nerves. The depolarization of the vagal afferent nerves stimulates the vomiting center in the brainstem and eventually induces a vomiting reflex. 5-HT released from EC cells appears to mediate the cisplatin-induced emesis sensitive to 5-HT(3) receptor antagonists. The precise role of 5-HT in the occurrence of vomiting has not been fully elucidated. The present review describes the role of 5-HT in anticancer drug-induced emesis from the viewpoint of 5-HT release and afferent vagal nerve activity. Various models and methods for predicting emesis are also evaluated.

Pharmacological aspects of anticancer drug-induced emesis with emphasis on serotonin release and vagal nerve activity.

Cytotoxic drug-induced nausea and vomiting are the side effects most feared by cancer patients. Emesis is an instinctive defense reaction caused by the somatoautonomic nerve reflex, which is integrated in the medulla oblongata. Emesis caused by cytotoxic drugs such as cisplatin is associated with an increase in the concentration of 5-hydroxytryptamine (5-HT) in the intestine and the brainstem. It is proposed that cytotoxic drugs evoke 5-HT release from the enterochromaffin (EC) cells in the intestinal mucosa and that the released 5-HT stimulates the 5-HT receptors on the adjacent vagal afferent nerves. The depolarization of the vagal afferent nerves stimulates the vomiting center in the brainstem and eventually induces a vomiting reflex. 5-HT released from EC cells seems to mediate the cisplatin-induced emesis sensitive to 5-HT(3) receptor antagonists. The release of 5-HT from the EC cells, however, is regulated by polymodal mechanisms on autoreceptors or heteroreceptors. The precise role of 5-HT on the occurrence of vomiting has not been fully elucidated. The present review aims to describe the role of 5-HT in anticancer drug-induced emesis from the viewpoint of 5-HT release and afferent vagus nerve activity. Various methods for predicting emesis are also evaluated.

5-hydroxytryptamine (5-HT) concentrations in the hippocampus, the hypothalamus and the medulla oblongata related to cisplatin-induced pica of rats.

We previously reported that the concentration of 5-hydroxytryptamine (5-HT) in the brainstem of cisplatin-administered ferrets is significantly increased as compared with that of control animals. In an attempt to clarify the mechanisms of emesis induced by cytotoxic drugs, we measured kaolin ingestion (pica) and the tissue concentrations of 5-HT, norepinephrine (NE) and dopamine in various brain regions of rats after cisplatin administration. 5-HT concentrations in the hippocampus, the medulla oblongata and the hypothalamus significantly increased 72 hours after a single dose administration of cisplatin (5 mg/kg, i.p.) compared with those of control rats. NE concentration in the hippocampus significantly increased simultaneously with kaolin ingestion in cisplatin-treated rats. These results suggest that higher brain regions such as the hippocampus and the hypothalamus are involved in cisplatin-induced emesis.

Effects of fluvoxamine, a selective serotonin re-uptake inhibitor, on serotonin release from the mouse isolated ileum.

The presence of nausea and vomiting is problematic for all selective serotonin re-uptake inhibitors (SSRIs), and their usefulness as anti-depressants is limited in this respect. In an attempt to examine the background of SSRI-induced emesis, the present study aims to describe the role of 5-hydroxytryptamine (serotonin:5-HT) from the viewpoint of 5-HT release in the mouse-isolated ileum. In this study, it was demonstrated that 5-HT release from the mouse-isolated ileum was significantly increased by fluvoxamine at a concentration of 10(-6) M. Also, it was demonstrated that granisetron, a 5-HT3 receptor antagonist, inhibited significantly the increase in fluvoxamine (10(-6) M) -induced 5-HT release. The effect of granisetron on fluvoxamine-induced 5-HT release was occurred in a concentration-dependent manner. The present study demonstrated for the first time that the SSRI-induced increase in 5-HT release from the isolated ileum was significantly inhibited by 5-HT3 receptor antagonist. These results suggest that 5-HT3 receptors might be involved in SSRI-induced 5-HT release from the mouse isolated ileal tissue. Fluvoxamine (10(-6) M)-induced 5-HT release was inhibited concentration -dependently by the concomitant perfusion of diltiazem. The results suggest that L-type calcium channel might be also involved in SSRI-induced 5-HT release from the isolated ileum. Furthermore, tetrodotoxin (10(-6) M) completely inhibited the increase in 5-HT release induced by fluvoxamine. This finding suggests that the increase of 5-HT induced by fluvoxamine involves enterochromaffin (EC) cell stimulation via an inter-neuron pathway in the gastrointestinal tract (GI). SSRI initiates an increase in the concentration of 5-HT in the GI tract. 5-HT released from the EC cells of the intestinal mucosa may stimulate the 5-HT3 receptors on vagal afferent nerve fibers. This depolarization of vagal afferents may result in a 5-HT increase in the brainstem and, thus, lead to emesis.

[Clinical study of the combination of small amount of nedaplatin (CDGP)/5-FU with radiation for the treatment of esophageal cancer].

Recently chemoradiotherapy for esophageal cancer has been drawing public attention to the issue of quality of life maintenance for patients. Although the standard method of chemoradiotherapy is CDDP/5FU, it has been claimed that CDGP (a derivative of CDDP) alone is more effective than CDDP for the treatment of esophageal cancer due to its low nephro- and digestive toxicity. We used a small amount of CDGP/5-FU in combination with radiation instead of CDDP, for the treatment of esophageal cancer and performed clinical examination of patients. The partial response rate was 80% and the complete response rate was 50%. Major side-effects were leukopenia, neutropenia, thrombocytopenia and anemia. Further study of dosage and schedule is necessary, however, CDGP/5-FU combined with radiation therapy could be used as choices of chemoradiotherapy for esophageal cancer in the future.

Reduced expressions of inducible nitric oxide synthase and cyclooxygenase-2 in vascular smooth muscle cells of stroke-prone spontaneously hypertensive rats.

Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 are expressed in vascular smooth muscle cells stimulated with interleukin-1beta (IL-1beta), resulting in the production of nitric oxide (NO) and prostaglandins (PGs) such as PGI2. The iNOS and COX-2 proteins and their mRNA expressions in cultured vascular smooth muscle cells isolated from 6-7 week-old stroke-prone spontaneously hypertensive rats (SHRSP) were compared with those in the cells isolated from age-matched normotensive Wistar Kyoto rats (WKY). The IL-1beta-induced NO production and iNOS expression in vascular smooth muscle cells of SHRSP were significantly lower than those in cells of WKY. Similarly, PGI2 production and COX-2 expression were significantly lower in vascular smooth muscle cells of SHRSP than WKY, whereas there was no difference in the COX-1 expression. There were no significant differences in iNOS and COX-2 mRNA expressions between the two strains, suggesting that these protein expression may be reduced at the post-transcriptional level in cells of SHRSP. These results further suggest that the reduction of iNOS and COX-2 expressions in vascular smooth muscle cells may have relevance to the pathophysiology in SHRSP.

Effects of granisetron, a 5-HT3 receptor antagonist, on 5-hydroxytryptamine (5-HT) release from the isolated ileum in a delayed-emesis rat model.

We examined the effects of granisetron, a 5-HT3-receptor antagonist, on the release of serotonin (5-hydroxytryptamine, 5-HT) from the isolated ileum and on histopathological changes of the intestine in a delayed-emesis rat model. The rats were studied 72 hours after receiving an intraperitoneal (i.p.) dose of cisplatin (5 mg/kg). The 5-HT content in the isolated ileum 72 hours after administration was significantly higher in the cisplatin group (26.0 +/- 3.0 ng/mg protein, p < 0.001) than in the non-drug control group (9.6 +/- 0.6 ng/mg protein). The increase in 5-HT content in the cisplatin group was significantly inhibited in rats pretreated with granisetron (17.5 +/- 2.2 ng/mg protein, p < 0.05). The release of 5-HT from the isolated ileum was significantly greater in the cisplatin group (11,963.0 +/- 2,104.6 ng x hr/g tissue, p < 0.01) than in the non-drug control group (2,861.0 +/- 210.7 ng x hr/g tissue). The increased 5-HT release from the isolated ileum in the cisplatin group was significantly inhibited in rats pretreated with granisetron (3,359.8 +/- 494.3 ng x hr/g tissue, p < 0.01). Disarrangement of intestinal villi, luminal dilatation of crypts and decreased numbers of goblet cells were observed in the cisplatin group. The group pretreated with granisetron showed mild macroscopic and histopathological changes, but no significant weight loss. The histopathological changes of the intestinal mucosa were apparently associated with the release of 5-HT. Our results suggest that 5-HT release from the enterochromaffin cells, accompanied by histopathological changes of the intestinal mucosa, is involved in the onset of delayed emesis after administration of cisplatin. These findings suggest that treatment with granisetron before the administration of anticancer drugs may prevent delayed emesis and intestinal disturbances associated with anticancer drugs.