Biomedical subjects

M Fujii

Publications and source records attributed to M Fujii.

At least 55 records · Page 3Linked to original sources

PubMed2001

Relationship between plasma level of cardiotrophin-1 and left ventricular mass index in patients with dilated cardiomyopathy.

OBJECTIVES: The study evaluated the relationship between plasma cardiotrophin-1 (CT-1) concentration and left ventricular (LV) mass in dilated cardiomyopathy (DCM) patients with congestive heart failure (CHF). BACKGROUND: Cardiotrophin-1 is a newly identified member of the interleukin-6 (IL-6) family of cytokines and one of the endogenous ligands for gp130 signaling pathways in the heart, and it has potent hypertrophic and survival effects on cardiac myocytes. However, the clinical significance of CT-1 is poorly understood. METHODS: We measured the plasma CT-1 level in 51 consecutive patients with DCM. Patients were classified into two groups: small LV mass index group and large LV mass index group, based on the median level of LV mass index. RESULTS: The plasma CT-1 level was increased in DCM patients with the severity of CHF and was significantly higher in the large LV mass group than in the small LV mass group, despite the absence of a difference in LV ejection fraction between the two groups. In addition, there was a significant positive correlation between the plasma CT-1 level and the LV mass index (r = 0.627, p < 0.0001). According to stepwise multivariate analyses among hemodynamic and neurohumoral factors, a high plasma CT-1 level showed an independent and significant positive relationship with a large LV mass index in patients with DCM. CONCLUSIONS: These results indicate that the plasma CT-1 level is increased in patients with DCM and is significantly correlated with the LV mass index, suggesting that CT-1 plays an important role in structural LV remodeling in patients with DCM.

Adolescent↗

PubMed2001

Cyclin D1 amplification correlates with early recurrence of squamous cell carcinoma of the tongue.

Amplification of CCND1 was studied in 23 tongue carcinoma patients by fluorescence in situ hybridization (FISH) using a paraffin embedded specimen. All the patients received complete resection of the primary site with or without neck dissection. CCND1 amplification was positive in 13 (56.5%) out of 23 cases. Correlations between CCND1 amplification and histological grading, T category, N category, and Stages were not significant. The 5-year disease-free survival rate, which was 23.1% for CCND1 amplification positive patients and 80.0% for negative patients, was significantly better for the CCND1 amplification negative patients (P=0.0070). Nine patients were examined by dual-color FISH with the probe for centromere of chromosome 11 and 11q13. In five patients, who had positive amplification for CCND1, cell numbers with a larger number of signals for 11q13 than the centromere of chromosome 11 were significantly higher than those of CCND1 amplification negative patients (P=0.013). This indicates that amplification of 11q13 occurs more frequently than aberration of chromosome 11 in CCND1 amplification positive patients. From these results, the amplification of CCND1 is a key factor in predicting the aggressiveness of tongue cancer. Furthermore, FISH proved to be a useful method for such evaluation.

Carcinoma, Squamous Cell↗

PubMed2001

Ectopic expression of Smad7 inhibits transforming growth factor-beta responses in vascular smooth muscle cells.

Vascular injury stimulates the cytokine-growth factor network in the vascular wall, including transforming growth factor-beta (TGF-beta). Reportedly, the intracellular signaling of TGF-beta is mediated by Smad proteins. We tested the effects of the ectopic expression of inhibitory Smads in cultured rat smooth muscle cells (SMC) to identify the role of TGF-beta/Smad signaling on the phenotypic modulation of SMC. The cells exposed to human recombinant TGF-beta1 (10 ng/ml) were stimulated Smad2 phosphorylation. Infection with the replication-deficient adenovirus vector expressing Smad7, but not bacterial beta-galactosidase or Smad6, was found to inhibit TGF-beta-induced Smad2 phosphorylation in a dose-dependent manner. TGF-beta suppressed the serum-induced proliferation of SMC from 36.3% to 51.0% (p<0.01), as measured by hand-counting, and this inhibition was attenuated by the ectopic expression of Smad7 (from 30.7% to 74.8% of the reduction of TGF-beta-response, p<0.05), but not Smad6. A BrdU incorporation assay also showed that TGF-beta-mediated growth inhibition was attenuated by exogenous Smad7 and that this inhibition can be reversed by an additional expression of exogenous Smad2. TGF-beta increased the expression of alpha-smooth muscle actin and myosin heavy chain by 1.3-fold and 1.6-fold in comparison to the control, respectively, and these increases were attenuated by exogenous Smad7, but not Smad6. Our data indicate that Smads mediate TGF-beta responses on SMC phenotypes. Smad7, but not Smad6, may specifically act as an inhibitor of TGF-beta responses.

Animals↗

PubMed2001

Endothelin-1 promotes vascular structural remodeling during the progression of heart failure prevention of vascular remodeling using a specific endothelin-converting enzyme inhibitor.

To evaluate the effects of endothelin (ET)-converting enzyme (ECE) inhibitor on vascular remodeling in dogs with congestive heart failure (CHF), we chronically administered an ECE inhibitor, FR901533 (FR, iv. 0.3mg/kg/hr, n=6), to dogs with CHF induced by rapid ventricular pacing. Vehicle CHF dogs were given saline (n=7). In the vehicle CHF group after 3 weeks of pacing, the ET system was activated in the plasma and vasculature (3 and 5 times higher than normal, respectively). Inward remodeling occurred in the femoral artery; medial thickness (MT, 225+/-5 vs 193+/-4 microm, P<0.05) and deposition of collagen (DC, 22+/-2 vs 17+/-1%, P<0.01) significantly increased, while lumen diameter (LD, 1173+/-39 vs 1481+/-44 microm, P<0.05) decreased in the femoral artery with CHF compared with the normal femoral artery. There were significant correlations between the number of ET-1 positive cells and MT, DC, LD and systemic vascular resistance. FR significantly suppressed the changes in these vascular parameters compared with the changes in the vehicle CHF group despite the lack of an effect on blood pressure, and moreover FR caused decreases in ET-1 levels in both the plasma and femoral artery (reduced to 43% and 54%, respectively, of the levels in the vehicle CHF group, P<0.05). In conclusion, ET-1 plays a critical role in the structural deterioration of the vasculature during the progression of CHF, and ECE inhibitors can prevent the development of vascular remodeling.

Animals↗

PubMed2001

Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies.

OBJECTIVE: To characterize the specificity of anti-GAD(65) antibodies in patients with stiff person syndrome (SPS), quantify antibody titers, and examine antibody production within the CNS. METHODS: The authors studied 18 patients with SPS and positive serum immunoreactivity to gamma-aminobutyric acid (GABA)-ergic neurons. The reactivity of serum and CSF to purified GAD antigen was examined by Western blots, and the anti-GAD(65) antibody titers in serum and CSF were quantified by ELISA and compared with 70 disease controls (49 with other autoimmune disorders and 11 with insulin-dependent diabetes mellitus). The intrathecal synthesis of anti-GAD(65) IgG was calculated, and the functional significance of the antibodies was examined by measuring the GABA levels in the CSF. RESULTS: The serum and CSF of all selected patients with SPS had high anti-GAD(65) titers (from 7.0 to 215 microg/mL in serum and from 92 to 2500 ng/mL in CSF) and immunoreacted strongly with recombinant GAD(65) on Western blots and with GABA-ergic neurons on rat cerebellum. Among controls, only the serum of eight patients with insulin-dependent diabetes mellitus had low anti-GAD(65) antibody titers (from 200 to 1760 ng/mL) but no reactivity to recombinant GAD(65). The CSF showed oligoclonal IgG bands in 10 (67%) of 15 patients and an increased anti-GAD(65)-specific IgG index in 11 (85%) of 13. The mean level of GABA in the CSF was lower in patients with SPS than in controls. CONCLUSIONS: In patients with SPS, there is marked intrathecal antibody response against neuronal GAD(65) epitopes, indicating a clonal B cell activation in the CNS. Anti-GAD(65) antibodies at high titers, when confirmed with immunoblots, are highly specific for SPS and appear to impair GABA synthesis.

Animals↗

PubMed2001

Ameliorative effect of vasopressin-(4-9) through vasopressin V(1A) receptor on scopolamine-induced impairments of rat spatial memory in the eight-arm radial maze.

In order to clarify the mechanism by which pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH(2) (vasopressin-(4-9)), a major metabolite C-terminal fragment of [Arg(8)]-vasopressin (vasopressin-(1-9)), improves learning and memory, we used several different drugs such as an acetylcholine receptor antagonist, a Ca(2+)/calmodulin-dependent protein kinase II inhibitor, vasopressin receptor antagonists and L-type Ca(2+) channel blocker to disrupt spatial memory in rats. Moreover, we examined the effect of vasopressin-(4-9) on acetylcholine release in the ventral hippocampus using microdialysis. Vasopressin-(4-9) (10 fg/brain, i.c.v.) improved the impairment of spatial memory in the eight-arm radial maze induced by scopolamine, pirenzepine and Ca(2+)/calmodulin -dependent protein kinase II inhibitor. Pirenzepine, a vasopressin V(1A) receptor antagonist, and L-type Ca(2+) channel blocker, but not a vasopressin V(2) receptor antagonist, suppressed the effects of vasopressin-(4-9) on scopolamine-induced impairment of spatial memory. Moreover, vasopressin-(4-9) did not affect acetylcholine release in the ventral hippocampus of intact rats or of scopolamine-treated rats as assessed by microdialysis. These results suggest that vasopressin-(4-9) activates vasopressin V(1A) receptors on the postsynaptic membrane of cholinergic neurons, and induces a transient influx of intracellular Ca(2+) through L-type Ca(2+) channels to interact with muscarinic M(1) receptors. The activation of these processes by vasopressin-(4-9) is critically involved in the positive effect of vasopressin-(4-9) on scopolamine-induced impairment of spatial memory.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2001

Effect of phosphatidylcholine on skin permeation of indomethacin from gel prepared with liquid paraffin and hydrogenated phospholipid.

The effects of hydrogenated and unhydrogenated phosphatidylcholine (HPC, PC) on the permeation of indomethacin (IM) through hairless rat skin were investigated using liquid paraffin (LP) and a gel prepared with LP and hydrogenated soybean phospholipid (HSL). IM solubility at 95 degrees C increased in proportion to the concentration of HPC or PC, whereas solubility at 37 degrees C did not increase with HPC. IM showed no permeation until 10 h from LP without HPC/PC, but permeated at rates of approximately 5 and 10 microg/cm2 within 10 h from LP with HPC and PC, respectively. The permeation from the gel with various formulations (HSL, 15%; PC/HPC, 0-5%; IM, 0.5-2%) was determined. Permeation rates were 1.7-4.8 microg/cm2 per h and were proportional to the skin concentration. Skin concentration was correlated to the release rate from the gel. We concluded that IM was solubilized by phospholipids, high activity in the vehicle led to high partition of IM in skin, and permeation increased due to a high skin concentration.

Animals↗

PubMed2001

Relationship between tumor necrosis factor-alpha production and oxidative stress in the failing hearts of patients with dilated cardiomyopathy.

OBJECTIVES: This study evaluated oxidative stress in the failing ventricle in patients with dilated cardiomyopathy (DCM). BACKGROUND: Oxidative stress appears to increase in the failing myocardium and may contribute to ventricular dysfunction in patients with DCM. Tumor necrosis factor-alpha (TNF-alpha), which is expressed in the failing heart, may stimulate oxidative stress. METHODS: We measured plasma oxidized low density lipoprotein (oxLDL) by sandwich enzyme-linked immunosorbent assay using specific antibodies against oxLDL in the aortic root (AO) and the coronary sinus (CS) in control subjects (n = 8) and in 22 patients with DCM and mild congestive heart failure. We also measured the plasma levels of TNF-alpha and angiotensin II. RESULTS: There was no difference in oxLDL between the AO and CS in control subjects. In contrast, plasma oxLDL was significantly higher in the CS than the AO in patients with DCM, suggesting that the transcardiac gradient ofoxLDL reflects oxidative stress in the failing heart in these patients. Plasma TNF-alpha levels were significantly higher in the CS than the AO with a significant positive correlation of the transcardiac gradient of TNF-alpha and the transcardiac gradient of oxLDL. Moreover, a significant negative correlation existed between the transcardiac gradient of oxLDL and left ventricular ejection fraction. The transcardiac gradient of plasma oxLDL was significantly lower in 6 patients who received carvedilol than in 16 patients who did not receive carvedilol. CONCLUSIONS: These findings indicate that the transcardiac gradient of oxLDL may be a marker of oxidative stress in the heart and that left ventricular dysfunction may be partly due to the oxidative stress in patients with DCM. In addition, TNF-alpha may stimulate oxidative stress in the failing heart in patients with DCM.

Adolescent↗

PubMed2001

5-Bromodeoxyuridine suppresses position effect variegation of transgenes in HeLa cells.

An ectopic gene integrated in the host genome is occasionally silenced due to a position effect of its adjacent chromatin structure. We found that 5-bromodeoxyuridine clearly activated such a transgene in HeLa cells. The transgene was also activated to various degrees by inhibitors of histone deacetylase, DNA topoisomerases, or DNA methyltransferase. The peptide antibiotic distamycin A potentiated markedly the effect of 5-bromodeoxyuridine. Transient expression of an artificial AT-hook protein termed MATH20 also potentiated its effect although significantly activated the transgene alone. Since distamycin A and MATH20 are able to displace histone H1 and other DNA-binding proteins bound to specific AT-rich sequences by a dominant, mutually exclusive fashion, these results suggest that 5-bromodeoxyuridine targets such an AT-rich sequence located adjacent to the silenced transgene, resulting in chromatin accessibility.

Antimetabolites, Antineoplastic↗

PubMed2001

Aminopeptidase from Sphingomonas capsulata.

A novel aminopeptidase with unique substrate specificity was purified from a culture broth of Sphingomonas capsulata. This is the first reported aminopeptidase to demonstrate broad substrate specificity and yet release glycine and alanine with the highest efficacy. On a series of pentapeptide amides with different N-terminal amino acids, this enzyme efficiently releases glycine, alanine, leucine, proline, and glutamate with the lowest turnover value of 370 min(-1) for glutamate. At pH 7.5 (pH optimum) and 25 degrees C, the kinetic parameters for alanine para-nitroanilide were found to be k(cat) = 7600 min(-1) and K(m) = 14 mm. For alanine beta-naphthylamide, they were k(cat) = 860 min(-1) and K(m) = 6.7 mm. Polymerase chain reaction primers were designed based upon obtained internal sequences of the wild type enzyme. The subsequent product was then used to acquire the full-length gene from an S. capsulata genomic library. An open reading frame encoding a protein of 670 amino acids was obtained. The translated protein has a putative signal peptide that directs the enzyme into the supernatant. A search of the amino acid sequence revealed no significant homology to any known aminopeptidases in the available data bases.

Amino Acid Sequence↗

PubMed2001

A controlled study of intravenous immunoglobulin combined with prednisone in the treatment of IBM.

OBJECTIVE: To investigate whether the combination of intravenous immunoglobulin (IVIg) with prednisone improves muscle strength and alters endomysial inflammation in patients with sporadic inclusion body myositis (s-IBM). BACKGROUND: In a previous controlled trial in s-IBM, IVIg did not significantly improve strength in spite of modest benefits in some muscle groups. The possibility that prednisone may have a synergistic effect with IVIg prompted another controlled trial. METHODS: Thirty-six patients with biopsy-proven IBM were randomized to receive IVIg or placebo monthly for 3 months. Before infusions, all patients were started on high-dose prednisone for 3 months. Primary outcome measures were differences in the 1) Quantitative Muscle Strength (QMT) testing; and 2) modified Medical Research Council (MRC) scores, between the patients randomized to IVIg + prednisone compared with those randomized to placebo + prednisone. Repeated open muscle biopsies were performed at random in 24 patients to determine changes in the number of autoinvasive T cells and necrotic muscle fibers. RESULTS: Nineteen patients were randomized to IVIg + prednisone and 17 to placebo + prednisone. No significant change was noted in muscle strength, assessed by QMT and MRC, from baseline to the 2nd, 3rd, or 4th month after treatment between the two groups. The number of necrotic fibers was reduced in the IVIg randomized group (p < 0.01), and the mean number of CD2+ cells was significantly decreased in both groups (p < 0.0001), denoting a steroid effect. CONCLUSION: IVIg combined with prednisone for a 3-month period was not effective in IBM. Endomysial inflammation was significantly reduced after treatment, but the reduction was not of clinical significance.

Aged↗

PubMed2001

Smad-mediated transcription is required for transforming growth factor-beta 1-induced p57(Kip2) proteolysis in osteoblastic cells.

Cyclin-dependent kinase inhibitory proteins (CKIs) are negative regulators of the cell cycle. Of all CKIs, only p57(Kip2) plays an essential role(s) that other CKIs cannot compensate for in embryonic development. Recently, we found that p57(Kip2) is degraded through the ubiquitin-proteasome pathway in osteoblastic cells stimulated to proliferation by transforming growth factor (TGF)-beta1 (Urano, T., Yashiroda, H., Muraoka, M., Tanaka, K., Hosoi, T., Inoue, S., Ouchi, Y., and Toyoshima, H. (1999) J. Biol. Chem. 274, 12197-12200). We report here that TGF-beta1-induced p57(Kip2) proteolysis is mediated through transcription by the Smad pathway. When the constitutively active form of the TGF-beta type I receptor ALK-5(TD) was ectopically expressed in osteoblastic cells, p57(Kip2) that had been accumulated by serum starvation causing the cell-cycle arrest was rapidly degraded in a manner analogous to TGF-beta1 stimulation. Moreover, Smad2 or Smad3 with Smad4 enhanced the proteolytic pathway of p57(Kip2). The degradation of p57(Kip2) evoked by TGF-beta1 was blocked by forced expression of an inhibitory Smad called Smad7 or by the addition of actinomycin D or alpha-amanitin. These results indicate that accelerated degradation of p57(Kip2) by TGF-beta1/Smad signaling is mediated through a newly synthesized factor(s) that modifies p57(Kip2) or the ubiquitin-proteasome pathway.

Animals↗

PubMed2001

Human T-cell leukemia virus type 1 tax protein activates transcription through AP-1 site by inducing DNA binding activity in T cells.

Human T-cell leukemia virus type 1 (HTLV-1) Tax protein induces the expression of various family members of the transcription factor AP-1, such as c-Jun, JunD, c-Fos, and Fra-1, at the level of RNA expression in T cells. We examined the activity of Tax in transcription through AP-1-binding sites (AP-1 site) in T cells. Transient transfection studies showed that Tax activated the expression of a luciferase gene regulated by two copies of an AP-1 site in the human Jurkat T-cell line. Tax activates the expression of viral and cellular genes through two different enhancers: a cAMP-responsive (CRE)-like element and a kappaB element. Two Tax mutants differentially activated expression of these two elements. Tax703 preferentially activated the kappaB element but not the CRE-like one, whereas TaxM22 showed the reverse. In addition, Tax703 and Tax, but not TaxM22, converted cell growth of a mouse T-cell line from being interleukin (IL)-2-dependent to being IL-2-independent. Unlike the wild-type Tax, Tax703 and TaxM22 only weakly activated the AP-1 site in the T-cell line. Thus, Tax seems to activate the AP-1 site via mechanisms distinct from those of kappaB or CRE-like elements, and the activation of the AP-1 site is dispensable for IL-2-independent growth of CTLL-2. Electrophoretic mobility shift assays showed that Tax induced strong binding activity to an AP-1 site in CTLL-2, whereas Tax703 did not, indicating that the induction of binding activity to the AP-1 site is essential for the transcriptional activation by Tax. The binding complex induced by Tax in CTLL-2 contained JunD and Fra-2. Other AP-1 proteins were undetectable. Activation of transcription through the AP-1 site in Jurkat cells by JunD and/or Fra-2 was weak. c-Jun, JunB, and c-Fos activation was greater, although the level was still less than that with Tax. Thus, the induction of AP-1 mRNA by Tax may not be sufficient for a complete activation of AP-1 site by Tax. Our results suggest that Tax activates the transcription of cellular genes with AP-1 sites by inducing the DNA-binding activity of AP-1 proteins in T cells, a mechanism distinct from those of CRE-like and kappaB elements.

Animals↗

PubMed2001

Expression of cell adhesion molecule and albumin genes in primary culture of rat hepatocytes.

Changes in the expression of cell adhesion molecule and albumin genes were investigated in primary cultures of rat hepatocytes with and without poly- N-p -vinylbenzyl-D-lactonamide (PVLA) coating of the dishes. In PVLA-coated cultures, hepatocytes aggregated into spheroids and expressed liver cadherin and albumin mRNAs at higher levels. In uncoated cultures, hepatocytes revealed low levels of cadherin and albumin mRNAs, but higher levels of integrin alpha-1 mRNA. The changes in mRNA levels of liver cadherin and integrin alpha-1 coordinated well with those in spheroid and monolayer formation of hepatocytes, respectively. These results suggest that, in the PVLA-coated culture, hepatocytes expressed cadherin at higher levels to promote cell-cell adhesion and further maintain the differentiated function, such as albumin secretion, for prolonged times.

Albumins↗

PubMed2001

Mammary ductoscopy for diagnosis and treatment of intraductal lesions of the breast.

BACKGROUND: Mammary ductoscopy (mammoscopy) is an ideal diagnostic method for intraductal lesions. The usefulness of mammoscopy for intraductal lesions was evaluated. METHODS: Mammoscopy was performed in 315 cases with nipple discharge. The mammoscopic findings of 46 breast cancer cases (47 lesions) and 109 intraductal papilloma cases (119 lesions) were compared with pathological findings. RESULTS: Carcinoma was recognized by mammoscopy in 38 of 47 lesions (80.9%). Intraductal masses were detected by mammoscopy in 115 of 119 intraductal papilloma lesions. The shape of the mass was classified as hemispheric, papillary, or flat protrusion. The hemispheric and papillary shapes were most common in cases of intraductal papilloma and the flat protrusion type was most common in cases of carcinoma. The amount of material collected by intraductal biopsy under mammoscopic observation was smaller in carcinoma than in intraductal papilloma because the carcinoma lesions were usually located in peripheral duct-lobular units and had weak tissue cohesion compared with that of intraductal papilloma. Of 133 intraductal biopsies performed for 69 intraductal papillomas, 17 biopsies yielded material insufficient for diagnosis in. The effectiveness of treatment by intraductal biopsy was recognized in 38 of 46 intraductal papillomas in which clinical follow-up continued for more than two years (82.6%). The therapeutic results of biopsy were poor in cases of multiple intraductal masses in multiple duct-lobular units. CONCLUSIONS: Mammoscopy contributes not only the diagnosis in cases of nipple discharge, but is also of benefit in the treatment of intraductal papilloma.

Breast Neoplasms↗

PubMed2001

Phalangeal microgeodic syndrome: MR appearance.

The authors describe the MR features of a case of microgeodic phalangeal syndrome in a 9-year-old boy. Roentgenograms showed multiple small areas of osteolysis in the middle phalanx of the right index finger. T1-weighted MR images showed lesions with diffuse low signal intensity not only in this phalanx but also in other phalanges. These lesions exhibited high signal intensity on T2-weighted images. Contrast-enhanced T1-weighted images showed a wide non-enhancing area in the middle phalanx of the index finger.

Child↗

PubMed2001

Contrast-enhanced three-dimensional helical CT for soft tissue tumors in the extremities.

OBJECTIVE: To evaluate the ability of contrast-enhanced three-dimensional (3D) helical computed tomography (CT) to image soft tissue tumors in the extremities. DESIGN AND PATIENTS: Forty-five consecutive patients with soft tissue tumors in the extremities were examined (mean age 46.2 years; 24 females, 21 males). Twenty-five patients had benign lesions and 20 had malignant lesions. All the patients underwent contrast-enhanced 3DCT scanning and magnetic resonance (MR) imaging preoperatively. All patients were surgically treated. Spiral CT scanning was performed with intravenous contrast enhancement. 3D reconstruction images were produced after thresholding, using Active-Windows (version 2.0, General Electric, Milwaukee, WI) software. 3DCT findings were compared in a masked fashion with the MR imaging and surgical findings regarding bone and major vessel invasion by the tumors. RESULTS: Forty-four of 45 tumors were satisfactorily imaged for the interpretation of their size, location and relationship to the skeleton and major vessels. One malignant tumor was judged on 3DCT to invade the major vessel, but the vessel proved to be normal at surgery. CONCLUSIONS: Contrast-enhanced 3D helical CT can be used for the evaluation of soft tissue tumors in the extremities, for preoperative surgical planning.

Adolescent↗

PubMed2001

Manifest Anxiety Scale for evaluation of effects of granisetron in chemotherapy with CDDP and 5FU for head and neck cancer.

The level of anxiety was examined before treatment by means of the Manifest Anxiety Scale (MAS) in 41 patients with squamous cell carcinoma of the head and neck. They received 5 days of neoadjuvant chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5FU). Granisetron (KYT) was administered daily from day 1 to day 5. Nausea, vomiting, appetite, and well-being were assessed during and after chemotherapy. The relation between the effects of KYT and anxiety was studied. Seventeen patients were proven to have anxiety and were compared with the other 24 patients. In patients with anxiety, the percentage well-being was significantly lower on days 1 and 2 (P=0.008, 0.001). The rate of freedom from nausea was significantly lower from day 4 to day 9 for anxiety patients (P=0.010-0.050). The percentage of anxiety patients without loss of appetite was significantly lower from day 6 to 9 (p=0.001-0.020). The rate of freedom from vomiting was significantly lower on days 4, 5 and 7 for anxiety patients (P=0.024, 0.024, 0.014). The results indicate that the effect of KYT was significantly lower from day 3 to day 7 for anxiety patients (P=0.008-0.045). The anxiety group had significantly poorer well-being at the beginning of chemotherapy, and were not responsive to KYT in the delayed phase. Our results prove that anxiety patients show delayed emesis, and the administration of KYT is considered insufficient. It may be important to co-administer a tranquilizer to any patient who exhibit anxiety as defined by the MAS, in order to reduce delayed emesis.

Adult↗