Biomedical subjects

N Onoda

Publications and source records attributed to N Onoda.

At least 19 recordsLinked to original sources

PubMed2005

Efficacy of epidermal growth factor receptor-targeted molecular therapy in anaplastic thyroid cancer cell lines.

Anaplastic thyroid cancer is one of the most aggressive human malignancies and the outcomes of conventional therapy have been far from satisfactory. Recently, epidermal growth factor receptor (EGFR)-targeted therapy has been introduced as an alternative therapeutic strategy for highly malignant cancers. This study was undertaken to investigate the expression of EGFR in anaplastic thyroid cancer cell lines, and to explore the potential of therapies targeting EGFR as a new therapeutic approach. EGFR was universally expressed in anaplastic cancer cell lines at a variety of levels. Specific EGFR stimulation with epidermal growth factor showed significant phosphorylation of ERK1/2 and Akt, and resulted in marked growth stimulation in an anaplastic thyroid cancer cell line, which highly expressed EGFR. This EGFR-transmitted proliferation effect of the cancer cell line was completely inhibited by gefitinib, an EGFR tyrosine kinase inhibitor. Moreover, growth of xenografts inoculated in mice was inhibited in a dose-dependent manner with 25-50 mg kg(-1) of gefitinib administrated orally. Inhibition of EGFR-transmitted growth stimulation by gefitinib was clearly observed in anaplastic thyroid cancer cell lines. Our results suggested that EGFR-targeted therapy, such as gefitinib, might be worth further investigation for the treatment of anaplastic thyroid cancer.

Animals↗

PubMed2005

Odor-concentration coding in the guinea-pig piriform cortex.

By optical imaging of intrinsic signals, we demonstrated a possible code for odor concentration in the anterior piriform cortex of the guinea-pig. Odor-induced cortical activation, which primarily originated in layer II, appeared in a narrow band beneath the rhinal sulcus over the lateral olfactory tract, corresponding to the dorsal part of the anterior piriform cortex. Lower concentrations activated the rostral region of the band, whereas higher ones generated caudally spreading activation, and the site at which neural activation reached its maximum extent depended upon odor concentration. Different odors with low concentrations generated distinct but somewhat overlapping patterns in the rostral region of the band; the limited extent of cortical activity may be one focal domain for each odor. It was hard to judge, however, that odor-specific domains appeared in the anterior piriform cortex, because the strong stimuli induced largely overlapping patterns. Furthermore, the total area activated increased in proportion to concentrations raised to a power of 0.5-0.9. Importantly, these imaging results were confirmed with unit recordings which indicated a rostro-caudal gradient in odor-sensitivity among cortical neurons. Our results suggest that the dorsal part of the anterior piriform cortex may be associated with odor concentration. Therefore, in addition to recruitment of more olfactory sensory cells and glomeruli in response to stronger stimuli, a rostro-caudal gradient in axonal projections from mitral/tufted cells and/or in association fibers may play an important role in odor-concentration coding in the anterior piriform cortex.

Animals↗

PubMed2005

Developmental changes in oscillatory and slow responses of the rat accessory olfactory bulb.

Field potential, patch-clamp and optical recordings were performed in accessory olfactory bulb slices of postnatal rats following single electrical stimulation of the vomeronasal nerve layer. On the basis of differences in the components of the field potential, postnatal days were divided into three periods: immature (until postnatal day 11), transitional (postnatal days P12-17) and mature periods (after postnatal day 18). During the immature period, vomeronasal nerve layer stimulation provoked a characteristic damped oscillatory field potential, and the field potential recorded in the glomerular layer consisted of a compound action potential followed by several periodic negative peaks superimposed on slow components. Reduction in [Mg2+] enhanced slow components but did not affect oscillation, whereas an NMDA receptor antagonist, D-2-amino-5-phosphonovalerate, depressed slow components but did not affect the oscillation. During the mature period, slow components and the periodic waves (oscillation) disappeared. The time course of the field potential was similar to that in adults, suggesting that the accessory olfactory bulb reached electrophysiologically maturity at postnatal day 18. A non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, inhibited vomeronasal nerve layer-induced responses, while D-2-amino-5-phosphonovalerate had no effect, suggesting that NMDA and non-NMDA receptors are active in immature tissues, whereas non-NMDA receptors predominated in mature tissue. Results from whole-cell patch recordings in mitral and granule cells yielded results consistent with those from field potential and optical recordings. Further, a gradual decrease in number and frequency of oscillating waves was observed until postnatal day 17. Analyses of the depth profile of field potentials and current source density in immature tissue suggested that the oscillation and slow components originated in the glomerular layer but not in the external plexiform/mitral cell layer. Further, a new type of oscillation, which was independent of the reciprocal dendrodendritic synapses between mitral and granule cells, was detected. These data indicate that the lack of oscillatory suppression by immature NMDA receptors may play a critical role in the dynamic alteration of bulbar conditions.

Afferent Pathways↗

PubMed2005

Effects of N-methyl-D-aspartate glutamate receptor antagonists on oscillatory signal propagation in the guinea-pig accessory olfactory bulb slice: characterization by optical, field potential and patch clamp recordings.

To characterize the role of N-methyl-d-aspartate glutamate receptors in oscillations induced by a single electrical stimulation of the vomeronasal nerve layer, optical, field potential and patch clamp recordings were carried out in guinea-pig accessory olfactory bulb slice preparations. Bath application of the N-methyl-D-aspartate receptor antagonists, 2-amino-5-phosphonovaleric acid or MK-801, produced an increase in frequency of oscillating waves (oscillation) in external plexiform and mitral cell layers. The removal of Mg2+ from perfusate abolished oscillations, while subsequent application of 2-amino-5-phosphonovaleric acid or MK-801 restored oscillations. Vomeronasal nerve layer-evoked postsynaptic currents were analyzed by whole-cell clamp recordings from mitral and granule cells. A long-lasting excitatory postsynaptic current and periodic inhibitory postsynaptic currents, which were superimposed on the long excitatory postsynaptic current, were observed in mitral cells. The frequency of the periodic inhibitory postsynaptic currents correlated with the frequency of oscillations observed in the optical and field potential recordings. Furthermore, periodic inhibitory postsynaptic currents were blocked by puff application of bicuculline to the external plexiform layer/mitral cell layer, where mitral cells make dendrodendritic synapses with granule cells. In addition, puff application of the non-N-methyl-D-aspartate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, to the external plexiform layer/mitral cell layer suppressed an early phase of periodic inhibitory postsynaptic currents (membrane oscillation), whereas 2-amino-5-phosphonovaleric acid suppressed the late phase of periodic inhibitory postsynaptic currents. These data indicate that periodic excitatory postsynaptic currents of granule cells induce relevantly periodic inhibitory postsynaptic currents in mitral cells via dendrodendritic synapses and suggest that feedback inhibition regulates generation of oscillation via activation of non-N-methyl-d-aspartate glutamate receptors and gradual attenuation of oscillation via activation of N-methyl-D-aspartate receptors on granule cells.

Animals↗

PubMed2005

Efficacy of Helicobacter pylori eradication on the chronic mucosal inflammation of the remnant stomach after distal gastrectomy for early gastric cancer.

Although eradication of Helicobacter pylori (Hp) after early gastric carcinoma has been recommended, very limited studies have been reported and the method differs from standard therapy. Here, we attempted the eradication of Hp in the remnant stomach after surgery for primary gastric cancer with the standardized method. We examined efficacy and the safeness of the treatment. Thirty-three H. pylori-positive patients after distal gastrectomy were treated with proton pump inhibitor (PPI)-based triple therapies. After eradication, endoscopic and histological changes were classified on the basis of the Updated Sydney System. The eradication rate in the remnant stomach was 90.9% (30 out of 33 cases) after triple therapy. Temporal minor side effects were notified in 3 cases. After eradication, the remnant stomach showed significant decreases in inflammation- and activity-scores. Moreover, significant improvement in glandular atrophy to normal mucosa was found. In conclusion, PPI-based standard therapy is just as effective for Hp eradication in the remnant stomach than it is in the non-operative stomach. Eradication therapy could be performed safely and resulted in a significant improvement in inflammation and atrophy of the mucosal layer in the remnant stomach after early gastric cancer surgery.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2004

Convergence of olfactory and gustatory connections onto the endopiriform nucleus in the rat.

Electrical and optical recordings were made from slice preparations including the piriform and gustatory cortices. Electrical stimulation of the gustatory cortex evoked a characteristic field potential in the endopiriform nucleus. A field potential was induced in the endopiriform nucleus by stimulation of the piriform cortex. Voltage-sensitive dye studies showed that stimulation of the piriform cortex induced signal propagation from the piriform cortex to endopiriform nucleus, whereas stimulation of the gustatory cortex did the same from the gustatory cortex to endopiriform nucleus via the agranular division of the insular cortex. After stimulation of the endopiriform nucleus, optical signals propagated not only to the piriform cortex but also to the gustatory cortex via the agranular division of the insular cortex. The olfactory and gustatory pathways appeared to be reciprocally connected. Unit recordings indicated that olfactory and gustatory activity converged onto a single neuron of the endopiriform nucleus. It is suggested that the cortical integration of olfactory and gustatory information could modulate mechanisms involved in food selection and emotional reactions relating to the chemical senses.

Animals↗

PubMed2004

A case of secondary hyperparathyroidism whose high turnover bone improved after the direct injection of acetic acid into the parathyroid glands.

A 48-year-old male was admitted to our hospital because of increasing knee pain and thigh muscle weakness. He had been undergoing hemodialysis for 15 years. His serum intact PTH value was 1,600 pg/ml with elevated ALP (387 IU/l) and osteocalcin (400 ng/ml). Ultrasound (US) examination disclosed 2 enlarged parathyroid glands. Because of poor cardiac function, an US-guided acetic acid injection into the enlarged parathyroids (percutaneous acetic acid injection therapy; PAIT) was performed. Soon after the PAIT, his arthralgia disappeared. Serum PTH fell to 220 pg/ml with the regression of bone marker 1 year following the PAIT. The size of his parathyroid glands dramatically regressed and 1 of the enlarged glands finally disappeared. Repeated bone biopsies following double tetracycline labeling showed a significant improvement from osteitis fibrosa to the mild lesion. This is the first known case report of severe secondary hyperparathyroidism whose PTH and high turnover bone was successfully managed by the direct injection of acetic acid into the parathyroid glands. As long as we pay attention to avoiding recurrent nerve palsy induced by acetic acid, US-guided PAIT may be an alternative to percutaneous ethanol injection therapy (PEIT) or surgical parathyroidectomy (PTx).

Acetic Acid↗

PubMed2003

Percutaneous calcitriol injection therapy (PCIT) for secondary hyperparathyroidism: multicentre trial.

A multicentre trial of percutaneous calcitriol injection therapy (PCIT) was designed to evaluate its clinical usefulness. During a 12-week period, measurement of intact PTH concentration, and other parameters, and ultrasonography were carried out in conjunction with PCIT in 19 haemodialysis patients with secondary hyperparathyroidism and enlarged parathyroid glands (PTGs) that were resistant to vitamin D pulse therapy. Calcijex was injected directly into the PTG three times per week on the patient's non-dialysis days: eight patients received a 2 microg/ml preparation (group A) and 12 received 1 microg/ml (group B). A strong clinical effect was observed in group A compared with group B, which suggests that the effect of calcitriol by direct injection is stronger when there is a higher concentration of calcitriol in the PTG. In group B, the cases with an initial intact PTH concentration <1000 pg/ml and a single enlarged PTG had a good response to the treatment. Concentrations of calcium and phosphate were not significantly changed in either group. All cases had decreased blood flow in the PTG after three episodes of PCIT and, although the size of the PTG was unchanged, or even a little increased, immediately after the treatment, it decreased gradually over 2-6 weeks. PCIT may be effective for comparatively slight secondary hyperparathyroidism, but further investigation is necessary because there were comparatively few cases.

Aged↗

PubMed2002

Thoracoscopic internal mammary sentinel node biopsy for breast cancer.

Sentinel node (SN) biopsy has changed the management of breast cancer. This pilot study assessed the utility of lymphatic mapping and thoracoscopic SN biopsy for internal mammary node (IMN) staging. Forty-nine breast cancer patients underwent lymphatic mapping using 99mTc-tin colloid. Patients with IMSNs underwent thoracoscopic biopsy. Lymphoscintigraphy showed IMSNs in 15 of 49 cases (31%). The incidence of IMN drainage was relationed to age and tumor location; 50% of patients younger than age 40 and 43% with tumors located in inner quadrants had IMN drainage. The thoracoscopic procedure was performed in 11 of 15 patients, and 18 IMSNs were removed; the time of the procedure ranged from 20 to 60 min. No patients had complications from the procedure. Two of 11 patients (18%) had IMSN metastasis, and one of them had only IMN metastasis. Lymphatic mapping and the thoracoscopic approach were useful for IMSN biopsy. They may enable the physician to make an appropriate treatment decision for breast cancer.

Adult↗

PubMed2002

Dimensions of temperament as vulnerability factors in depression.

In order to evaluate the hypothesis that one set of genetic risk factors may be common to disorders and dimensions of temperament, whereas environmental risk factors are disorder specific, we have conducted a genetic analysis of dimensions of temperament and symptoms of depression in about 201 pairs of monozygotic and dizygotic twins. Dimensions of temperament associated with novelty seeking, harm avoidance, reward dependence, and persistence were measured by using the Temperament and Character Instruments developed by Cloninger, and depressive symptoms were measured using the Hospital Anxiety and Depression Scale. Differences among individuals on these measures can be explained by differences in their genes and in their environmental experiences. There are no differences between the sexes in gene action affecting temperament. Each dimension of temperament is genetically dependent, and genetic variations in symptoms of depression are largely dependent on the same factors that affect the temperament. Temperament is closely associated with vulnerability to depressive symptoms.

Adolescent↗

PubMed2002

Abnormal expression and function of Fas ligand of lacrimal glands and peripheral blood in Sjögren's syndrome patients with enlarged exocrine glands.

The objective of our study was to investigate the possibility of Fas ligand protein abnormalities in certain types of Sjögren's syndrome patients with enlarged exocrine glands. Fas ligand expression by lymphocytes infiltrating the lacrimal glands and by peripheral blood monocytes in Sjögren's syndrome patients with enlarged exocrine glands was assessed immunohistologically and by immunoblotting. Cytotoxicity of peripheral blood monocytes and sensitivity to steroids in Sjögren's syndrome patients with enlarged exocrine glands were studied by functional assay. Minimal Fas ligand expression was detected in the lymphocytes of the lacrimal glands and a decreased level of Fas ligand was found in peripheral blood monocytes as assessed by immunoblotting. Functional assay confirmed the decreased cytotoxicity of lymphocytes in Sjögren's syndrome patients with enlarged exocrine glands, and that it is not affected by anti-Fas ligand antibody. By contrast, the sensitivity of lymphocytes in Sjögren's syndrome patients with enlarged exocrine glands to steroids was increased. These observations suggest that abnormal expression and function of Fas ligand occurs in Sjögren's syndrome patients with enlarged exocrine glands.

Adrenal Cortex Hormones↗

PubMed2002

Immunohistochemical detection of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, in human chronic cholecystitis.

AIMS: Recent studies suggest that oxidative DNA damage induced during chronic inflammation may play a role in carcinogenesis in some organs. Although gallbladder carcinomas are frequently observed with a background of chronic cholecystitis, little is known about oxidative DNA damage in chronic cholecystitis. The aims of this study were to investigate the expression of 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, in normal and chronically inflamed human gallbladder mucosa and compare its expression with clinicopathological findings. METHODS AND RESULTS: 8-OHdG expression was immunohistochemically examined using a monoclonal antibody against 8-OHdG in human gallbladder specimens. In normal gallbladder (n=5), no 8-OHdG expression was observed. In contrast, nuclear expression of 8-OHdG was detected in 28 of 31cases (90.3%) in gallbladder epithelial cells with chronic cholecystitis. The positive cells were predominantly observed in the areas of active inflammation with prominent cell infiltration. Quantitative analysis revealed that the number of 8-OHdG+ cells (labelling index) significantly (rs=0.671, P < 0.05) correlated with the degree of the activity of mucosal inflammation, while gender, age, and the presence of gallstones did not influence the index. CONCLUSIONS: Oxidative DNA damage is common in chronic cholecystitis, suggesting a possible link between chronic inflammation and gallbladder carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2001

SF20/IL-25, a novel bone marrow stroma-derived growth factor that binds to mouse thymic shared antigen-1 and supports lymphoid cell proliferation.

Using a forward genetic approach and phenotype-based complementation screening to search for factors that stimulate cell proliferation, we have isolated a novel secreted bone marrow stroma-derived growth factor, which we termed SF20/IL-25. This protein signals cells to proliferate via its receptor, which we have identified as mouse thymic shared Ag-1 (TSA-1). Enforced expression of TSA-1 in IL-3-dependent Ba/F3 cells that do not express endogenous TSA-1 rendered cells to proliferate in a dose-dependent manner when stimulated with SF20/IL-25. FDCP2, a factor-dependent hemopoietic cell line that expresses endogenous TSA-1, could also be stimulated to proliferate with SF20/IL-25. Binding of SF20 to TSA-1 was blocked by anti-TSA-1 Ab and SF20-induced proliferation of TSA-1-expressing cells was inhibited by anti-TSA-1. In vitro assay revealed that SF20/IL-25 has no detectable myelopoietic activity but supports proliferation of cells in the lymphoid lineage.

Amino Acid Sequence↗

PubMed2001

Synchronized population oscillation of excitatory synaptic potentials dependent of calcium-induced calcium release in rat neocortex layer II/III neurons.

We examined the roles played by calcium-induced calcium release from ryanodine-sensitive calcium stores in induction of neocortical membrane potential oscillation by using caffeine, an agonist of ryanodine receptors. Intracellular recordings were made from neurons in layer II/III of rat visual cortex slices in a caffeine-containing medium. White matter stimulation initially evoked monophasic synaptic potentials. As low-frequency stimulation continued for over 10 min, an oscillating synaptic potential gradually became evoked, in which a paroxysmal depolarization shift was followed by a 8-10-Hz train of several depolarizing wavelets. This oscillating potential was not induced in a medium containing no caffeine with 2 or 0.5 mM [Mg2+](o). Under blockade of N-methyl-D-aspartate receptors, induction of this oscillating potential failed even with caffeine application. Experiments with the calcium store depletor, thapsigargin, revealed that this oscillating potential is induced in a manner dependent on intracellular calcium release. Dual intracellular recordings revealed that the oscillation was synchronized in pairs of layer II/III neurons. The oscillating potential was detectable by field potential recordings also, suggesting that the present oscillation seems to reflect a network property.

Animals↗

PubMed2001

A novel secreted form of immune suppressor factor with high homology to vacuolar ATPases identified by a forward genetic approach of functional screening based on cell proliferation.

In the search for stromal-derived growth factors, we have identified a novel secreted short form of immune suppressor factor (ISF) using a combination of a genetic approach and retrovirus-mediated functional screening. This protein, which we termed ShIF, was isolated based on its ability to support proliferation of a mutant clone S21, which was established from Ba/F3 cells that are usually interleukin-3-dependent but became dependent on a stroma cell line ST2 after chemical mutagenesis. ISF, a membrane protein harboring six transmembrane domains, was reported to have immunosuppressive functions. The coding region of ShIF started from the third transmembrane domain of ISF. Biochemical analysis demonstrated that ShIF was expressed in both the secreted and membrane-bound forms of 27-kDa protein, which was supposed to have an internal ATG present in the third transmembrane domain of ISF as a start codon. In addition to the full-length form of ISF, a major protein with a molecular size of 27 kDa was also expressed through the proteolytic process of ISF. ShIF resembles this naturally occurring short form of ISF (sISF). Deletion analysis of the major domains of ISF cDNA revealed that ShIF is an active functional domain of ISF with a capability to support proliferation of S21 cells. Enforced expression of ShIF in MS10 cells, bone marrow stroma cells that do not express endogenous ShIF or ISF, conferred on the cells an ability to support the growth of S21 cells as well as bone marrow cells. Interestingly, ShIF shows a high sequence homology to the C-terminal part of a 95-kDa yeast vacuolar H (+)-ATPase subunit, Vph1p (39%), and a 116-kDa proton pump (VPP1) (54%) of the rat and bovine synaptic vesicle. Therefore, it is possible that ShIF also acts as a proton pump and somehow prevents the cells from undergoing apoptosis.

Amino Acid Sequence↗

PubMed2001

Nicotine affects the signaling of the death pathway, reducing the response of head and neck cancer cell lines to DNA damaging agents.

BACKGROUND: Growing evidence suggests that tobacco can affect the responsiveness of cancer cells to treatment, particularly those of head and neck cancer. This article describes the effects of nicotine on the signaling of the death pathway, resulting in a decreased cytotoxicity of various anticancer agents such as cisplatin and gamma-radiation. METHODS: Colony-forming assays (CFA), using the head and neck cancer cell lines UMSCC10b and UMSCC5 and DNA fragmentation assays, were used to determine the effect of nicotine on cytotoxicity of various anticancer agents, whereas PCR and a JNK activity test were used to study the effect of nicotine on message expression levels and activity of the JNK signaling pathway. RESULTS: Nicotine consistently reduced the cytotoxic effect of DNA-damaging agents, such as cisplatin, UV, and gamma radiation, in UMSCC10b cells, increasing their IC(50) values by twofold, 1.7-fold, and 1.8-fold, respectively. These results were confirmed in a second squamous cell carcinoma cell line (UMSCC5), demonstrating an increase in IC(50) values for cDDP by twofold and 1.9-fold in the UMSCC10b andUMSCC5, respectively. In addition, nicotine reduced the DNA fragmentation 48 h after cDDP exposure in UMSCC10b and UMSCC5 cell lines by 30% and 33%, respectively. The latter, however, was not the result of an effect of nicotine on either the uptake of cDDP or repair of the cDDP-DNA-adducts. To further substantiate the adverse effect of nicotine, the JNK and gadd153 signaling pathways were studied. JNK activity was decreased by 1.8-fold, as well as the expression of its downstream target c-jun (1.9-fold), when tumor cells were exposed to cisplatin in the presence of nicotine. In addition, the gadd153 message was affected and reduced by 1.8-fold. CONCLUSIONS: Nicotine adversely affects the cytotoxicity of DNA-damaging agents. Nicotine does not interfere with the repair of the damage but directly affects the signaling of the death pathway, reducing the signaling of the JNK1 pathway. The latter results in a decrease in efficacy of the anticancer treatment in tumors exposed to nicotine.

Antineoplastic Agents↗

PubMed2001

Prevalence of Helicobacter pylori infection in gastric remnant after distal gastrectomy for primary gastric cancer.

BACKGROUND: The development of a second primary cancer in the gastric remnant after gastrectomy for early gastric carcinoma is a problem, and eradication of Helicobacter pylori after the operation has been recommended. However, to date, practical indications for H. pylori eradication after gastric cancer surgery have not yet been reported. METHODS: We examined H. pylori infection in the gastric remnant after distal gastrectomy for primary gastric cancer. One hundred and nine patients who had had a gastrectomy were studied. Endoscopic findings and results from the urease test, bacteriologic assessment, serological test, and histopathological examination were analyzed. RESULTS: Seventy-one patients (65.1%) were judged to be positive for H. pylori infection. The prevalence of H. pylori infection was found to be significantly decreased in older patients, patients in whom the operation had been performed a long time before examination, patients with symptoms, and patients with severe reflux gastritis. On the other hand, histologically, chronic and acute gastritis correlated significantly with H. pylori infection. H. pylori prevalence was highest in mildly atrophic mucosa and decreased with more extensive atrophic changes of the mucosa. CONCLUSIONS: The persistence of H. pylori-related active gastritis in the gastric remnant after gastric cancer surgery was suggested in younger patients with mild atrophic gastritis and without reflux gastritis. These patients may be the best candidates for H. pylori eradication therapy.

Adult↗

PubMed2001

The value of ultrasound-guided fine-needle aspiration cytology for thyroid nodules: an assessment of its diagnostic potential and pitfalls.

This study was conducted to assess the diagnostic potential and pitfalls of performing fine-needle aspiration cytology (FNAC) for thyroid nodules. We retrospectively analyzed 1,012 aspirated samples obtained from 806 thyroid nodules by the ultrasound (US)-guided method. Of these 806 nodules, 226 (31%) had been surgically treated, 152 (67%) of which were histologically diagnosed as malignant. The rate of sufficient aspirate was 82%, being lower in nodules with a diameter of less than 5mm (73%, P = 0.10); either calcified (77%, P = 0.043) or benign (72%, P = 0.0002). The accuracy of FNAC was 75%, the rate of indeterminate diagnosis was 16%, the false negative rate was 13%, and the positive malignancy rate was 99%. The rate of indeterminate diagnosis was higher in adenomatous goiter, follicular carcinoma, and malignant lymphoma, at P = 0.015, P = 0.0008, and P = 0.035, respectively. The accuracy was lower in follicular carcinoma and malignant lymphoma (both at P = 0.013). Sufficient aspirate was finally obtained from 701 (87%) of the 806 nodules by repeated aspiration. Of 152 malignant nodules, 28 (18%) were diagnosed after two or more aspirations, and the accuracy was improved to 81% by repeating the procedure. These findings indicated that repeated aspiration may be a simple and effective method of improving the diagnostic potential of FNAC.

Adenocarcinoma, Follicular↗