Decreasing cytokeratin 17 expression in head and neck cancer predicts nodal metastasis and poor prognosis: The first evidence.

OBJECTIVES: Cytokeratins (CKs) are mainly expressed in epithelial carcinomas and are valuable for making diagnoses and identifying metastatic status. Changes in the expression of individual CKs in certain carcinoma may be relevant to establishing a prognosis. However, the prognostic significance of CKs in head and neck squamous cell carcinoma (HNSCC) remains elusive. Herein, we investigated the diverse and unique expression patterns of Cytokeratin 13 (CK13) and Cytokeratin 17 (CK17) and assessed the role of CK17 as a predictor for HNSCC metastasis and prognosis. METHODS: CK13 and CK17 expressions were evaluated using immunohistochemical tissue microarray (TMA) analysis with 106 patients of HNSCC. To clarify the characterisation of CK17 expression with respect to its ability in predicting metastatic disease, an in vitro study of cells migration/invasion assays was conducted. Furthermore, the correlation of CK17 expression to clinicopathologic variables and prognosis was analyzed using a serial statistical method. RESULTS: CK13 was predominately expressed in non-cancerous tissues and was lost in HNSCC. Decreasing expression of CK17 correlated with cancerous cell migration and invasion (P < .0001) in an in vitro study. CK17 expression was lower in the N1 and N2 nodal metastases category compared to the N0 stage. Moreover, Kaplan-Meier survival analyses showed that a lower CK17 expression was associated with a poorer survival connotation in HNSCC patients (P < .05) with 10-year follow-up. CONCLUSION: Our findings provide the first evidence that CK17 under-expression might be a potential predictor of nodal metastasis and adverse prognosis.

Stimulatory effect of allantoin on imidazoline I1 receptors in animal and cell line.

Allantoin is known as the agonist of imidazoline receptor, especially the I2 subtype. Effect of allantoin on imidazoline I1 receptor (I1R) relating to reduction of blood pressure and its merit in steatosis are still obscure. Also, farnesoid X receptor (FXR) plays an important role in lipid homeostasis related to I1R activation. Thus, we administered allantoin into high fat diet (HFD)-fed mice showing hypertriglyceridemia and hypercholesterolemia. Allantoin significantly improved hyperlipidemia in HFD mice after 4 weeks of administration. Pretreatment with efaroxan, at a dose sufficient to inhibit I1R activation, attenuated the action of allantoin. In addition, in cultured HepG2 cells, allantoin increased the expression of farnesoid X receptor (FXR). The allantoin-induced FXR expression was blocked by efaroxan. Similar changes were observed in the expressions of FXR-targeted genes. Otherwise, allantoin also lowered systolic blood pressure (SBP) in HFD mice that can be blocked by efaroxan. Taken together, allantoin has an ability to activate I1R for improvement of metabolic disorders.

Ovarian carcinomatosis presenting as bilateral inguinal hernia: a brief report.

The differential diagnosis for what may seem an inguinal hernia may be complex, as lateral pain may be of many types of origin. We report the case of a 48-year-old female patient who presented with a history of painful, progressively protruding soft bulging masses over the bilateral inguinal area and a 20-year history of head cancer and hepatitis B virus. Pathological analysis, gynecological ultrasound and abdominal computed tomography scan were required to make final determination. Final diagnosis was Stage IV ovarian carcinomatosis, which responded to chemotherapy. Initial diagnosis of inguinal hernia should not rule out other potential diagnoses, particularly in complex cases with other risk factors.

Wound healing effects of porcine placental extracts on rats with thermal injury.

BACKGROUND: Placental extracts have been used as Chinese folk medicines to accelerate wound healing. However, the molecular mechanism of placental extracts on wound healing has not been identified. It is known that fibroblast growth factors (FGF) and transforming growth factors (TGF) are two key factors involved in wound healing. OBJECTIVES: To determine the molecular mechanism of placental extracts on wound healing. METHODS: The protein levels of both growth factors in rat skins with thermal injury were therefore studied to explore the molecular mechanism of placental extracts on wound healing. As cell proliferation is essential for wound healing, effects of placental extracts on fibroblast proliferation were also determined. RESULTS: As compared with the controls, the S phase of fibroblasts was significantly increased by 1.5-, 1.7- and 4.7-fold for 1, 10 and 30 mg mL(-1) of placental extracts, respectively. The increase of the S phase was not due to the minute amount of sex hormones in the placental extracts as the addition of equivalent amounts of hormones showed no increase of the S phase. In addition, a 2.5-fold increase of TGF-beta1 in wound skin biopsy was noticed with 30 mg mL(-1) of porcine placental extracts. The FGF levels in the wound skin receiving 30 mg mL(-1) of porcine placental extracts were also significantly increased compared with the controls. CONCLUSIONS: These ex vivo data support the observation that the application of 30 mg mL(-1) of placental extracts reduced the wound healing time by about 50%. To the best of our knowledge, this is the first report to explore the molecular mechanisms of porcine placental extracts on wound healing. These results may provide the insight into the potential use of porcine placental extracts as an alternative medicine for accelerating wound healing.

Choroidal infarction, anterior ischemic optic neuropathy, and central retinal artery occlusion from polyarteritis nodosa.

PURPOSE: Ocular ischemia from polyarteritis nodosa (PAN) is rare. The authors present a case of multifocal ocular infarction from PAN. METHODS AND RESULTS: A 70-year-old woman developed hand and foot numbness followed by intermittent blurred vision and binocular horizontal diplopia. Two weeks later, she suddenly lost vision in the right eye from a central retinal artery occlusion and then developed a left anterior ischemic optic neuropathy and bilateral triangular choroidal abnormalities consistent with infarction. Her erythrocyte sedimentation rate and C-reactive protein were elevated. Although giant cell arteritis was suspected, a multiple mononeuropathy was demonstrated by electromyogram and nerve conduction velocity studies. Biopsy specimens from her sural nerve and biceps muscle showed a necrotizing vasculitis with fibrinoid necrosis, consistent with PAN. CONCLUSIONS: Polyarteritis nodosa can produce ischemia of a variety of ocular structures, including the retina, choroid, and optic nerve. In our patient, all three structures were affected. To our knowledge, this is the first reported case of the triangular sign of Amalric in PAN.

Prognostic value of nm23 expression in stage IB1 cervical carcinoma.

BACKGROUND: The purpose of this retrospective study was to evaluate the patterns of nm23 expression in stage IB1 squamous cell carcinoma of the uterine cervix, to compare nm23 expression with clinicopathological findings and to assess its prognostic value. METHODS: Twenty-seven patients with stage IB1 squamous cell carcinoma of the uterine cervix underwent abdominal radical hysterectomy and pelvic lymph node dissection. Expression of nm23 was studied immunohistochemically, followed by amplification and direct sequencing of exons 4 and 5 of the nm23 gene. RESULTS: Overexpression of nm23 was detected in 18.5% of the tumors and low expression was seen in 33.3%, while negative expression was found in 48.1% of the tumors. Deep cervical stromal invasion (> or =1/2) was found to be associated with the increased risk of lymph node metastases (odds ratio = 17.5). A significantly lower percentage of patients survived when nm23 overexpression was observed (p = 0.0063). Univariate analysis revealed that tumor size (2-3.9 cm), lymph node metastasis, tumor invasion into parametria, tumor invasion into blood/lymph vessel, squamous cell carcinoma (> or =2 ng/ml) and nm23 overexpression had a significantly lower recurrence-free survival rate of the patients. None of the above factors was significant according to multivariate analysis. There were no mutations in exons 4 and 5 of the nm23 gene in stage IB1 squamous cell carcinoma of the uterine cervix. CONCLUSIONS: This study suggests that expression of nm23 may be indicative of an unfavorable prognosis in patients with stage IB1 squamous cell carcinoma of the uterine cervix.

Endoscopic comparison of the gastroduodenal safety and the effects on arachidonic acid products between meloxicam and piroxicam in the treatment of osteoarthritis.

Our objective was to evaluate the efficacy, the gastroduodenal safety, and the effects on arachidonic acid products of meloxicam, a new acidic enolic non-steroidal anti-inflammatory drug which preferentially inhibits cyclo-oxygenase-2 over cyclo-oxygenase-1, versus piroxicam in patients with osteoarthritis of the knee. Meloxicam 7.5 mg or piroxicam 20 mg daily was administered for 4 weeks in this double-blind parallel-groups randomised study. The efficacy for pain relief of the two tested medications was assessed by means of visual analogue scale and other clinical parameters. Pre- and post-treatment endoscopies were performed, and the findings were scored and recorded. The gastric fluid was aspirated at each time and prostaglandin E2, thromboxane B2 and leukotriene B4 were determined by ELISA. There was no significant difference between the groups regarding the primary efficacy. Changes in endoscopic findings by means of Lanza score showed statistically significant differences between the two treatment groups in favour of meloxicam at all sites--gastric, duodenal and total. Within-group comparisons showed a statistically significant difference (worsening) in gastric and total score with piroxicam, but no significant difference with meloxicam. The frequency of clinically relevant cases (total score >2) also showed a statistically significant worsening in the piroxicam group. The better GI tolerability of meloxicam was also suggested by fewer adverse GI events and no withdrawals due to adverse events compared with piroxicam. The pre-/post-study gastric juice concentration of PGE2, TXB2, and LTB4 in the meloxicam group was 135.2 +/- 85.8/71.2 +/- 32.2, 116.3 +/- 81.7/99.4 +/- 107.5 and 388 +/- 321/223 +/- 98 pg/ml respectively. The pre-/post-study gastric juice concentration of PGE2, TXB2 and LTB4 in the piroxicam group was 105.7 +/- 43.1/68.2 +/- 34.9, 94.0 +/- 50.9/105.9 +/- 121.1 and 625 +/- 1574/828 +/- 1464 pg/ml, respectively. Both meloxicam and piroxicam significantly inhibited gastric PGE2 levels after 4 weeks' treatment; however, there was no difference between these two groups. Neither of these medications had an effect on TXB2. Only meloxicam inhibited LTB4 concentration significantly, and the between-groups difference was significant. Meloxicam 7.5 mg once daily had better gastrointestinal tolerability and an efficacy comparable to that of piroxicam 20 mg over 4 weeks in patients with osteoarthritis of the knee.

The sympathetic nervous system promotes carbon tetrachloride-induced liver cirrhosis in rats by suppressing apoptosis and enhancing the growth kinetics of regenerating hepatocytes.

Norepinephrine is considered to possess potent anti-apoptotic action in regenerating hepatocytes. To clarify the role of the sympathetic nervous system in apoptosis that occurs in chronic liver damage and following the promotion of liver cirrhosis, we studied a carbon tetrachloride (CCl4)-induced liver injury model, using spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), and chemically sympathectomized WKY. At 24 h after CCl4 administration. acute damage, characterized by vacuolated hepatocytes in the centrilobular zone, was greater in SHR than in WKY. This vacuolated change in WKY hepatocytes was significantly reduced by chemical sympathectomy with 6-hydroxydopamine (6-OHDA). After 48 h, the acute damage was dramatically improved in each animal, without significant differences between the three groups. In chronic damage after weekly repetition of CCl4 treatment for 4 weeks, fibrosis was evident in SHR, while in the other groups there was only scant fibrosis in the centrilobular zone. After 8 weeks' repetition of CCl4, liver cirrhosis was seen only in SHR. The incidence of apoptotic cells in areas of both acute and chronic damage in WKY, detected by terminal deoxynucleotidyl transferase-dUTP nick end labeling, was significantly increased in comparison with that in SHR, and was further increased by 6-OHDA pretreatment. In contrast, there was significantly greater enhancement of the growth of hepatocytes in SHR than in WKY in both acute and chronic damage. Moreover. hepatocyte growth kinetics in WKY was significantly inhibited after sympathectomy in acute injury, as evidenced by immunohistochemistry for proliferating cell nuclear antigen (PCNA). In vitro, the amount of hepatocellular apoptosis induced by transforming growth factor-beta1 was significantly decreased by incubation with norepinephrine. These findings suggest that the anti-apoptotic effect of the sympathetic nervous system increases cell growth kinetics and promotes liver cirrhosis in this animal model.

Vaccination against gonadotropin-releasing hormone (GnRH) using toxin receptor-binding domain-conjugated GnRH repeats.

A method for the preparation of an immunogen containing multiple copies of a self-peptide in linear alignment was designed in order to overcome the difficulty of inducing an immune response to poorly immunogenic peptide antigens. DNA fragments encoding multiple repeats of the self-peptide were generated by a new technique, termed template-repeated polymerase chain reaction (TR-PCR), which could be subcloned into an expression vector for production of peptide repeats as an immunogen. This approach was tested by constructing fusion proteins containing the receptor-binding domain of Pseudomonas exotoxin A and multiple copies of the 10-residue sequence of the peptide hormone gonadotropin-releasing hormone (GnRH). Immunization of female rabbits with the immunogen that contained the exotoxin receptor-binding domain and 12 copies of GnRH (PEIa-GnRH12) resulted in the generation of high-titer antibodies specific for GnRH. Although at equal molar basis of the GnRH moiety, the immunogen that contained single copy of GnRH (PEIa-GnRH1) induced low-titer anti-GnRH antibodies. These observations suggest that the presence of multiple peptide repeats is a key factor in eliciting an immune response. In addition, anti-GnRH antibodies effectively neutralized GnRH activity in vivo, as demonstrated by the degeneration of the ovaries in the injected rabbits. Because anti-GnRH antibody could be functionally analogous to GnRH antagonist, which has been used to treat patients with ovarian cancer, vaccination of PEIa-GnRH12 presents a potential therapeutic application for the treatment of GnRH-sensitive ovarian cancer.

Prognostic value of p53 expression in stage IB1 cervical carcinoma.

The purpose of this retrospective study was to evaluate the patterns of p53 expression in stage IB1 squamous cell carcinoma of the uterine cervix, to compare p53 expression with clinicopathological findings, and to assess its prognostic value. 27 patients with stage IB1 squamous cell carcinoma of the uterine cervix underwent abdominal radical hysterectomy and pelvic lymph node dissection. Expression of p53 was studied immunohistochemically. Overexpression of p53 was detected in 33.3% of the tumors, low expression was seen in 11.1%, and negative expression was found in 55.6%. Deep cervical stromal invasion (> or = 1/2) was found to be associated with the increased risk of lymph node metastases (odds ratio = 17.5). A significantly lower percentage of patients survived when p53 overexpression was observed (p = 0.0315). Univariate analysis revealed that tumor size (2-3.9 cm), lymph node metastasis, tumor invasion into parametria, tumor invasion into blood/lymph vessels, squamous cell carcinoma antigen (> or = 2 ng/ml), and p53 overexpression had a significantly lower recurrence-free survival rate. None of these above factors obtained significance in the multivariate analysis. This study suggests that expression of p53 may be indicative of an unfavorable prognosis in patients with stage IB1 squamous cell carcinoma of the uterine cervix.

Development of DNA delivery system using Pseudomonas exotoxin A and a DNA binding region of human DNA topoisomerase I.

Gene therapy is defined as the delivery of a functional gene for expression in somatic tissues with the intent to cure a disease. Thus, highly efficient gene transfer is essential for gene therapy. Receptor-mediated gene delivery can offer high efficiency in gene transfer, but several technical difficulties need to be solved. In this study, we first examined the DNA binding regions of the human DNA topoisomerase I (Topo I), using agarose gel mobility shift assay, in order to identify sites of noncovalent binding of human DNA Topo I to plasmid DNA. We identified four DNA binding regions in human DNA Topo I. They resided in aa 51-200, 271-375, 422-596, and 651-696 of the human DNA Topo I. We then used one of the four regions as a DNA binding protein fragment in the construction of a DNA delivery vehicle. Based on the known functional property of each Pseudomonas exotoxin A (PE) domain and human DNA Topo I, we fused the receptor binding and membrane translocation domains of PE with a highly positively charged DNA binding region of the N-terminal 198 amino acid residues of human DNA Topo I. The resulting recombinant protein was examined for DNA binding in vitro and transfer efficiency in cultured cells. The results show that this DNA delivery protein is a general DNA delivery vehicle without DNA sequence, topology, and cell-type specificity. The DNA delivery protein could be used to target genes of interest into cells for genetic and biochemical studies. Therefore, this technique can potentially be applied to cancer gene therapy.

Bcl-2 accelerates retinoic acid-induced growth arrest and recovery in human gastric cancer cells.

The role of Bcl-2 as an anti-apoptotic protein has been well documented. In the present work, we present evidence that Bcl-2 may also be involved in cell growth regulation. SC-M1 is an unique cell line which responds to retinoic acid (RA) treatment with reversible growth arrest [Shyu, Jiang, Huang, Chang, Wu, Roffler and Yeh (1995) Eur. J. Cancer 31, 237-243]. In this study, when treated with RA, SC-M1/Bcl2 cells, which were generated by transfecting SC-M1 cells with bcl-2 DNA, were growth-arrested two days earlier than SC-M1/neo cells, which were generated by transfecting SC-M1 cells with vector DNA. This indicates that Bcl-2 accelerates RA-induced growth arrest. In addition to the accelerated growth arrest, RA-treated SC-M1/Bcl2 cells also recovered from growth arrest two days faster than SC-M1/neo cells after the removal of RA. Previously, we had identified the cyclin-dependent kinase inhibitor p21((WAF1/CIP1)) (p21) as a mediator of RA-induced growth arrest [Tsao, Li, Kuo, Liu and Chen (1996) Biochem. J. 317, 707-711]. In a search for the mechanism by which Bcl-2 affects growth regulation, we found that p21 gene expression was more prominent in SC-M1/Bcl2 cells than in SC-M1/neo cells in the presence of RA, but when RA was removed, p21 gene expression levels in SC-M1/Bcl2 cells were also reduced earlier than in SC-M1/neo cells. The present report is the first to show that Bcl-2 accelerates not only growth arrest but also recovery from growth arrest. Moreover, the close correlation between the effect of Bcl-2 on both RA-induced growth arrest and RA-induced p21 gene expression suggests the possibility that Bcl-2 affects cell growth through the mechanism of p21.

Tumor seeding of the jejunostomy site after transhiatal esophagectomy for esophageal carcinoma.

A 65-year-old male patient with squamous cell carcinoma of the esophagus had a transhiatal esophagectomy after a prophylactic tube jejunostomy. The tube was removed 3 weeks after surgery. Ten months later, a painless 2-cm abdominal mass was noted at the previous jejunostomy site. Subsequent segmental resection of the jejunum disclosed metastatic squamous cell carcinoma of the esophagus. It is possible that tumor seeding may develop at the jejunostomy site after transhiatal esophagectomy for esophageal carcinoma.

Stimulatory effect of octopamine on beta 3-adrenoceptors to lower the uptake of [14C]-deoxy-D-glucose into rat adipocytes in vitro.

1. The effect of octopamine on beta 3-adrenoceptors has been studied in isolated adipocytes of Wistar rats using uptake of [14C]-deoxy-D-glucose as the indicator. 2. Octopamine (0.1-1 nmol 1-1) induced a concentration-dependent decrease of [14C]-deoxy-D-glucose uptake into the adipocytes and this inhibition was not influenced by haloperidol at concentrations sufficient to block dopaminergic receptors. 3. Pindolol and propranolol reversed this inhibition of octopamine in a concentration-dependent manner. The effect of octopamine was reduced in the presence of Rp-cyclic AMPS triethylamine, the membrane-permeable antagonist of cyclic AMP (cAMP), indicating the mediation of cAMP in this inhibition. 4. A direct effect of octopamine on beta 3-adrenoceptors was proved using the application of antibodies. In the presence of an antibody for beta 3-adrenoceptors, the actions of octopamine were concentration-dependently reduced in a manner similar to the decrease of BRL37344-induced inhibitions. 5. The same degree of diminished activities for octopamine as that of BRL37344, the well-known specific agonist of beta 3-adrenoceptors, was also obtained in isoprenline-desensitized adipocytes. Insulin-stimulated uptake of [14C]-deoxy-D-glucose into adipocytes was not modified by isoprenaline induced desensitization. 6. These results suggest that octopamine can activate beta 3-adrenoceptors to lower the glucose uptake through an increase of cAMP in rat white adipocytes.

High frequency of cytotoxin-associated gene A in Helicobacter pylori isolated from asymptomatic subjects and peptic ulcer patients in Taiwan.

Cytotoxin-associated gene A (CagA), expressed in about 60% of H. pylori isolates in Western countries, may play a role in the pathogenesis of peptic ulcer. In this study, we determined the prevalence and significance of the H. pylori cagA gene and protein expression in Taiwan. Genomic DNA from antrum biopsies and H. pylori isolates were analyzed for cagA using polymerase chain reaction, Southern hybridization, or colony hybridization. CagA seropositivity was analyzed using Helico blots. In addition, Western blotting was performed to detect the CagA protein. About 94% of antrum tissues from both asymptomatic subjects and duodenal ulcer patients and all 76 H. pylori isolates (21 asymptomatic subjects, 39 with duodenal ulcers, 13 with gastric ulcers, 2 with gastric cancers, and 1 with mucosa-associated lymphoid tissue [MALT] lymphoma) were positive for the cagA gene. Moreover 77 out of 78 H. pylori-positive serum and all 27 H. pylori lysates had anti-CagA antibodies or CagA protein, respectively. H. pylori isolated from patients with various upper gastrointestinal diseases in Taiwan contained the cagA gene and expressed CagA protein at high frequencies.

Activation of beta3-adrenoceptors by exogenous dopamine to lower glucose uptake into rat adipocytes.

The effect of dopamine hydrochloride on beta3-adrenoceptors was studied in isolated adipocytes of Wistar rats using uptake of [14C]-deoxy-D-glucose (2-DG) as the indicator. Dopamine induced a concentration-dependent decrease of 2-DG uptake into adipocytes in a manner which was not modified by haloperidol at concentrations sufficient to block dopaminergic receptors. Failure of blockade was also observed in samples receiving the pretreatment with a mixture of SCH23390 and domperidone, the dopaminergic antagonists. Absence of dopaminergic receptors in rat white adipocytes was further supported by the findings that dopaminergic agonists did not modify the glucose uptake and the negative response to receptor antibodies in immunoblotting analysis. Pindolol and propranolol reversed this inhibition of dopamine in a concentration-dependent manner. However, this action of dopamine was not affected by prazosin at concentrations sufficient to block alpha-adrenoceptors. Effect of dopamine was reduced in the presence of Rp-cyclic AMPS triethylamine, the membrane-permeable antagonist of cyclic AMP (cAMP), indicating the mediation of cAMP in this inhibition. Direct effect of exogenous dopamine on beta3-adrenoceptors was identified using the antibody for beta3-adrenoceptors that reversed the inhibition of dopamine. These results suggest that dopamine can activate beta3-adrenoceptors to lower glucose uptake into rat white adipocytes which lack dopaminergic receptors.

Erosive esophagitis and Barrett's esophagus in Taiwan: a higher frequency than expected.

In contrast to Western countries, erosive esophagitis has been considered less common, Barrett's esophagus presumed less frequent, and hiatal hernia extremely uncommon in the Orient. However, accelerated modernization and adoption of Western customs have resulted in marked life-style changes in many Asians in the Orient that may potentially affect the frequency of erosive esophagitis and Barrett's esophagus in this population. Our aim was to determine the current frequency of erosive esophagitis, Barrett's esophagus, and other gastroesophageal reflux disease complications in self-referred Chinese patients undergoing upper gastrointestinal endoscopy in Taipei, Taiwan. Between July 1991 and June 1992, 464 consecutive patients underwent endoscopy for a variety of upper gastrointestinal symptoms at a major medical center. The presence of erosive esophagitis, strictures, Barrett's esophagus, and hiatal hernia was recorded. The extent of mucosal injury was determined by using the Savary-Miller grading system. Sixty-six (14.5%) patients were found to have erosive esophagitis, 9 (2%), Barrett's esophagus, and 32 (7%) hiatal hernias. Erosive esophagitis showed a male-to-female preponderance of 3.1:1. Disease severity increased with age and peaked during the sixth and seventh decades. We concluded that in contrast to previous experience, the Chinese population in Taiwan appears to have a higher frequency of erosive esophagitis, Barrett's esophagus, and hiatal hernia. Increased fat consumption, aging, and other possible factors are suggested as possible mechanisms.

The accuracy of the rapid urease test and 13C-urea breath test in the diagnosis of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (H. pylori) is an important predisposing factor in peptic ulcer disease. Many tests have been proposed, but there is no generally accepted single method for the detection of H. pylori. This study compared the four available methods in the detection of H. pylori. METHODS: One hundred and thirteen patients were studied with endoscopic biopsy. Biopsy specimens were examined with modified Giemsa stain and rapid urease (CLO) test. Serology (ELISA) and 13C-urea breath test (13C-UBT) were also performed. The 13C-UBT results were expressed at an excess delta 13CO2 excretion of 5 per mil as the upper limit. Multiple breath samples were collected 15, 30 and 60 minutes following 13C-urea ingestion (t = 15, 30, 60) in the first 60 patients. Gastric inflammatory changes were graded according to the Whitehead classification. The diagnostic gold standard was defined when three or more of the four test parameters showed positive. RESULTS: According to this diagnostic gold standard, the positive rates of H. pylori were 97.9% for duodenal ulcer, 81.8% for gastric ulcer, 47.6% for symptomatic gastritis and 13.6% for asymptomatics. Rapid urease test and the 13C-UBT had better sensitivity (93.6% and 96.2%) and accuracy (93.8% and 93.8%). The specificity and positive predictive value for rapid urease test was better than 13C-UBT (94.3% v.s. 88.6%, 97.3% v.s. 94.9% respectively). Modified Giemsa stain had the lowest sensitivity (87.2%), and the ELISA test had the lowest specificity (71.4%). Severity of the gastric inflammatory processes was directly correlated with the excess delta 13CO2 (r = 0.576). CONCLUSIONS: Both the CLO and 13C-UBT had higher accuracy in the detection of H. pylori. When the CLO test result is positive, there is little additional diagnostic benefit from performing other tests. If patients refuse endoscopic examination, 13C-UBT is a good alternative for the detection of H. pylori, either during diagnosis or follow-up after therapy.