Biomedical subjects

Chih-Hung Chen

Publications and source records attributed to Chih-Hung Chen.

At least 19 recordsLinked to original sources

PubMed2007

Osmotherapy with hypertonic saline attenuates water content in brain and extracerebral organs.

OBJECTIVE: Because of their beneficial effects in patients with hemorrhagic shock and multiple-system trauma, hypertonic saline solutions are increasingly being used perioperatively for volume resuscitation. Although the anti-edema effects of hypertonic saline on brain are well documented in a variety of brain injury paradigms, its effects on the water content on other organs has not been studied rigorously. In this study, we tested the hypothesis that a) hypertonic saline when given as an intravenous bolus and continuous infusion attenuates water content of small bowel, lung, and brain in rats without neuro-injury; and b) attenuation of stroke-associated increases in lung water is dependent on achieving a target serum osmolality. DESIGN: Prospective laboratory animal study. SETTING: Research laboratory in a teaching hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: In the first series of experiments, under controlled conditions of normoxia, normocarbia, and normothermia, spontaneously breathing, halothane-anesthetized (1.0-1.5%) adult male Wistar rats (280-320 g) were treated in a blinded randomized fashion with 7.5% hypertonic saline or 0.9% normal saline in a 8-mL/kg intravenous infusion for 3 hrs followed by a continuous intravenous infusion (1 mL/kg/hr) of 5% hypertonic saline or normal saline, respectively (n=10 each), for 48 hrs. A second group of rats were treated with continuous infusion only for 48 hrs of either 7.5% hypertonic saline or normal saline (1 mL/kg/hr) (n=10 each) without an intravenous bolus. Naïve rats served as controls (n=10). Tissue water content of small bowel, lung, and brain was determined by comparing the wet-to-dry ratios at the end of the experiment. In a second series of experiments, rats (n=94) were subjected to 2 hrs of transient middle cerebral artery occlusion by the intraluminal occlusion technique. At 6 hrs following middle cerebral artery occlusion, rats were treated in a blinded randomized fashion with a continuous intravenous infusion of normal saline, 3% hypertonic saline, or 7.5% hypertonic saline for 24, 48, 72, and 96 hrs. Surgical shams served as controls (n=7). Hypertonic saline was instituted as chloride/acetate mixture (50:50) in all experiments. Serum osmolality was determined at the end of the experiment in all animals. MEASUREMENTS AND MAIN RESULTS: In rats without neuro-injury that received intravenous bolus followed by a continuous infusion, lung water content was significantly reduced with hypertonic saline (73.9+/-1.1%; 359+/-10 mOsm/L) (mean+/-sd) compared with normal saline treatment (76.1+/-0.53%; 298+/-4 mOsm/L) as was water content of small bowel (hypertonic saline, 69.1+/-5.8%; normal saline, 74.7+/-0.71%) and brain (hypertonic saline, 78.1+/-0.87%; normal saline, 79.2+/-0.38%) at 48 hrs. Stroke-associated increases in lung water content were attenuated with 7.5% hypertonic saline at all time points. There was a strong correlation between serum osmolality and attenuation of stroke-associated increases in lung water content (r=-.647) CONCLUSIONS: Bowel, lung, and brain water content is attenuated with hypertonic saline when serum osmolality is >350 mOsm/L without adverse effect on mortality in animals with and without neuro-injury. Attenuation of water content of extracerebral organs with hypertonic saline treatment may have therapeutic implications in perioperative fluid management in patients with and without brain injury.

Animals↗

PubMed2006

Another option to treat Kümmell's disease with cord compression.

The efficiency of short-segment fixation with transpedicle body augmenter (a titanium spacer with bone-ingrowth porous surface, TpBA) to treat Kümmell's disease with cord compression (stage III) was retrospectively evaluated. No laminectomy or instrumentation reduction was done. Inclusion criteria included Frankel CDE, single-level within T10-L2. FU rate was 88%, i.e. 21 cases were included. Frankel function classification was 6E9D6C. Mean age was 72+/-8 years. F:M was 16:5. FU period was 48 M (range, 30-76 M). The hospitalization was 4.5+/-2.2 days; operation time, 70.4+/-17.2 min; blood loss, 150+/-72 cc. Final Frankel class was 20E1D. Complications included two superficial infection and one pneumonia. Body height and kyphosis were all corrected significantly and well preserved at the final visit. No TpBA dislodgement or implant failure was noted; however, three cases developed new compression fractures. The clinical outcome showed 81% with P1 or P2 by Denis pain scale. This method can decompress spinal canal, maintain kyphosis correction and vertebral restoration, prevent implant failure, and attain good clinical results.

Aged↗

PubMed2006

Weekly short infusion of taxotere at a 4 week cycle in Chinese patients with advanced NSCLC who have failed or relapsed after the frontline platinum-based non-taxane chemotherapy--a Phase II trial.

BACKGROUND: This Phase II study was conducted to evaluate the efficacy and toxicity of weekly docetaxel at a 4 week cycle in second-line therapy for patients with advanced non-small cell lung cancer (NSCLC) who failed to respond or relapsed after the frontline platinum-based, non-taxane regimen. METHODS: Patients with histologically confirmed and progressive NSCLC after one platinum-based, non-taxane regimen were eligible for this study. Performance status of 0-2 and adequate organ function were required. Patients were treated with docetaxel 40 mg/m(2)/week for three consecutive weeks then following 1 week of rest. Cycles were repeated every 4 weeks for a maximum total of six cycles. Docetaxel was administered intravenously for 30 min with dexamethasone premedication. RESULTS: Fifty-three patients were eligible for this study. Hematologic toxicity was very mild and with the major toxicity of anemia. Non-hematologic toxicities were modest, Grades 3-4 mucositis, diarrhea and peripheral neuropathy occurred in 6-13% of patients and caused dose modifications. Fatigue (48%) was common but not severe with only 6% of Grades 3-4 toxicity. The overall response rate (ORR) was 13% [95% confidence interval (CI), 3.9-23%]. The median survival time (MST) for all patients was 25.0 weeks (95% CI, 12.7-37.3), and the 1 year survival was 31% (95% CI, 17-58%). For patients with PS 0-1, MST was 29.7 weeks and 1 year survival was 36%. CONCLUSIONS: Weekly docetaxel appeared to be well tolerated as second-line therapy for patients with NSCLC. The efficacy for this regimen was comparable with the standard 3 week schedule but hematologic toxicity was markedly reduced. A schedule of three consecutive weeks, with a 1 week break, may diminish the frequency of fatigue and diarrhea when compared with a schedule of six consecutive weeks.

Adult↗

PubMed2006

Evaluation of the associations between the single nucleotide polymorphisms of the promoter region of the tumor necrosis factor-alpha gene and nasopharyngeal carcinoma.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine and may act as an endogenous tumor promoter. Single nucleotide polymorphisms (SNPs) of the TNF-alpha gene promoter region have been found to be associated with certain cancers. We conducted a case-control study to evaluate the association between these SNPs and nasopharyngeal carcinoma (NPC). METHODS: We used polymerase chain reaction followed by restriction fragment length polymorphism analysis to determine the -308 TNF-alpha promoter genotypes of 89 NPC patients and 360 healthy controls. In 23 NPC patients and 50 controls, we determined the sequence from -1065 to -101 nucleotides of the TNF-alpha gene promoter region to detect SNPs. RESULTS: In comparison with the controls, the NPC patients had higher proportions of men and carriage of IgA antibodies against the capsid antigen of Epstein-Barr virus, but had a similar carrier rate of the -308A allele (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.7-2.0). The carriage of the -308A allele was not associated with the occurrence of NPC in comparison with -308G homozygosity. We also found no significant differences in the distributions of allelic variants of the -1031, -863, -857, and -806 loci of the TNF-alpha promoter region, but observed a lower carrier rate of the novel -806T allele in the NPC patients (OR, 0.3; 95% Cl, 0.0-2.9). CONCLUSION: Allelic variants of the TNF-alpha promoter gene may not be used as biomarkers of susceptibility to NPC. The role of the -806T allele needs to be studied further.

Adult↗

PubMed2006

Comparison of the anesthesia profiles between sevoflurane-nitrous oxide and propofol-nitrous oxide conveyed by laryngeal mask airway in patients undergoing ambulatory gynecological surgery.

BACKGROUND: The major purpose of this study is to evaluate and compare the clinical characteristics of sevoflurane-nitrous oxide and propofol-nitrous oxide anesthesias conveyed by laryngeal mask airway (LMA) in patients for gynecological procedures. METHODS: Eighty female patients were randomly assigned to one of the two groups: Group I, inhalational induction at vital capacity with 8% sevoflurane and 67% nitrous oxide in oxygen; Group II, induction with intravenous propofol at 2 mg/kg followed by intravenous infusion at 6 mg/kg/hr. The LMA was inserted after loss of response to jaw thrusting. After successful insertion, in group I anesthesia was maintained with sevoflurane and 67% nitrous oxide in O2 and in group II anesthesia was maintained with propofol at 6 mg/kg/hr and nitrous oxide 67% in oxygen. Anesthetic profiles, including insertion event, postoperative nausea and vomiting, and hemodynamic alterations were compared. RESULTS: Demographic data were comparable in the two groups. After induction, in group II unconsciousness was produced 59 sec shorter than that in group I for placement of LMA. Group I had a higher statistically significant rate of cough upon induction, and by the same token postoperative nausea and vomiting. There were no significant differences in hemodynamic alterations, as well as time to open eyes on command, and time to regain orientation. CONCLUSIONS: Intravenous propofol in combination with 67% nitrous oxide in oxygen technique provided better clinical profiles, compared with sevoflurane-nitrous oxide technique through the use of LMA in gynecological patients undergoing ambulatory short procedures.

Adult↗

PubMed2005

Plasma arginine-vasopressin following experimental stroke: effect of osmotherapy.

Neurohumoral responses have been implicated in the pathogenesis of ischemia-evoked cerebral edema. In a well-characterized animal model of ischemic stroke, the present study was undertaken to 1) study the profile of plasma arginine-vasopressin (AVP), and 2) determine whether osmotherapy with mannitol and various concentrations of hypertonic saline (HS) solutions influence plasma AVP levels. Halothane-anesthetized adult male Wistar rats were subjected to 2 h of middle cerebral artery occlusion with the intraluminal filament technique. Plasma AVP levels (means +/- SD) were significantly elevated at 24 h (42 +/- 21 pg/ml), 48 h (50 +/- 28 pg/ml), and 72 h (110 +/- 47 pg/ml), and returned to baseline at 96 h (22 +/- 15 pg/ml) following middle cerebral artery occlusion compared with sham-operated controls (14 +/- 7 pg/ml). Plasma AVP levels at 72 h were significantly attenuated with 7.5% HS (37 +/- 8 pg/ml; 360 +/- 11 osmol/l) compared with 0.9% saline (73 +/- 6; 292 +/- 6 osmol/l), 3% HS (66 +/- 8 pg/ml; 303 +/- 12 osmol/l), or mannitol (74 +/- 9 pg/ml; 313 +/- 14 osmol/l) treatment. HS (7.5%) significantly attenuated water content in the ipsilateral and contralateral hemispheres compared with surgical shams, 0.9% saline, 3% HS, and mannitol treatments. Peak plasma AVP levels were not associated with direct histopathological injury to the anterior hypothalamus. Attenuation of brain water content with 7.5% HS treatment coincides with attenuated serum AVP levels, and we speculate that this may represent one additional mechanism by which osmotherapy attenuates edema associated with ischemic stroke.

Animals↗

PubMed2005

Effect of duration of osmotherapy on blood-brain barrier disruption and regional cerebral edema after experimental stroke.

Osmotherapy is the cornerstone of medical management for cerebral edema associated with large ischemic strokes. We determined the effect of duration of graded increases in serum osmolality with mannitol and hypertonic saline (HS) on blood-brain barrier (BBB) disruption and regional cerebral edema in a well-characterized rat model of large ischemic stroke. Halothane-anesthetized adult male Wistar rats were subjected to transient (2-h) middle cerebral artery occlusion (MCAO) by the intraluminal occlusion technique. Beginning at 6 h after MCAO, rats were treated with either no intravenous fluids or a continuous intravenous infusion (0.3 mL/h) of 0.9% saline, 20% mannitol, 3% HS, or 7.5% HS for 24, 48, 72, and 96 h. In the first series of experiments, BBB permeability was quantified by the Evans blue (EB) extravasation method. In the second series of experiments, water content was assessed by comparing wet-to-dry weight ratios in six predetermined brain regions. Blood-brain barrier disruption was maximal in rats treated with 0.9% saline for 48 h, but did not correlate with increases in serum osmolality or treatment duration with osmotic agents. Treatment with 7.5% HS attenuated water content in the periinfarct regions and all subregions of the contralateral nonischemic hemisphere to a greater extent than mannitol did with no adverse effect on survival rates. These data show that (1) BBB integrity is not affected by the duration and degree of serum osmolality with osmotic agents, and (2) attenuation of increases in brain water content with HS to target levels >350 mOsm/L may have therapeutic implications in the treatment of cerebral edema associated with ischemic stroke.

Animals↗

PubMed2005

Ischemic neuroprotection with selective kappa-opioid receptor agonist is gender specific.

BACKGROUND AND PURPOSE: We demonstrated previously that treatment with selective kappa-opioid receptor (KOR) agonist BRL 52537 hydrochloride [(+/-)-1-(3,4-dichlorophenyl) acetyl-2-(1-pyrrolidinyl) methylpiperidine] (1) has a long therapeutic window for providing ischemic neuroprotection, and (2) attenuates ischemia-evoked NO production in vivo in rats. Neuronally derived NO has been shown to be deleterious in the male but not in the female rodent model of focal ischemic stroke. We tested the hypothesis that BRL provides significant neuroprotection from transient focal ischemia in male but not in female rats. METHODS: Halothane-anesthetized adult male and female Wistar rats (250 to 275 g) were subjected to 2 hours of middle cerebral artery occlusion (MCAO) by the intraluminal suture technique. Adequacy of MCAO and reperfusion was monitored with laser-Doppler flowmetry over the ipsilateral parietal cortex. In the first experiment, male and female rats were treated in a blinded randomized fashion with vehicle saline or 1 mg/kg per hour BRL infusion started at the onset of reperfusion and continued for 22 hours. In the second experiment, ovariectomized (OVX) female rats were treated with vehicle or BRL. Infarct volume in the cortex and caudoputamen (CP) complex was assessed by triphenyl tetrazolium chloride staining at 72 hours after MCAO. RESULTS: Infarct volume (percentage of ipsilateral structure; mean+/-SEM) was attenuated significantly in male rats with BRL treatment (cortex 23+/-5%; CP 44+/-6%; n=15) compared with vehicle-treated male rats (cortex 38+/-4%; CP 66+/-4%; n=15) but not in female rats (BRL-cortex 26+/-6; CP 55+/-8%; vehicle-cortex 26+/-5; CP 62+/-5%; n=10 each). Neurologic deficit score was improved in BRL-treated male rats but not in female rats. Infarct volume was not different in OVX female rats treated with vehicle or BRL. CONCLUSIONS: These data: (1) demonstrate that this dose of selective KOR agonist provides ischemic neuroprotection in male but not female rats, (2) demonstrate that the lack of protection by BRL is not attributable to circulating ovarian hormones, and (3) highlight the importance of using animal models of both sexes in preclinical studies of experimental ischemia.

Animals↗

PubMed2005

Predictors for patterns of brain relapse and overall survival in patients with non-small cell lung cancer.

Our goal was to investigate prognostic factors for different patterns of brain relapse and overall survival so that treatments could be tailored and treatment outcomes improved. We studied 292 patients with non-small cell lung cancer (NSCLC) who had symptomatic, solitary, or multiple brain metastases (isolated or not isolated from extracranial metastases) that had developed early ( 6 months) from initial diagnosis. Factors affecting patterns of relapse and survival were analyzed by univariate and multivariate analyses. Good ECOG performance status (PS) at the time of NSCLC diagnosis was the most important factor that predicted late (rather than early) relapse and improved survival, and was the only factor that predicted isolated brain metastases. Patients whose lungs showed a complete response (CR) to treatment had a higher rate of late brain relapses than non-responders (NR) did (67.3% vs. 7.8%, P<0.001). CR patients also experienced a longer median overall survival than NR patients. Patients with late brain relapses showed better median survival times (18 months vs. 4 months, P<0.0001) than patients with early relapses, and this was an independent factor by Cox regression analysis. Our findings provide a justification for enrolling patients with good PS and controlled lung lesions into clinical trials for the prevention of early, non-isolated brain relapse. More aggressive therapeutic approaches should be applied to patients with late, isolated and solitary relapses to improve both quality and quantity of life.

Adult↗

PubMed2005

Dose-finding and phase 2 study of weekly paclitaxel (taxol) and cisplatin combination in treating Chinese patients with advanced nonsmall cell lung cancer.

OBJECTIVES: The aim of the present study is to evaluate the efficacy and toxicity of weekly paclitaxel combined with cisplatin as first-line chemotherapy in patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) and to identify the optimal dose of weekly paclitaxel to be administered safely and effectively. METHODS: Chemonaive patients with NSCLC, stage 3B with malignant pleural effusion, or stage 4 were enrolled in this study. In the dose-finding study, patients took paclitaxel once weekly at an initial dose of 50 mg/m2 and 3 weeks followed by cisplatin on day 15 at a fixed dose of 80 mg/m2. The escalating dose for paclitaxel was 10mg/m2 for each level. In the phase 2 study, patients received paclitaxel at maximum tolerated dose (MTD). RESULTS: The MTD for paclitaxel was 60 mg/m2. Of the 47 eligible patients, 7 patients had a complete response and 15 achieved a partial response. The overall response was 46.8% (95% CI, 32.0% to 61.6%). The median survival was 16 months (95% CI, 13.4 to 18.6 months). Twenty-four patients (51.1%) completed 6 cycles of treatment. With regard to hematological toxicity, although grade 3/4 neutropenia was observed in 5 patients (10.6%), there was no febrile neutropenia. The major nonhematological toxicity was asthenia, which was observed in all patients (17 patients grade 1/2 and 30 patients with grade 3/4). CONCLUSIONS: Weekly paclitaxel combined with cisplatin on day 15 is a safe and effective regimen as a first-line chemotherapy in NSCLC. The MTD for this regimen was 60 mg/m.

Adult↗

PubMed2005

Airway obstruction by a metastatic mediastinal tumor during anesthesia.

A case of low back pain syndrome was diagnosed due to spinal metastasis with unknown primary origin. During anesthesia for surgical stabilization, unexpected airway obstruction occurred after endotracheal intubation. Fiber-optic bronchoscopic examination showed narrowing of the trachea and main bronchi caused by extrinsic compression. After administration of neostigmine to reverse neuromuscular blockade, the patient resumed spontaneous breath. Airway obstruction was relieved thereafter. The extrinsic lesion was diagnosed as mediastinal lung cancer. The mechanism and management of this airway compromise caused by mediastinal tumor is discussed.

Adult↗

PubMed2005

Blockade of spinal nitric oxide synthase on blood pressure variability and hepatic microcirculation.

BACKGROUND: We previously demonstrated that intrathecal administration of N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, increased systemic arterial blood pressure in a dose-dependent manner in rats. The aim of the study was to investigate the participation of autonomic nervous system on L-NAME-induced hypertension and also illuminate its effects on hepatic microcirculation in rats. METHODS: Eight Spraque-Dawley rats were used and initially anesthetized with ketamine 120 mg/kg, intraperitoneally supplemented by intravenous infusion of ketamine at 30 mg/kg/h for maintenance. Surgical preparations included cannulations of right femoral artery and vein to obtain systemic arterial pressure signals and administer anesthetic drug. A mini-laparotomy was made to facilitate the insertion of a microdialysis probe and attachment of a laser Doppler probe to the middle lobe of the liver. On experiment, L-NAME was administered via the previously placed intrathecal catheter at 0, 0.37, 0.74, and 1.48 micromol in sequence at a 2-h interval. RESULTS: The results showed that the arterial blood pressure increased in a dose-dependent manner. By the same token, the power density of very low frequency (VLF) also increased. The low frequency (LF): high frequency (HF) ratio shifted toward parasympathetic dominance. Blood flow to the liver was unchanged except slightly decreased in the animals receiving 0.37 micromol. The levels of monoethylglycinexylidide (MEGX), an index of hepatic metabolism, were unchanged throughout the experiment. CONCLUSIONS: We concluded that the blockade of spinal nitric oxide synthase by intrathecal administration of L-NAME significantly increased vasomotor tone in a dose-dependent manner and as a consequence induced a reflex sympathetic inhibition. Hepatic microcirculation was stable with the applied doses.

Animals↗

PubMed2005

Adenoid cystic carcinoma of the trachea: a report of seven cases and literature review.

BACKGROUND: Adenoid cystic carcinoma (ACC) of the trachea is rare. The clinical manifestations, natural history, and responses to therapy differ from those of other malignant tracheal tumors. METHOD: In this retrospective study, we examined pathological records of patients in the Department of Pathology at Chang Gung Memorial Hospital from 1990 through 2002. There were five male patients and two female patients with ages that ranged from 21 to 55 years. For these seven patients the clinical manifestations and period from initial symptoms to diagnosis, treatment and outcome are presented. RESULTS: Hemoptysis, nonproductive cough, dyspnea, chest pain and weight loss were the frequent early manifestations. Five patients had tumors in the lower area of the trachea, two had tumors in the upper area of the trachea. In a patient with the tumor in the upper area of the trachea, the tumor involved the cricoid ring, larynx, and subglottic area. In one patient with the tumor in the lower area of the trachea, the tumor invaded the right lower lobe of the lung. The longest survival time was more than 10 years. CONCLUSIONS: ACC is a rare primary tracheal malignancy. The time from first symptoms to diagnosis varied, ranging from weeks to more than 1 year. Complete surgical resection provides the patient with the best chance of prolonged survival or even complete remission.

Adult↗

PubMed2005

Homozygous deletion genotype of angiotensin converting enzyme confers protection against migraine in man.

Studies have shown that migraine may have a major genetic component. Meanwhile, angiotensin converting enzyme (ACE) gene has been implicated as a genetic factor associated with migraine. We designed a case-control study to investigate the association between ACE and migraine in 240 migraine patients and 200 healthy controls, matched by age and sex. There was no significant difference in allelic frequency (I and D) and genotype polymorphism (DD, DI and II) of the ACE gene in migraine patients and controls. Analysis of the difference in ACE polymorphism stratified by gender revealed that male migraine patients with the homozygote DD genotype (ACE-DD) were significantly fewer than that of male controls (OR = 0.331, p = 0.045). There was no existence of a difference among the frequency and duration of headache in each subgroup of migraine patients stratified by ACE genotype. Our findings indicate that ACE-DD may have a slight protective effect against migraine in male patients.

Adolescent↗

PubMed2004

Platelet glycoprotein Ia C807T, Ib C3550T, and IIIa Pl(A1/A2) polymorphisms and ischemic stroke in young Taiwanese.

Platelet plays a pivotal role in the pathogenesis of thrombotic cardiovascular diseases. Recently, the polymorphism of platelet glycoprotein (GP) genes has been reported to be associated with an increased risk for ischemic stroke. The purpose of this study is to evaluate the association between platelet GP genetic variants and ischemic stroke in young Taiwanese. We conducted a case-control study in 157 young ischemic stroke patients recruited between September 2001 and March 2003 and 157 age- and sex-matched controls. The genotypes of platelet GP Ia C807T, GP Ib C3550T, and GP IIIa Pl(A1/A2) polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Student's t-test, chi-square test, and logistic regression modeling were used for data analyses. The GP Ia C807T CC, CT and TT genotype frequencies were similar between patients (50.3%, 43.9%, 5.7%) and controls (53.5%, 38.9%, 7.6%; p=0.58). There were no significant differences in GP Ib C3550T CC and CT genotype distributions between patients (91.1%, 8.9%) and controls (91.7%, 8.3%; p=0.84). Of all subjects, none carries GP IIIa Pl(A2) mutation. In conclusion, platelet GP Ia C807T and GP Ib C3550T polymorphisms in our population are less common compared with Caucasians, and GP IIIa Pl(A1/A2) genetic mutation is not found, and all of them are not associated with ischemic stroke in young Taiwanese.

Adolescent↗

PubMed2004

Community-based multiple screening model: design, implementation, and analysis of 42,387 participants.

BACKGROUND: Multiple disease screening may have several advantages over single disease screening because of the economics of scale, with the high yield of detecting asymptomatic diseases, the identification of multiple diseases or risk factors simultaneously, the enhancement of the attendance rate, and the efficiency of follow-up. METHODS: An integrated model of community-based multiple screening was designed and conducted between 1999 and 2001 in Keelung, Taiwan. The authors used a Papanicolaou (Pap) smear screening program as a base to integrate other screening regimens encompassing four other neoplastic diseases and three nonneoplastic chronic diseases. Screening methods, the interscreening interval, and the follow-up for each screening regimen were designed based on evidence-based literature and current national screening policy. RESULTS: A total of 42,387 subjects participated in the screening activities. A 25% increase in the attendance rate for Pap smear screening was demonstrated after the introduction of multiple disease screening programs. At the first screen, this program yielded a total of 677 asymptomatic neoplasms (16.0 per 1000), including a large proportion of precancerous lesions and small presymptomatic tumors without lymph node involvement. The association between the occurrence of neoplasm and the presence of comorbid nonneoplastic chronic disease was found to be statistically significant (odds ratio, 1.64; 95% confidence interval, 1.38-1.94 [P < 0.05]). The authors also identified 5314 subjects with metabolic syndrome who were at a greater risk for colorectal and oral neoplasias. CONCLUSIONS: The results of the current study demonstrate that an outreach and community-based multiple screening program not only enhances attendance rates but also has a high yield of early cases of various diseases simultaneously, and provides a natural opportunity to elucidate the correlation between neoplastic disease and nonneoplastic chronic disease.

Adult↗

PubMed2004

Increased risk of developing hepatocellular carcinoma associated with carriage of the TNF2 allele of the -308 tumor necrosis factor-alpha promoter gene.

BACKGROUND AND AIMS: Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that may act as an endogenous tumor promoter. A genetic polymorphism of TNF-alpha at position -308 of the promoter region, which includes TNF1 (-308G) and TNF2 (-308A) alleles, has been found to be associated with susceptibility to various types of cancer. We conducted a study to evaluate the association between this polymorphism and hepatocellular carcinoma (HCC). METHODS: We recruited 74 HCC patients and 289 healthy controls, and determined their -308 TNF-alpha promoter genotypes through polymerase chain reaction followed by electrophoresis. RESULTS: Carriage of the TNF2 allele was associated with an increased risk of HCC (odds ratio [OR] = 3.5; 95% confidence interval [CI]:[2.1, 6.0]), and a trend toward a significant increase in the risk of developing HCC was observed from TNF1/TNF1, TNF1/TNF2, to TNF2/TNF2 genotypes (p < 0.01). After adjustment for gender, age, and markers of hepatitis B and C, the OR of developing HCC associated with TNF2 allele carriage was 5.3 (95% CI: [2.3, 12.1]; p < 0.01) CONCLUSIONS: Carriage of the TNF2 allele is a significant predictor of HCC independent of hepatitis B and C, and therefore it may be used as a biomarker for susceptibility to HCC.

Adult↗

PubMed2004

Constitutive expression of a chromosomal class A (BJM group 2) beta-lactamase in Xanthomonas campestris.

Sequencing of the upstream region of the beta-lactamase gene from Xanthomonas campestris pv. campestris 11 (bla(XCC-1)) revealed the cognate ampR1 gene (289 amino acids, 31 kDa). It runs divergently from bla(XCC-1) with a 100-bp intergenic region (IG) containing partially overlapped promoters with structural features typical of the bla-ampR IG. The deduced AmpR1 protein shows significant identity in amino acid sequence and conserved motifs with AmpR proteins of other species, e.g., of Pseudomonas aeruginosa (58.2% amino acid identity). Results of insertional mutation, complementation tests, and beta-lactamase assays suggested that expression of bla(XCC-1) was constitutive and dependent on AmpR1. Four bla genes and two ampR genes are present in the fully sequenced X. campestris pv. campestris ATCC 33913 genome, with XCC3039 and XCC3040 considered the analogues of bla(XCC-1) and ampR1, respectively. An ampR1 homologue was detected by Southern hybridization in the ampicillin-resistant Xanthomonas strains, which appear to express beta-lactamase constitutively. Although the significance remains to be studied, constitutive expression of beta-lactamase by a widespread bacterial genus raises environmental concerns regarding the dissemination of resistance genes.

Ampicillin Resistance↗