Association between leukoaraiosis and cerebral blood flow territory alteration in asymptomatic internal carotid artery stenosis.

AIM: To test the hypothesis that leukoaraiosis (also known as white matter lesion) is associated with cerebral blood flow territory change as revealed by territorial arterial spin-labeling (TASL) magnetic resonance imaging (MRI) in patients with asymptomatic internal carotid artery stenosis (aICAS). MATERIALS AND METHODS: The institutional review board approved this study. Thirty-three patients with aICAS were included prospectively and divided into high-grade (ultrasonographic stenosis ≥70%, n=17) and low-grade (n=16) groups; 16 healthy subjects were also included. Cerebral flow territory was delineated for left ICA, right ICA, and vertebral arteries using TASL MRI and fuzzy clustering. Two licensed neuroradiologists independently and dichotomously rated the hemispherical asymmetry of flow territories. Flow territories were finalised by consensus, and when asymmetry was present, these were divided into normal and abnormal areas where the raters separately assessed leukoaraiosis based on fluid-attenuated inversion recovery images and the Fazekas scale. RESULTS: The inter-rater agreement in the evaluation of flow territory asymmetry with TASL imaging in conjunction with time-of-flight angiogram is substantial (Cohen's kappa=0.82). Multinomial logistic regression (reference group=healthy subjects) indicates that global leukoaraiosis is not a predictor of aICAS after controlling for age, whereas in high-grade patients, the deep white matter lesion is more severe in the area receiving collateral circulation than in the area with normal flow territory (Wilcoxon signed-rank test, p=0.03). CONCLUSION: TASL MRI is clinically feasible in aICAS and shows that more severe deep white matter lesions are associated with collateral circulation in high-grade patients.

Loss of labelling efficiency caused by carotid stent in pseudocontinuous arterial spin labelling perfusion study.

AIM: To elucidate the cause of cerebral hypoperfusion on the stent placement side after carotid artery stent placement (CAS) measured by pseudocontinuous arterial spin labelling (PCASL) perfusion imaging. MATERIALS AND METHODS: Consecutive patients with symptomatic internal carotid artery stenosis receiving CAS were included in the study. Cerebral blood flow (CBF) was measured by PCASL perfusion imaging at 3 T magnetic resonance imaging (MRI) the day before and 3 days after the procedure. Changes in cerebral haemodynamics after CAS were assessed. RESULTS: Twenty-two patients were included; 17 patients had increased or stationary CBF after CAS and five patients had significantly reduced CBF on the stenting side after CAS whereas CBF increased on the contralateral side. High stent position was noticed in the five patients. After labelling plane adjustment to avoid labelling on the stent, no more cerebral hypoperfusion was noticed. CONCLUSION: When using PCASL perfusion imaging to monitor post-stenting CBF, the stent may cause an artefact that leads to a low CBF in the territory of the stented vessel. Routinely adding a fast T2 star gradient-echo echo-planar-imaging covering the upper neck region before PCASL perfusion imaging to identify the stent position and avoid the stent-related artefact is recommended.

Impact of socioeconomic status on vision-related quality of life in primary open-angle glaucoma.

PurposeTo investigate the impact of socioeconomic status (SES) on vision-related quality of life (VRQOL) in patients with primary open-angle glaucoma (POAG).Patients and methodsThis prospective cross-sectional study included consecutive patients with POAG at a tertiary hospital between March 2012 and January 2013. All patients had visual acuity no worse than 20/60 in the better eye and reliable visual field tests. VRQOL was assessed by the validated Taiwan version 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25). Sociodemographic characteristics, medical history, and ocular parameters were recorded. SES was evaluated based on educational attainment and monthly income, both stratified into three levels. Analysis of variance and linear regression analysis were used to evaluate the relationship between SES, VRQOL, and clinical parameters.ResultsAmong the 186 patients recruited, intergroup differences were not observed among educational or monthly income levels for binocular vision or integrated visual field defects. Patients of lower educational and monthly income levels had lower self-reported general health ratings. After adjustment for visual function, treatment complexity, and general health in the multiple linear regression model, patients with a college degree or higher reported better NEI VFQ-25 scores for the composite score (P=0.041), mental health (P=0.035), and peripheral vision (P=0.05) than did those with education below junior high school. Monthly income levels did not affect the NEI VFQ-25 scores.ConclusionEducational attainment significantly affects VRQOL in patients with POAG. Additional counseling may be provided to patients with lower educational background to help them cope with the disease.

Genetic polymorphisms of CYP2E1, GSTM1, and GSTT1; environmental factors and risk of oral cancer.

Both genetic and environmental factors are involved in the development of cancer; some phase I and II enzymes involved in the metabolism of carcinogens are polymorphic in genotypes. This case-control study focused on the interactions between oral cancer risk factors and genetic polymorphisms of cytochrome P-450 (CYP) 2E1 and glutathione S-transferase (GST) M1 and GSTT1. A total of 41 male oral cancer cases was recruited from National Taiwan University Hospital, and 123 healthy controls frequency-matched on ethnicity, sex, and age were recruited from residents living in Taipei City and Taipei County. History of cigarette smoking, alcohol drinking, and betel quid chewing was obtained through a standardized questionnaire interview, and genotypes of CYP2E1, GSTM1, and GSTT1 were determined by PCR. Cigarette smoking, alcohol drinking, and betel quid chewing were significantly associated with the risk of oral cancer in a dose-response relationship. All betel quid chewers smoked cigarettes in both the case and control groups. In the multiple logistic regression analysis, those who had null genotypes of GSTM1 and/or GSTT1 had an increased oral cancer risk compared with those who had non-null genotypes of both GSTM1 and GSTT1, showing a multivariate-adjusted odds ratio (OR) of 4.6 with a 95% confidence interval (CI) of 0.9-23.7 (P = 0.08). The CYP2E1 c1/c2 and c2/c2 genotypes were associated with a significantly increased oral cancer risk compared with the c1/c1 genotype among those who did not chew betel quid (OR, 4.7; 95% CI, 1.1-20.2), but not among betel quid chewers. Habitual alcohol drinking was associated with a significantly increased oral cancer risk, showing an OR of 3.0 (95% CI, 1.1-8.8). These results implied that there are gene-gene and gene-environment interactions in the development of oral cancer.

Association between genetic polymorphism of tumor necrosis factor-alpha and risk of oral submucous fibrosis, a pre-cancerous condition of oral cancer.

Many cytokines have been thought to play important roles in the pathogenesis of oral submucous fibrosis (OSF), an areca nut chewing-specific pre-cancerous condition characterized by the deposition of collagen in oral submucosa. Tumor necrosis factor-alpha (TNF-alpha), situated in the class III region of human leukocyte antigen (HLA), is a mediator with multiple functions, including the regulation of inflammatory reaction and transcriptions of collagen and collagenase. In total, 809 male subjects were recruited for assessment of the association of OSF with a bi-allelic promoter-region (-308) polymorphism on the TNFA gene. The high production allele, TNF2, was significantly lower among OSF subjects (n = 166) than in areca-chewing controls (n = 284). This association was independent of oral cancer status. The multivariate-adjusted odds ratio for the TNFA 11 genotype was 2.6 (95% confidence interval = 1.4-4.9; p = 0.004). The finding may imply a multifunctional etiological factor of TNF-alpha in OSF pathogenesis.

Induction of the c-jun protooncogene expression by areca nut extract and arecoline on oral mucosal fibroblasts.

To investigate the mechanisms of areca quid (AQ)-induced carcinogenesis, expression of c-fos and c-jun protooncogenes was examined in human oral mucosal fibroblasts after exposure to areca nut extracts (ANE) or arecoline. We found that treatment of cells with 200 microg/ml ANE or 10 microg/ml arecoline for 1 h induced about three-fold increase in c-jun mRNA levels. This increase was transient and the level of c-jun mRNAs returned rapidly to control levels thereafter. However, ANE and arecoline did not induce c-fos mRNA expression at detectable levels. During AQ chewing, oral mucosal cells are continuously stimulated by ANE and arecoline. Persistent induction of the c-jun protooncogene by ANE and arecoline may be one of the mechanisms in the carcinogenesis of oral squamous cell carcinoma in Taiwan. Furthermore, we observed that pre-incubation of cells with either N-acetyl-cysteine [a glutathione (GSH) precursor] or L-buthionine-S,R-sulfoximine (a specific inhibitor of GSH biosynthesis) had a minimal effect on arecoline-induced c-jun expression. Therefore, arecoline-induced c-jun expression is independent of GSH depletion.

Diagnosis of oral cancer by light-induced autofluorescence spectroscopy using double excitation wavelengths.

A cancer diagnostic algorithm, light-induced autofluorescence spectroscopy using double excitations wavelengths, was employed for distinguishing between cancerous and normal oral mucosa. For emission spectra at the shorter excitation wavelengths (280, 290, and 300 nm), the ratio between the area under 325-335 nm and the area under 465-475 nm was calculated. In the same way, for emission spectra at the longer excitation wavelengths (320, 330, and 340 nm), the ratio between the area under 375-385 nm and the area under 465-475 nm was calculated. Receiver operating characteristic curves were used to evaluate the performance of algorithms using single and the double (by combining shorter and longer) excitation wavelengths. The results showed that better performance, up to sensitivity 81.25%, specificity 93.75%, and positive predictive value 92.86%, could be achieved by using the double excitation wavelengths. The present study can be useful as a basis for further investigation on in vivo autofluorescence measurement and analysis using double excitation wavelength.

Verruciform xanthoma. Case report and literature review.

Verruciform xanthoma is a relatively uncommon lesion. Half of the reported cases occurred in the gingiva or alveolar ridge. In most cases, the clinical impressions are papilloma or verrucous carcinoma, which demonstrates the importance of the clinical and pathological recognition of this lesion. The cause of pathogenesis is still unknown since the first report in 1971. There are some cases reported in conjunction with leukoplakia, carcinoma in situ, pemphigus, and discoid lupus erythematosus (DLE), which merits close evaluation of this disease. This article reports two cases of verruciform xanthoma and reviews the evidence of its pathogenesis from the available literature.

Arecoline cytotoxicity on human oral mucosal fibroblasts related to cellular thiol and esterase activities.

Betel quid (BQ) chewing is associated with an increased risk of oral submucous fibrosis (OSF) and oral cancer in India and many south-east Asian countries. Recently, we have shown that arecoline is cytotoxic to cultured human oral mucosal fibroblasts. This study investigated protective effects of various agents against the cytotoxicity of arecoline and its mechanisms. Arecoline, at concentrations of 0.2 and 0.4 mM, decreased the cell numbers by 38% and 63%, respectively. At a concentration of 2 mM, N-acetyl-L-cysteine [a glutathione (GSH) synthesis precursor] could prevent arecoline-induced cytotoxicity. The decrease in cell numbers was reduced to 17% relative to control. Extracellular addition of esterase at a concentration of 0.1 U/ml could almost completely protect the oral mucosal fibroblast (OMF) from arecoline-induced cytotoxicity. Arecoline is a muscarinic receptor agonist. However, atropine, a muscarinic receptor antagonist was unable to protect the cells from arecoline cytotoxicity at a concentration of 10 microM. Pretreatment of OMF with 50 microM buthionine sulfoximine (a cellular GSH synthesis inhibitor) or 0.5 mM diethylmaleate (a cellular GSH depleting agent) potentiated the cytotoxic effects of arecoline. These results indicate that cytotoxicity of arecoline on OMF is associated with cellular GSH levels and esterase activities. Factors that induce the GSH synthesis or esterase activity of oral mucosal cells can be used for future chemoprevention of BQ chewing-related lesions.

Acute pulmonary oedema following administration of vasopressin for control of massive GI tract haemorrhage in a major burn patient.

A 35-year-old male sustained a full-skin thickness chemical burn involving 60 per cent of TBSA when hydrochloric acid was applied to his face, trunk and extremities by his girlfriend. Debridements and skin graftings were performed smoothly and he was doing well until day 23 after injury, when massive GI tract bleeding caused a drop in blood pressure. Vasopressin was given intravenously to control the bleeding, which stopped, and the blood pressure returned to normal after transfusion. After the vasopressin infusion was tapered off acute pulmonary oedema developed abruptly, which required treatment by intubation and PEEP using a respirator. The lung condition had returned to normal by the following day. A second episode of massive GI tract bleeding recurred 10 days later, again vasopressin was given through a catheter into the inferior mesenteric artery. Again pulmonary oedema developed 38 h after the vasopressin use, the oedema disappeared within 2 days when the vasopressin infusion tapered off. It should be kept in mind that acute pulmonary oedema may develop when high doses of vasopressin are used in the treatment of Curling's ulcer or other GI tract bleeding.

Repair of oroantral communications in the third molar region by random palatal flap.

Various palatal flap procedures based on the greater palatine vessels have been advocated for the repair of oroantral communications (OACs). However, when the defect is located in the third molar region, difficulty is encountered in using the palatal flap because rotation is hindered by the vascular pedicle. In this study, we used random palatal flaps to repair OACs in the third molar area in 21 patients. The vascular pedicles were ligated and severed in all cases in order to evaluate whether it was necessary to preserve the greater palatine vessels when using the palatal rotation flap (PRF). The repair was successful in 16 cases (76.2%). The length/width ratio of the flap was the most important factor determining the outcome. The ratios were 2.23 +/- 0.12 and 2.40 +/- 0.14 in the success and failure groups, respectively and their difference was statistically significant (P<0.05). Other clinical parameters such as age, gender, antral infection, tooth displacement into the sinus and duration of the communication had no influence on the outcome (P>0.05). The study showed that the PRF with the appropriate length/width ratio can safely be used in a random fashion. This provided another option in the repair of oroantral communications of difficult locations such as in the tuberosity area.

Comparison of calcium phosphate cement mixture and pure calcium hydroxide as direct pulp-capping agents.

Calcium phosphate cement (CPC) and pure calcium hydroxide were used as direct pulp-capping agents on the deliberately exposed pulp tissue of 60 teeth in five monkeys. Their effects on the pulp tissue of individual teeth were observed and histologically compared after 12, 20 and 24 weeks. The results showed that both materials produced similar responses with regard to their biocompatibility and induction of hard tissue barrier formation. Vasodilatation, chronic inflammation and calcification nidi scattered within the pulp tissue of the 12-week group were observed. Twenty weeks after application of capping materials, a crude reparative dentinal bridge with inclusion of soft tissue or bulky capping agents appeared. A more mature, hard tissue barrier with a better degree of mineralization and formation of dentinal tubules was demonstrated in the 24-week group. The above findings associated with the abilities of self-setting and fair compressive strength suggest that CPC appears superior to pure calcium hydroxide and may have potential for clinical application, although many issues remain to be further investigated.

Pregnancy following oocyte donation and tubal embryo transfer in patients with premature ovarian failure: report of two cases.

Two pregnancies in patients with premature ovarian failure utilizing donated oocytes, in-vitro fertilization (IVF) and tubal embryo transfer (TET), are reported. The recipients received cyclic hormone replacement therapy for six months to prepare the endometrium for implantation. An evaluation cycle was tested to document that the hormone milieu established by the hormone replacement protocol was similar to that of a natural ovulatory cycle. During the oocyte donation cycle, the recipient received incremental estrogen replacement treatment of flexible length during the follicular phase of the donor's stimulated cycle to synchronize the recipient's endometrium to the donor's embryo. Concurrently, the donor underwent controlled ovarian hyperstimulation and transvaginal ultrasound-guided oocyte retrieval. After fertilization of the donated oocytes with sperm from the recipient's husband and cleavage of the fertilized oocytes into the 2- to 4-cell stage, laparoscopic embryo transfer into the recipient's fallopian tube was performed. Case 1 received 4 embryos by the TET procedure. Pregnancy was confirmed by visualization of a gestational sac in the uterine cavity 3 weeks after TET, but miscarriage occurred at the tenth gestational week. In Case 2, the pregnancy was established after TET of 2 embryos. Estrogen and progesterone supplements were maintained until day 100 after TET. The patient delivered a healthy male baby, weighing 2,520 g at 38 weeks of gestation.

How often should a port-A-cath be flushed?

While it is important during treatment to flush the port-A-cath (PAC) with heparin regularly, catheter maintenance needs to be evaluated in those patients who, after completion of therapy, retained their ports for extended periods of time. The manufacturer has recommended monthly accession to maintain catheter patency and function. Our objective is to demonstrate that a longer interval between maintenance accessions of PACs still may be medically safe, convenient, and more efficient. We performed a retrospective review of all patients who had undergone PAC insertion from 1988 to 1993 at the Albert Einstein College of Medicine, and from 1997 to 2002 at the New York Hospital Medical Center of Queens. An adequate maintenance time is defined as a period of at least 6 months without chemotherapy or total parenteral nutrition. Data collected included date and location of PAC insertion, date of PAC accessions, PAC complications, and results of attempts at flushing the catheters with no venous blood return. All data were entered into an Excel spreadsheet and analyzed. The difference in interval accessions in patients without any complication to patients with complication was calculated using the Mann-Whitney "U" test. A total of 73 patients were included in the study. Compliance with visits for PAC maintenance varied considerably with the individual median accession times varying between 28 and 262 days with an overall median of 42 days. The individual means ranged from 29.5 to 244 days with an overall mean of 53.6 days. Seven patients in the group had episodes where the provider was unable to draw blood from the port during routine accession. The average intervals between accessions for each of these patients ranged from 38 to 244 days. The average intervals of accession among those patients who had no blood return during PAC accession was 79 days, versus 63 days for those without any difficulty. The difference was not statistically significant (p>0.05). Monthly maintenance of PAC is excessive, inconvenient for the patients, and expensive. Extending the interval of PAC maintenance proves to be medically safe and beneficial to the patients, the physicians and the health care system. Our clinical experience suggests that less frequent accessions of PACs is safe and feasible. We strongly advocate future prospective investigation of alternative PAC maintenance protocols in gynecologic cancer patients.

Evaluation of MMA-4-META-TBB resin as a dental adhesive material.

A new adhesive resin containing a reactive monomer, 4-methacryloxyethyl trimellitate anhydride (4-META) was prepared, and its application to hard tooth tissues and metals was studied. Scanning electron microscopy showed that the average length of 4-META resin tags in enamel and dentin was 22 mu and 40 mu respectively. The tensile adhesive strength between 4-META resin and enamel was about 130 kg/cm2 after etching with 65% phosphoric acid. Its bond strength to dentin treated with a cleaning solution of 10% citric acid and 3% ferric chloride was about 190 kg/cm2. In precious alloys heated at 500 degrees C for 5-10 minutes, a bond strength of more than 100 kg/cm2 was obtained. The precious alloys containing Au, Ag, Pt and Cu should be selected especially for dental restorations. In polished non-precious alloys, the bond strength was greater than 100 kg/cm2. If non-precious alloys were oxidized with HNO3, the bond strength increased to 150-200 kg/cm2. The results suggest that the nickel-chromium alloy used in fixed prosthodontics must be treated chemically before adhesion with 4-META resin, but cobalt-chromium alloy used in removable partial dentures bonds well with 4-META resin without chemical treatment. In conclusion, MMA-4-META-TBB resin seems to be a promising adhesive material in dentistry.

Biocompatibility of polysulfone composite materials for dental implant.

As a part of the work designed to find a material suitable for a dental implant, tissue reaction of various kinds of polysulfone composite materials has first been studied by implantation in the femur of rats and in the mandible of rabbits. Histological examination showed that the porous polysulfone composite containing 20 wt.% of tricalcium phosphate exhibited a favorable osteogenesis. The tooth replica implants made of this composite material were inserted into the extraction sockets of dogs. During 5.5 months of observation, horizontal or diagonal orientation of periodontal fibers, no epithelization, and no alveolar bone resorption were noted. This study suggests a promising feasibility of the polysulfone-calcium phosphate composite material as a dental implant material.

Evaluation of polysulfone as a potential biomedical material.

In the course of preliminary screening of various potential biomaterials, polysulfone (PS) has been found to have good biocompatibility (1,2). This paper describes the detailed results of evaluation of PS by several methods. Although a number of screening programs for biomaterials have been published (3,4,5,6,), we used our own program in this experiment.

Loss of heterozygosity of APC and MCC genes in oral squamous cell carcinomas in Taiwan.

Loss of heterozygosity (LOH) at adenomatous polyposis coli (APC) and mutated in colon cancer (MCC) genes was investigated in 37 untreated human primary oral squamous cell carcinomas (SCCs) using the polymerase chain reaction. LOH was observed in 14 of 26 (53.8%) heterozygous (informative) patients at APC and 9 of 13 (69.2%) heterozygous patients at MCC> Homozygous deletion of MCC was detected in one patient. Of the 37 patients, 29 were informative at APC or MCC or both; LOH at APC and/or MCC was detected in 68.9% (20/29) of the cases. Ten cases were informative for both genes; LOH at both loci was found in only three of these cases. LOH at the APC and/or MCC was found in both early and advanced stages of oral SCCs. No significant correlation was observed between LOH at the APC and/or MCC locus and the patients' tobacco/betel quid consumption, tumour location, TNM status, or histological differentiation. These results suggest that LOH at the APC and/or MCC may be an early event and may play a role in the pathogenesis of human oral SCCs in Taiwan.

Cytotoxic and cytostatic effects of arecoline on oral mucosal fibroblasts.

Betel quid (BQ) chewing shows strong correlation to the incidence of oral submucous fibrosis and oral cancer in Taiwan. Arecoline, the main areca alkaloid, is considered to be one of the etiologic factors in BQ. To elucidate the role(s) of arecoline in the pathogenesis of BQ chewing related oral mucosal lesions, we used oral mucosal fibroblasts to study the effects of serum concentration, cell density, and incubation time on the cytotoxic response to arecoline. At a concentration less than 0.2 mM, arecoline was not cytotoxic to oral mucosal cells after 1, 3, and 6 days of incubation. After 3 days of incubation, the cytotoxic and cytostatic effects of arecoline became evident when the cells were exposed to higher concentrations of arecoline (0.2 mM) and serum (10% FCS). Exposure of cells (1 x 10(4) cells/well) to 0.2 mM of arecoline in 0.5% FCS for 3 and 6 days led to a 20% and 23% decrease, respectively, in the cell number, whereas exposure of cells (1 x 10(4) cells/well) to 0.2 mM arecoline in 10% FCS led to a 38% and 53% decrease, respectively, in cell number. At a higher cell density (5 x 10(4) and 1 x 10(5) cells/well), 0.2 mM arecoline led to less cytotoxicity (38% and 21% of decreasing in cell number, respectively) after 6 days of incubation. Our results indicated that arecoline was not mitogenic to oral mucosal fibroblasts, and that the cytotoxic and cytostatic effects of arecoline on oral mucosal fibroblasts could be modulated by the changes in the cell density, serum concentrations, and incubation time.

MDM2 expression in areca quid chewing-associated oral squamous cell carcinomas in Taiwan.

MDM2 (murine double minute gene 2) overexpression has been implicated in the pathogenesis of human tumors via inhibition of the p53 tumor suppressor protein. To investigate the potential involvement of MDM2 overexpression in the pathogenesis of oral squamous cell carcinomas (SCCs) in Taiwan, we examined the expression of MDM2 protein and its relationship to p53 protein levels in 52 oral SCCs using antibodies to MDM2 and p53. Of the 52 patients, 36 (69 %) had tumors with positive MDM2 nuclear staining and 32 (61%) had tumors with p53 nuclear staining. Co-expression of MDM2 protein and p53 was detected in 25 (48%) cases; and 9 (17%) tumors showed neither MDM2 protein nor p53 staining. A significant correlation was observed between MDM2 protein and p53 expression in 38 cases with an areca quid (AQ) chewing habit (P=0.032). No significant correlation was found between the degree of MDM2 protein staining and the patients' ages, sex, cancer location, clinical staging, primary tumor TNM status or histological differentiation of SCC at the time of initial presentation. Kaplan-Meier analysis showed that either MDM2 protein expression or co-expression of p53 and MDM2 protein did not relate significantly to patient overall survival. Nevertheless, the high prevalence of MDM2 protein overexpression found in this study suggest that MDM2 may also participate in the carcinogenesis of AQ chewing-associated oral SCCs in Taiwan.