Sjögren's syndrome associated with protein losing gastroenteropathy manifested by intestinal lymphangiectasia successfully treated with prednisolone and hydroxychloroquine.

Protein-losing gastroenteropathy (PLGE), a rare manifestation of primary Sjögren's syndrome (SS), is characterized by profound edema and severe hypoalbuminemia secondary to excessive serum protein loss from the gastrointestinal tract and is clinically indistinguishable from nephrotic syndrome. We report a case of a 30-year-old Taiwanese woman with PLGE-associated SS. In addition to a positive Schirmer's test, she had eye-dryness, thirst, and high levels of anti-SSA antibodies, fulfilling SS criteria. PLGE diagnosis was highly appropriate given the clinical profile of hypoalbuminemia, hypercholesterolemia, pleural effusion, and ascites, with absent cardiac, hepatic, or renal disease. We were unable to perform technetium-99 m-labeled human serum albumin scintigraphy ((99m)Tc-HAS). However, the patient's edema and albumin level improved dramatically in response to a 3-month regime of oral prednisolone followed by oral hydroxychloroquine.

The combinatorial effect of different Equex STM paste concentrations, cryoprotectants and the straw-freezing methods on the post-thaw boar semen quality.

This study was to evaluate the combinatorial effect (14 treatments, A-N) of different Equex STM paste concentrations, cryoprotectants and the straw-freezing method on the post-thaw boar semen quality. Two ejaculates were collected from each of nine boars (three boars from each of three breeds). Semen was diluted in extenders with different concentrations of Equex STM paste and different cryoprotectants [glycerol or dimethylacetamide (DMA)] before cryopreserving via liquid nitrogen or dry ice. Motility, viability, percentage of spermatozoa with intense acrosomal staining and with normal morphology of post-thaw sperm were evaluated. The qualities of thawed semen were best preserved in treatment H (extender with 0.5% Equex STM paste and 5% glycerol and freezing by dry ice) and were worst in treatment B (extender with 0% Equex STM paste and 5% DMA and freezing by dry ice). Significant difference (p < 0.05) was present in post-thawed sperm motility (63% vs 27%), sperm viability (70% vs 33%) and sperm acrosomal integrity rate (68% vs 29%) between treatments H and B. However, sperm proportion with normal morphology showed no significant difference among treatments (66% vs 66%; p > 0.05). Moreover, statistical analysis suggests that no significant difference was present in semen quality among breed or individual donors (p > 0.05). These findings suggest that Equex STM paste improved the cryosurvival efficiency of boar sperm, and the favourable straw-freezing method changes between glycerol and DMA.

Association of HPV infections with second primary tumors in early-staged oral cavity cancer.

OBJECTIVE: The infection of human papilloma virus (HPV) has been reported in head and neck cancer; however, the clinical significance of HPV infection on the pathogenesis of oral cavity squamous cell carcinoma (OSCC) is still uncertain. MATERIALS AND METHODS: The study recruited 103 patients with pathological early-stage OSCC between March 1997 and December 2003 from Chang Gung Memorial Hospital, Taiwan. Tumor specimens were HPV-genotyped by the EasychipVR HPV Blot method. Clinical association study was performed by using chi-square, Kaplan-Meier, and logrank tests. RESULTS: Thirty-one patients (30.1%) were positive for HPV infection. The most frequent HPV types were types 16 (16 patients, 51.6%) and 18 (seven patients, 22.6%). HPV infection was not associated with tumor aggressiveness (pathological tumor stage or differentiation status), risk exposure (alcohol, cigarette, or areca quid chewing habit), or the treatment outcome (disease-free survival or overall survival). However, infection with HPV-18 was associated with the occurrence of a second primary cancers (P = 0.033), indicating the infection of HPV in OSCC enhances the susceptibility of developing secondary malignancy. CONCLUSIONS: There are 30% of the patients with OSCC infected with HPV, with most high-risk types. HPV-18 infection may enhance the susceptibility of second primary tumors. Large scale of validation study will be needed to confirm this result.

Preoperative circulating C-reactive protein levels predict pathological aggressiveness in oral squamous cell carcinoma: a retrospective clinical study.

OBJECTIVES: Previous studies have demonstrated a relationship between elevated serum C-reactive protein (CRP) levels and shorter survival in cancer patients. Few studies, however, have investigated the role of serum CRP levels in oral squamous cell carcinoma. The present study was conducted to analyze the relationship between preoperative CRP levels, clinicopathologic factors, and prognosis in oral squamous cell carcinoma patients. DESIGN: Retrospective clinical study. SETTING: University teaching hospital. PARTICIPANTS: Eighteen oral cavity leukoplakia and 59 oral squamous cell carcinoma patients between November 2006 and November 2009 from the Chang Gung Memorial Hospital. OUTCOME MEASURES: Clinicopathologic parameters, disease-free survival and overall survival were correlated with CRP levels. METHODS: Serum CRP levels were measured preoperatively, and all oral cavity cancer patients underwent curative intent radical surgery with or without postoperative adjuvant therapy. RESULTS: The CRP levels in leukoplakia patients were used to analyze if factors (including diabetes and liver cirrhosis, smoking, alcohol drinking and areca quid chewing) influence CRP levels, and the results demonstrated they were not associated with CRP elevation (> 5.0 mg/L) (P > 0.05). In oral cancer patients, elevated CRP levels were associated with tumor status (P = 0.005), tumor stage (P = 0.054), bone invasion (P = 0.033), lymph node metastasis (P = 0.004) and lymph node extra-capsular spread (P = 0.018). Patients with higher CRP levels showed poorer disease-free survival (log rank test, P < 0.001) and overall survival (log rank test, P = 0.013). CONCLUSIONS: Preoperative serum CRP levels are associated with advanced tumor stage, bone invasion, lymph node metastasis, lymph node extra-capsular spread and patients' survival. CRP is thus potentially a prognostic indicator, but studies with longer follow-up will be needed to confirm its reliability.

Sequential detection of Salmonella typhimurium and Bacillus anthracis spores using magnetoelastic biosensors.

Multiple phage-based magnetoelastic (ME) biosensors were simultaneously monitored for the detection of different biological pathogens that were sequentially introduced to the measurement system. The biosensors were formed by immobilizing phage and 1mg/ml BSA (blocking agent) onto the magnetoelastic resonator's surface. The detection system included a reference sensor as a control, an E2 phage-coated sensor specific to S. typhimurium, and a JRB7 phage-coated sensor specific to B. anthracis spores. The sensors were free standing during the test, being held in place by a magnetic field. Upon sequential exposure to single pathogenic solutions, only the biosensor coated with the corresponding specific phage responded. As the cells/spores were captured by the specific phage-coated sensor, the mass of the sensor increased, resulting in a decrease in the sensor's resonance frequency. Additionally, non-specific binding was effectively eliminated by BSA blocking and was verified by the reference sensor, which showed no frequency shift. Scanning electron microscopy was used to visually verify the interaction of each biosensor with its target analyte. The results demonstrate that multiple magnetoelastic sensors may be simultaneously monitored to detect specifically targeted pathogenic species with good selectivity. This research is the first stage of an ongoing effort to simultaneously detect the presence of multiple pathogens in a complex analyte.

A novel unconventional antigen MPD5 elicits anti-tumor humoral immune responses in a subset of patients with polycythemia vera.

In an effort to define the antigenic mechanism that contributes to beneficial therapeutic outcome in patients with polycythemia vera (PV), we screened a human testis cDNA library with serological cloning derived from sera of three PV patients who had undergone therapeutic-induced remission. As a result, we identified a novel antigen, MPD5, which belongs to the group of cryptic antigens with unconventional genomic intron/exon structure. Moreover, MPD5 elicited IgG antibody responses in a subset of PV patients who had benefited from a variety of therapies--including IFN-alpha, Hydroxyurea, Imatinib mesylate, Anagrelide, and phlebotomy--but not in untreated PV patients or healthy donors, suggesting that MPD5 is a PV-associated, therapy-related antigen. In the granulocytes of PV patients who are responsive to therapy, upregulated MPD5 expression may serve to enhance immune responses. These findings provide new insight into the mechanism underlying regulation of the self-antigen repertoire that elicits anti-tumor immune responses in patients with myeloproliferative diseases, indicating the potential of these self-antigens as targets of novel immunotherapy.

New symptomatic compression fracture after percutaneous vertebroplasty at the thoracolumbar junction.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the risk factors for new symptomatic vertebral compression fractures after vertebroplasty at the thoracolumbar junction. MATERIALS AND METHODS: We conducted a retrospective analysis of 53 patients treated with percutaneous vertebroplasty at the thoracolumbar junction (T12, L1). The follow-up period was 15-27 months. The occurrence of new symptomatic vertebral compression fractures was recorded after vertebroplasty. We evaluated patient age and sex, amount of injected cement, vacuum clefts in the collapsed bodies, initial wedge angle of the compression fracture, change of the wedge angle after vertebroplasty, intradiskal cement leak, and percentage of height restoration of the vertebral body. In this report, we surveyed the possible risk factors for new symptomatic vertebral compression fractures. RESULTS: Thirty-nine (74%) of the 53 patients had fluid and/or air in the compression fracture at the thoracolumbar junction (T12, L1). Eight (20.5%) of the 39 patients with vacuum clefts had new symptomatic compression fracture after vertebroplasty between 1 month and 4 days after surgery to 23 months and 4 days after surgery. The patients with new symptomatic compression fracture had higher initial wedge angle and wedge angle change (more than 7 degrees ) after vertebroplasty than those without fractures; these data were considered statistically significant. CONCLUSIONS: The incidence of vacuum clefts in the compression fracture at the thoracolumbar junction is high (74%). The severity of initial wedge angle and wedge angle change affects the incidence of new symptomatic compression fracture.

HLA-A2.1-restricted T cells react to SEREX-defined tumor antigen CML66L and are suppressed by CD4+CD25+ regulatory T cells.

The question of whether T cell responses to SEREX-defined tumor antigens are under regulation of naturally occurring CD4+CD25+ regulatory T cells (nTreg cells) has not been answered. To address this issue, we first identified an HLA-A2.1-restricted T cell antigen epitope of SEREX-identified tumor antigen CML66L, 66Pa. The HLA-A2.1/66Pa peptide complex in vitro stimulated the in vivo-primed T cells as shown by increased T cell proliferation, higher secretion of the T cell cytokine interferon-gamma (IFN-gamma), increased production of intracellular IFN-gamma in CD8+ T cells, and higher T cell-mediated cytotoxicities of CML66L+ human tumor cells. This suggests that CML66L elicits T cell immune responses. We also developed a novel internal reference epitope for identification of T cell epitopes by construction of chimeric CML66L containing myeloid antigen proteinase 3 epitope Pr1 as a control. Finally, we found that nTreg cells regulates T cell responses to 66Pa, and that depletion of nTreg cells via a pro-apoptotic protein Bax-dependent mechanism enhances polyclonal T cell responses to 66Pa. These findings provide new insights into the T cell participation in SEREX-defined anti-tumor immune responses and novel direction in enhancement of anti-leukemia immunotherapy by modulation of homeostasis of nTreg cells.

Processing sites are different in the generation of HLA-A2.1-restricted, T cell reactive tumor antigen epitopes and viral epitopes.

In order to improve the processing efficiency of T cell tumor antigen epitopes, this bioinformatic study compares proteolytic sites in the generation of 47 experimentally identified HLA-A2.1-restricted immunodominant tumor antigen epitopes to those of 52 documented HLA-A2.1-restricted immunodominant viral antigen epitopes. Our results show that the amino acid frequencies in the C-terminal cleavage sites of the tumor antigen epitopes, as well as several positions within the 10 amino acid (aa) flanking regions, are significantly different from those of the viral antigen epitopes. In the 9 amino acid epitope region, frequencies differed somewhat in the secondary-anchored amino acid residues on E3 (the third aa of the epitope), E4, E6, E7 and E8; however, frequencies in the primary-anchored positions, on E2 and E9, for binding in the HLA-A2.1 groove, remained almost identical. The most frequently occurring amino acid pairs in both N-terminal and C-terminal cleavage sites in the generation of tumor antigen epitopes were different from those of the viral antigen epitopes. Our findings demonstrate for the first time that these two groups of epitopes may be cleaved by distinct sets of proteasomes and peptidases or similar enzymes with lower efficiencies for tumor epitopes. In the future, in order to more effectively generate tumor antigen epitopes, targeted activation of the immunoproteasomes and peptidases that mediate the cleavage of viral epitopes could be achieved, thus enhancing our potential for antigen-specific tumor immunotherapy.

The use of the GlideScope for tracheal intubation in patients with ankylosing spondylitis.

BACKGROUND: The GlideScopeVideo Laryngoscope is a new intubating device. The aim of the study was to investigate the use of the GlideScopefor tracheal intubation in patients with ankylosing spondylitis (AS) undergoing general anaesthesia. METHODS: Twenty AS patients were chosen to undergo tracheal intubation by the GlideScope. Preoperative airway assessments were carried out to predict the difficulty of tracheal intubation. Before intubation all patients were given a modified Cormack and Lehane (MCLS) grade and percentage of glottic opening (POGO) score by a separate anaesthetist using a Macintosh size 3 blade. The patients were then intubated, using the GlideScope, by a different anaesthetist during which the larynx was inspected and given another MCLS grade and POGO score. RESULTS: Twelve of the AS patients were judged to have had difficult intubation by preoperative airway assessment. Eleven of the twelve patients had MCLS grades III or IV by direct laryngoscopy and were considered to have had a difficult laryngoscopy. Naso-tracheal intubations by the GlideScope were successful on 17/20 occasions, including 8 of the 11 difficult laryngoscopy. The GlideScope improved the MCLS grade and POGO score in the majority of AS patients compared with direct laryngoscopy (P<0.01). CONCLUSIONS: The GlideScope provides a better laryngoscopic view than that of direct laryngoscopy. Most of the AS patients presenting with MCLS grade III or IV by direct laryngoscopy can be intubated successfully by the GlideScope. In elective patients with AS, awake fibreoptic intubation offers a higher level of security because it can be applied while maintaining spontaneous breathing. The use of GlideScope for tracheal intubation may be an alternative option in these patients who prefer their airway management under anaesthesia.

p53 polymorphisms associated with mutations in and loss of heterozygosity of the p53 gene in male oral squamous cell carcinomas in Taiwan.

The present study was designed to examine whether different p53 haplotypes of exon 4-intron 3-intron 6 affect the frequency of mutations and loss of heterozygosity (LOH) of the p53 gene in male oral squamous cell carcinomas (OSCCs) in Taiwan. We found that individuals without two Pro-W-G alleles had significantly higher frequency of p53 mutations than those with two Pro-W-G alleles (odds ratio (OR) = 1.98; 95% confidence interval (CI), 1.10-3.56). Out of the 172 p53 gene exon 4 informative male OSCCs, 72 (41.9%) showed LOH. Among these 72 OSCCs with LOH, the frequency of Pro allele loss was 73.6% (53/72). It is notable that alcohol drinking increased the frequency of Arg allele loss (OR = 10.56; 95% CI, 1.23-234.94) in OSCCs from patients who both smoked cigarettes and chewed areca quid (AQ). The frequency of LOH of p53 was not different between p53-mutated OSCCs and p53-normal OSCCs. Thus, the present study revealed that (a) the Arg allele is associated with p53 mutations, (b) the Pro allele is preferentially lost in OSCCs associated with cigarette smoking and AQ chewing, while the frequency of Arg allele loss is increased with alcohol drinking, and (c) haploinsufficiency of p53 is in itself likely to contribute to tumour progression in Taiwanese OSCCs.

The role of glottal gap in predicting aspiration in patients with unilateral vocal paralysis.

Aspiration has been frequently noted among patients suffering from vocal-fold paralysis. The association between a defect of glottal closure and aspiration in patients with unilateral vocal paralysis appears to have been rarely reported. The current study reviews collected data consisting of videotaped flexible nasoendoscopy and stroboscopy for patients with a unilateral vocal-fold paralysis. Mean normalized glottal gap areas for patients suffering vocal paralysis with associated aspiration are significant greater than that for the non-aspiration group. Subsequent to the surgical correction of the glottal gap, all patients recovered well from their earlier aspiration. The investigation of objectively derived data revealed that poor airway protection due to incomplete closure of the vocal fold was the major cause of aspiration for patients suffering unilateral vocal-fold paralysis. Intracordal autologous fat injection can successfully improve the breath control and eliminate aspiration in patients with vocal-fold paralysis.

Polymorphism of HLA-B27 in Taiwanese Chinese.

Heterogeneity of HLA-B27 is represented by a family of 24 closely related alleles/subtypes. Frequency and disease association of these alleles with spondyloarthropathies differ among ethnic groups. Accurate investigation of frequencies of alleles is often hindered by the size and demographic region of sample tested. With an ever-increasing number of B27 alleles being discovered, it is becoming imperative to establish disease association of each individual alleles and its biological importance. In a large number of normal healthy Taiwanese Chinese individuals (75,777) tested nationally, over a period of five years, in a single immunogenetics centre, we found additional B27 subtypes not revealed in a previous Taiwanese Chinese population study. The subtypes found in Taiwanese Chinese and the frequencies of each of the subtypes are reported.

Prognostic significance of EGFR and Her-2 in oral cavity cancer in betel quid prevalent area cancer prognosis.

Although several studies have found overexpression of epidermal growth factor receptor (EGFR) proteins EGFR and Her-2 in head and neck cancers, the clinical relevance of the finding varies. We examined the expression and clinical association of these molecules with oral squamous cell carcinoma in an area where betel chewing is prevalent. EGFR and Her-2 proteins were measured in 59 paired (grossly normal and cancer) tissues by an enzyme immunoassy method. The cutoff value for gene overexpression was defined as the level of mean expression in normal tissue plus two s.d. A total of 59% of the patients consumed alcohol, 90% smoked tobacco, and 90% chewed betel quid. Of the patients assayed, 34 (58%) and 24 (41%) had EGFR and Her-2 overexpression, with average 3.5- and 1.5-fold elevations. EGFR overexpression has been shown to be statistically associated with T stage, N stage, overall TMN stage, primary tumour depth, lymph node extra-capsular spread, and poor survival. Her-2 overexpression, however, did not demonstrate a similar association with clinicopathological parameters or therapeutic outcome. On multivariant analysis, EGFR overexpression (P=0.041) and N stage (P=0.024) were the only independent factors for overall survival. These results indicate that the molecular targeting therapy to EGFR may be a treatment for oral cavity cancer in the betel quid-chewing prevalent area.

Nonlinear bio-photonic crystal effects revealed with multimodal nonlinear microscopy.

Highly optically active nonlinear bio-photonic crystalline and semicrystalline structures in living cells were studied by a novel multimodal nonlinear microscopy. Numerous biological structures, including stacked membranes and aligned protein structures are highly organized on a nanoscale and have been found to exhibit strong optical activities through second-harmonic generation (SHG) interactions, behaving similarly to man-made nonlinear photonic crystals. The microscopic technology used in this study is based on a combination of different imaging modes including SHG, third-harmonic generation, and multiphoton-induced fluorescence. With no energy release during harmonic generation processes, the nonlinear-photonic-crystal-like SHG activity is useful for investigating the dynamics of structure-function relationships at subcellular levels and is ideal for studying living cells, as minimal or no preparation is required.

Low frequency of HLA-B*2706 in Taiwanese patients with ankylosing spondylitis.

The presence of HLA-B27 in patients affected with ankylosing spondylitis (AS) was well established prior to the advent of DNA typing of various genes within the major histocompatibility complex (MHC) in humans. However, molecular typing of the MHC genes revealed that B27 comprises a motley assortment of alleles, some of which are strongly positively associated with the disease and some of which are negatively associated with the disease. B*2706 was reported to have a negative association with AS in the Thai population and in Chinese Singaporeans. We report here our finding of an absence of B*2706 in 184 Taiwanese AS patients.

In vitro/in vivo correlations between transdermal delivery of 5-aminolaevulinic acid and cutaneous protoporphyrin IX accumulation and effect of formulation.

BACKGROUND: Photodynamic therapy (PDT) using topical application of 5-aminolaevulinic acid (ALA) has been widely reported for the treatment of a variety of neoplastic and non-neoplastic cutaneous diseases. Although different formulations containing variable amounts of ALA have been applied in PDT, the dose-response relationships between transdermal ALA delivery and cutaneous protoporphyrin IX (PpIX) accumulation have not been studied. OBJECTIVES AND METHODS: The objectives of this study were to investigate the effect of permeability barrier function, ALA concentration and formulation on the in vitro penetration of ALA through nude mouse skin and cutaneous PpIX formation at 2 h following a 2-h application of ALA to nude mouse skin in vivo, and to delineate the relationships in between. RESULTS: Results demonstrated that variations in barrier integrity, in addition to ALA concentration, profoundly influenced ALA delivery to generate PpIX. Saturable correlations were found to exist between PpIX concentrations in both the epidermis and dermis in vivo and its transdermal flux in vitro, and the relationships were well described by the Emax model. The established correlations based on pure aqueous solutions were applicable to different formulations containing hydroxypropylmethylcellulose as the gelling agent and ethylenediamine tetraacetic acid as the iron chelator. Moreover, incorporation of desferrioxamine, another iron chelator, in the formulation prolonged cutaneous PpIX accumulation in the skin in comparison with 3% ALA aqueous solution, but the peak PpIX levels were not increased. Application of a liposomal formulation resulted in similar prolongation in ALA-induced PpIX accumulation, as well as better epidermal targeting. CONCLUSIONS: Knowledge of the dose-response relationships and the effect of formulation is important for designing optimal formulations and treatment schedules for topical ALA-PDT.

Occupational exposure to wood, formaldehyde, and solvents and risk of nasopharyngeal carcinoma.

Our objective was to evaluate the link between occupational exposures to wood dust, formaldehyde, and solvents and the development of nasopharyngeal carcinoma (NPC). A case-control study was conducted among 375 newly diagnosed cases of NPC in Taipei, Taiwan, and 325 community controls matched to cases on sex, age, and geographical residence (99 and 87% response rates, respectively). Most cases (>90%) were diagnosed with WHO Types 2 or 3 (nonkeratinizing and undifferentiated carcinomas), whereas the remaining cases were diagnosed with WHO Type 1 (squamous cell carcinomas). A complete occupational history was obtained via a personal interview and blindly assessed by an industrial hygienist for intensity and probability of exposure to wood dust, formaldehyde, and solvents. Information on socio-demographic characteristics, cigarette smoking, dietary consumption of nitrosamines, and other potential confounding factors was obtained via a personal interview. Blood specimens were tested for human leukocyte antigen class I/II genotypes, polymorphisms in cytochrome P450 2E1 genotype, and various anti-EBV antibodies known to be associated with NPC. Analysis was performed using logistic regression; relative risk (RR) estimates and 95% confidence intervals (CI) were calculated. Individuals exposed to wood dust had an adjusted RR of 1.7 (95% CI = 1.0-3.0). Those exposed to wood dust for >10 years had an adjusted RR of 2.4 (95% CI = 1.1-5.0; p(trend) = 0.02). Risk was strongest for those first exposed before the age of 25 years and those seropositive to EBV. Individuals exposed to formaldehyde were at a more modest and nonsignificant increased risk of NPC (RR = 1.4; 95% CI = 0.93-2.2). Those exposed to formaldehyde for >10 years had an adjusted RR of 1.6 (95% CI = 0.91-2.9). The association between formaldehyde and NPC was stronger in analyses restricted to EBV seropositive individuals (RR = 2.7; 95% CI = 1.2-5.9). However, no dose response was observed with increasing duration or cumulative use. No association was observed between solvent exposure and NPC (RR = 1.2; 95% CI = 0.86-1.7). Occupational exposure to wood dust is likely to be involved in the development of NPC, a finding that is consistent with the known link between wood exposure and nasal adenocarcinomas. Formaldehyde exposure is less clearly linked to NPC, whereas exposure to solvents is unlikely to be involved in NPC pathogenesis.

Characteristics of mutations in the p53 gene in oral squamous cell carcinoma associated with betel quid chewing and cigarette smoking in Taiwanese.

p53 mutations are etiologically associated with the development of oral squamous cell carcinomas (OSCCs) or are associated with exposure to specific carcinogens. In this study, we used PCR-single strand conformation polymorphism and DNA sequencing to analyze the conserved regions of the p53 gene (exons 5-9) in OSCC tumor specimens from 187 patients with varied histories of betel quid, tobacco and alcohol use. Ninety-one of the 187 OSCCs (48.66%) showed p53 gene mutations at exons 5-9. The incidence of p53 mutations was not associated with age, sex, TNM stage, status of cigarette smoking or betel quid chewing. However, alcohol drinkers exhibited a significantly higher incidence (57/101, 56.44%) of p53 mutations than non-users (39.53%, 34/86) (P = 0.02). The effect of alcohol on the incidence of p53 mutations was still statistically significant (RR = 2.24; 95% CI, 1.21-4.15) after adjustment for cigarette smoking and betel quid (BQ) chewing. G:C to A:T transitions were the predominant mutations observed and associated with BQ and tobacco use. Alcohol drinking could enhance these transitions. After adjustment for cigarette smoking and BQ chewing, alcohol drinking still showed an independent effect on G:C to A:T transitions (RR = 2.41; 95% CI, 1.01-5.74). These findings strongly suggest an important contributive role of tobacco carcinogens to p53 mutation in this series of Taiwanese OSCCs and alcohol might enhance these mutagenic effects. As safrole-DNA adducts have been detected in 77% (23/30) of the OSCC tissues from Taiwanese oral cancer patients with a BQ chewing history, we cannot rule out the possibility that safrole or other carcinogens present in the BQ may cause a similar pattern of mutagenesis. Determination of the role of safrole and other carcinogens present in BQ on the pattern of p53 gene mutation in OSCC will require further study.

Transpedicular wedge osteotomy for correction of thoracolumbar kyphosis in ankylosing spondylitis: experience with 78 patients.

STUDY DESIGN: This is a retrospective study of surgical correction of thoracolumbar kyphosis caused by ankylosing spondylitis. OBJECTIVE: To report the surgical results of thoracolumbar kyphosis deformity corrected with transpedicular wedge osteotomy performed by a single surgeon at a university hospital. SUMMARY OF BACKGROUND DATA: There has not been a large series in the literature reporting on results of the Thomasen-type closing wedge osteotomy for correction of kyphosis deformity secondary to ankylosing spondylitis, nor has two-level osteotomy of this type in one patient ever been described. METHODS: From 1991 through 1998, 92 transpedicular wedge osteotomies were performed in 78 patients with ankylosing spondylitis for correction of fixed flexion deformity of the thoracolumbar spine. RESULTS: The mean amount of correction for each level of osteotomy was 34.5 degrees (range, 15 degrees -60 degrees ). The largest amount of overall correction for a single patient was 100 degrees. Most of the osteotomies (64 of 92) were done at L2 and L3. Fourteen patients with severe deformity required staged two-level osteotomy. Excellent and good results were obtained in 77 patients (98.7%) at the final follow-up. There was no mortality, nor were there any major neurological complications. CONCLUSIONS: Transpedicular wedge osteotomy can effectively and safely correct kyphotic deformity of the thoracolumbar spine caused by ankylosing spondylitis, regardless of rigidity of the spinal curves. Two-level osteotomy can provide sufficient correction for severe cases.