[Efficacy of selective bronchial occlusion in the treatment of intractable pneumothorax].

Objective: To analyze the effect of selective bronchial occlusion (SBO) in the treatment of intractable pneumothorax. Methods: A total of 86 patients with refractory pneumothorax treated with SBO in the Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Fujian Medical University from January 1, 2019 to December 31, 2021 were included in this study. The basic information, diagnosis and treatment of the patients were collected and analyzed based on their inpatient records. Results: The age of the subjects was (62±11) years old, and 83 cases (96.5%) were male. The first time SBO cure rate was 30.2% (26/86). The effective rate of the first time SBO treatment was 38.4% (33/86), and the final cure rate of SBO was 59.3% (51/86). The total cure rate of SBO combined with other therapies was 73.3% (63/86). The median time [M (Q1, Q3)] from the first plugging to the complete cessation of air leakage in SBO cured patients was 6.5 (3, 7) days, which was shorter than that in the final extubation patients after SBO [11 (7, 19) days] (H=30.24, P<0.001). The median [M (Q1, Q3)] length of hospital stay of the first SBO cured patients was 19 (14, 25) days, which was shorter than that of all patients [28 (19, 37) days] (H=12.89, P=0.002). The median [M (Q1, Q3)] hospitalization expenses of patients with first SBO cure, effective SBO treatment and ineffective SBO treatment were 23 187 (18 906, 27 798), 41 580 (29 388, 50 762) and 38 462 (27 542, 51 720) yuan, respectively, and the difference was statistically significant (H=18.58, P<0.001). The incidence of complications after SBO was 7.59% (11/145). Conclusion: SBO has good efficacy and relative high safety in the treatment of intractable pneumothorax.

[A comparison of clinical characteristics between patients with and without"recurrence"RNA positive with COVID-19].

Objective: To analysis the clinical characteristics of"recurrence"RNA positive patients with Coronavirus disease 2019 （COVID-19） and compared with those without"recurrence". Methods: 98 patients with COVID-19 in Wuhan Jinyintan Hospital and designated treatment hospitals in Quanzhou were included in this study from February 2020 to April 2020. There were 55 males and 43 females， aged from15 to 83 years， with a median age of 57.5 years， in which 20 cases were complicated with basic diseases. 15 of these patients had been diagnosed and hospitalized had been found as"recurrence"2019-nCoV RNA positive after discharge while the other 83 cases were all negative. The clinical classification of all patients was common type. Clinical data of the COVID-19 RNA"recurrence"patients were collected， and general situations， symptoms， laboratory examinations and CT images were also observed and analyzed. The patients were divided into 2019-nCoV"recurrent"group and 2019-nCoV"non-recurrent"group. There are 10 males and 5 females in 2019-nCoV"recurrent"group while 45 males and 38 females in"non-recurrent"group （χ²=0.800，P=0.371）. The age of 2019-nCoV"recurrent"group （57±21） was higher than that of"non-recurrent"group（53±17）. 8 of 15 the COVID-19"recurrent"group patients and 12 of 83"non-recurrent"patients have basic diseases. IgG and IgM of 2019-nCoV， IL-6， procalcitonin， ESR， CRP， BNP and other serum biochemical index levels were measured and compared between groups. Results: （1） The proportion of patients with common type of COVID-19 was 15.3% during 2-week medical observation after discharge. （2） All of the 2019-nCoV"recurrent"patients were hospitalized due to COVID-19 RNA positive， when they were quarantined after discharged from hospital. All the patients with mild symptoms which were clarified as common type， including 5 cases of fever， 6 cases of cough， 5 cases of expectoration， and 2 cases of slight shortness of breath. The time of symptoms appeared on （5.73±2.82） days after discharge. （3） The serum procalcitonin of all 2019-nCoV"recurrent"group patients were normal（all<0.05 ng/ml）. The BNP of"recurrent"group （151±171） ng/L， was higher than that of"non-recurrent"group （63±78） ng/L （t = 3.207， P = 0.000）. There was no significant difference in laboratory tests like leukocyte ［（6.17±2.4） and （6.04±2.41）×109/L］， lymphocyte［（1.59±0.52） and （1.32±0.64）×109/L］， CRP ［（12.54±28.20） and （21.74±25.63）mg/L］， ESR ［（31.07±28.72） and （34.10±22.16）mm/1 h］， AST ［（24.73±9.15） and （30.24±23.20）U/L］， ALT ［（22.60±12.82） and （36.47±34.12）U/L）， LDH ［（268±208） and （270±164）U/L］， D-dimer ［（0.60±0.50） and （0.84±0.98）µg/L］， ferritin ［（294±195） and （395±319）µg/L］， IL-6 ［（9.17±6.42） and （14.28±17.74）ng/Lï¼½ and BUN （5.77±2.66） and （4.74±2.81）U/Lï¼½ between"recurrent"and"non-recurrent"groups （all P>0.05）. （4） In"recurrent"group， ground glass， exudative or solid lesions could be found in most of the chest CT performed on re-admission. Meanwhile， fibrosis lesion was relatively rare. （5） There were no secondary transmissions were found to be caused by the 2019-nCoV"recurrent"group patients. Conclusions: Most of the 2019-nCoV patients had underlying diseases and active lesions were still found in CT images， so the possibility of virus replication may still exist. All"recurrent"patients had mild illness which may suggest that they were in recovery stage, and no evidence of transmission is found.

[Relationship between selenium and the risk for oral cancer: a case-control study].

Objective: To explore the relationship between selenium and the risk for oral cancer. Methods: We performed a case-control study in 325 cases of newly diagnosed primary oral cancer from the First Affiliated Hospital of Fujian Medical University and 650 controls from the same hospital and community. Unconditional logistic regression and stratification analyses were used to explore the association between selenium and oral cancer. Adjusted OR and corresponding 95%CI were calculated. The analyses on multiple interactions between selenium and smoking or drinking status, and fruit or fish intake frequencies were conducted. Results: The level of serum selenium was 112.42 (80.98-145.06) µg/L in the case group, which was lower than 164.85 (144.44-188.53) µg/L in control group, the difference was statistical significant (P<0.01). There was a negative correlation between serum selenium level and the risk for oral cancer regardless of smoking and drinking status, and fruits and fish intake frequencies (P<0.05). There were multiple interactions between serum selenium level and smoking or drinking status, and fruit and fish intakes. Conclusions: The high level of serum selenium is a protective factor for the incidence of oral cancer, and serum selenium has multiple interactions with smoking or drinking status, and fruit and fish intakes. Therefore, reducing tobacco use and alcohol consumption and increasing the intakes of fruit and fish can reduce the risk for oral cancer to some extent.

Simulation of postoperative occlusion and direction in autotransplantation of teeth: application of computer-aided design and digital surgical templates.

Autotransplantation of teeth requires optimisation of both occlusion and direction to ensure minimal injury to the dental crown and the alveolar bone. We describe a method that could simulate postoperative occlusion and direction of the donor tooth by using CAD and digital surgical templates, and evaluate the postoperative effect in five patients who had teeth autotransplanted. Computed tomographic data were imported into ProPlan CMF 3.0 software, the donor tooth was simulated to replace the recipient site according to the position of the occlusion and alveolar bone, and a digital template was designed to guide preparation of the socket. A computer-aided, rapid prototyped, tooth was used to match the socket and, finally, an occlusal template was designed to ensure that the donor tooth was in the simulated position. We compared the position of the tooth in the simulation with its postoperative position using ProPlan CMF 3.0 software. In this way it was possible to simulate and guide the donor tooth accurately to the recipient site. At six-month follow up all teeth had survived successfully. Given the efficiency and precision of placement and the success, we conclude that CAD can successfully help to simulate occlusion and direction in autotransplantation of teeth while simplifying the procedure.

[Association of single nucleotide polymorphisms of TBX5 gene and environmental exposure index with susceptibility to oral cancer].

Objective: To explore the association of TBX5 polymorphisms and environmental exposure index with susceptibility to oral cancer. Methods: A case-control study was conducted to collect 300 oral cancer patients hospitalized in the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University from September 2010 to December 2016. A total of 445 non-tumor patients were selected as the control group. Questionnaires were used to collect the information of all subjects and 5 ml peripheral blood was collected to detect single nucleotide polymorphisms (SNPs) of the rs10492336 locus of TBX5 gene. According to the environmental exposure index score, subjects were divided into two groups, low risk group (0-2.31) and high risk group (2.32-11.76). To analyze the association of TBX5 gene rs10492336 SNPs, environmental exposure index and oral cancer and its interactions. Results: The age of all subjects in the case group and control group were (56.19±13.10) years and (54.56±12.48) years old. Compared with CC genotype, the OR (95%CI) values of the co-dominant genetic model AC genotype and the dominant genetic model AC+AA genotype were 0.69 (0.49-0.98) and 0.70 (0.51-0.97), respectively. Compared with the low risk group, the OR (95%CI) risk of oral cancer in the high risk group was 3.72 (2.55-5.43). The results of gene-environment interaction analysis showed that compared with the group with CC genotype and high risk of environmental exposure index, the OR (95%CI) value of oral cancer in the group with AC+AA genotype and low risk of environmental exposure index was 0.18(0.10-0.31). Furthermore there was a multiplicative interaction between rs10492336 SNPs and environmental exposure index (ß=-0.405, P<0.001). Conclusion: This study suggests that the TBX5 gene rs10492336 SNPs and environmental exposure index were associated with oral cancer. And there was a multiplication interaction between rs10492336 SNPs and environmental exposure index.

[A novel prognostic index for oral cancer in Fujian province].

Objective: To explore the survival factors and construct a prognostic index (PI) for oral squamous cell carcinoma (OSCC). Methods: From January 2004 to June 2016, a total of 634 patients with pathologically confirmed OSCC were recruited in a hospital of Fujian. The clinical and follow-up data of all the patients with pathologically confirmed OSCC were collected to identify the factors influencing the prognosis of OSCC. All the patients were randomly divided into two groups: modeling group (modeling dataset, n=318) and validation group (validation dataset, n=316). Randomization was carried out by using computer-generated random numbers. In the modeling dataset, survival rates were calculated using Kaplan-Meier method and compared using the log-rank test. Cox regression model was used to estimate the hazard ratio (HRs) and 95% confidence intervals (CIs) of prognosis factors. An PI for OSCC patients prognostic prediction model was developed based on ß value of each significant variable obtained from the multivariate Cox regression model. Using the tertile analysis, patients were divided into high-risk group, moderate-risk group, and low-risk group according to the PI, the Akaike information criterion (AIC) and Harrell's c-statistic (C index) were used to evaluated the model's predictability. Results: Results from the multivariate Cox regression model indicated that aged ≥55 years (HR=2.22, 95%CI: 1.45-3.39), poor oral hygiene (HR=2.12, 95%CI: 1.27-3.54), first diagnosis of lymph node metastasis (HR=5.78, 95%CI: 3.60-9.27), TNM stage Ⅲ-Ⅳ (stage Ⅰ as reference) (HR=2.43, 95%CI: 1.10-5.37) and poor differentiation (well differentiation as reference) (HR=2.53, 95%CI: 1.60-4.01) were the risk factors influencing the prognosis of OSCC. The PI model had a high predictability in modeling group and validation group (AIC and C index were 1 205.80, 0.700 2 and 1 150.47, 0.737 3). Conclusion: Age, poor oral hygiene, first diagnosis of lymph node metastasis, TNM stage and histological grade were factors associated with the prognosis of OSCC, and the PI model has a certain significance in the clinical treatment of OSCC.

[A case-control study: association between oral hygiene and oral cancer in non-smoking and non-drinking women].

Objective: To evaluate the influence of oral hygiene on risk of oral cancer in non-smoking and non-drinking women. Methods: From September 2010 to February 2016, 242 non-smoking and non-drinking female patients with pathologically confirmed oral cancer were recruited in a hospital of Fuzhou, and another 856 non-smoking and non-drinking healthy women from health examination center in the same hospital were selected as control group. Five oral hygiene related variables including the frequency of teeth brushing, number of teeth lost, poor prosthesis, regular dental visits and recurrent dental ulceration were used to develop oral hygiene index model. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95%CI). The area under the receiver operating characteristic curve (AUROC) was used to evaluate the predictability of the oral hygiene index model. Multivariate logistic regression model was used to analyze the association between oral hygiene index and the incidence of oral cancer. Results: Teeth brushing <2 twice daily, teeth lost ≥5, poor prosthesis, no regular dental visits, recurrent dental ulceration were risk factors for the incidence of oral cancer in non-smoking and non-drinking women, the corresponding OR (95%CI) were 1.50 (1.08-2.09), 1.81 (1.15-2.85), 1.51 (1.03-2.23), 1.73 (1.15-2.59), 7.30 (4.00-13.30), respectively. The AUROC of the oral hygiene index model was 0.705 9, indicating a high predictability. Multivariate logistic regression showed that the oral hygiene index was associated with risk of oral cancer. The higher the score, the higher risk was observed. The corresponding OR (95%CI) of oral hygiene index scores (score 1, score 2, score 3, score 4-5) were 2.51 (0.84-7.53), 4.68 (1.59-13.71), 6.47 (2.18-19.25), 15.29 (5.08-45.99), respectively. Conclusion: Oral hygiene could influence the incidence of oral cancer in non-smoking and non-drinking women, and oral hygiene index has a certain significance in assessing the combined effects of oral hygiene.

[Pickled food, fish, seafood intakes and oral squamous cell carcinoma: a case-control study].

Objective: To investigate the effects between fish, seafood and pickled food intakes on oral squamous cell carcinoma (OSCC). Methods: A case-control study was carried out in Fujian area during September 2010 to December 2016, in which 604 newly diagnosed primary OSCC cases confirmed by pathological diagnosis were collected from hospital and 1 343 control subjects were enrolled from community and healthy hospital population. Demographic data, history of smoking drinking and tea drinking, oral hygiene status and dietary behaviors (fish, seafood and pickled food intakes) were collected by in-person interviews using a standard questionnaire.Using unconditional logistic regression to estimate adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to assess the effects of fish, seafood and pickled food intakes on OSCC. Analysis stratified by smoking, alcohol drinking and bad prosthesis to explore the possible difference in association between subgroups. Multiplicative interactions and additive interactions between fish and bad prosthesis, seafood and alcohol drinking, pickled food and bad prosthesis were assessed by unconditional logistic regression, relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). Results: The average age of case group and control group were separately (58.69±13.92) years old and (59.27±11.37) years old (χ(2)=4.75, P=0.191). The people whose fish and seafood intakes ≥3 times/week had the lower risk of OSCC, the adjusted OR (95%CI) values were 0.63 (0.52-0.77) and 0.51 (0.41-0.64); The stratified analysis indicated that the people having bad prosthesis had the lower risk of OSCC if they eating fish ≥3 times/week, and the adjusted OR (95%CI) values was 0.53 (0.39-0.71); the people having bad prosthesis had the higher risk of OSCC if they eating pickled food ≥3 times/week, the adjusted OR (95%CI) values was 1.37 (1.02-1.88). Regularly eating seafood can decrease the risk of OSCC for non-smokers, smokers, non-drinkers, drinkers, people without bad prosthesis and had bad prosthesis, the adjusted OR (95%CI) values were 0.49 (0.36-0.68), 0.52 (0.37-0.73), 0.41 (0.31-0.55), 0.77 (0.51-0.96), 0.49 (0.36-0.67), 0.59 (0.42-0.83). Crossover analysis showed fish and bad prosthesis exist multiplication interaction relationship (adjusted OR=0.66, 95%CI: 0.44-0.97) and additional interaction relationship (RERI=-0.81, 95%CI:-1.43--0.19; AP=-0.76, 95%CI:-1.35--0.17; S=0.08, 95%CI: 0.01-0.98); pickled food and bad prosthesis exist multiplication interaction relationship (adjusted OR=1.63, 95%CI: 1.06-2.51) and addition interaction relationship (RERI=0.65, 95%CI:0.08-1.22; AP=0.36, 95%CI:0.10-0.62; S=5.19, 95%CI:1.32-54.49). Conclusion: Reducing the consumption of pickled food, quitting smoking and limiting alcohol consumption, and regularly eating fish and seafood can prevent the occurrence of OSCC.

[Re-treatments of recurrence after pelvic floor repair surgery].

Objective: To analyze re-treatments of recurrence after the pelvic floor repair surgery. Methods: The protocol and the effect of re-treatments were investigated by reviewing and analyzing the clinical data of 81 recurrent patients (grade Ⅱ and above), who had received the pelvic floor repair surgery from January 2011 to January 2016. Pelvic organ prolapse quantitation system (POP-Q) and two questionnaires about quality of life [pelvic floor distress inventory-short form 20 (PFDI-20) and pelvic floor impact questionnaire short form (PFIQ-7)] were used to evaluate objective and subjective efficacy, respectively. Results: Among 81 recurrent patients who were followed up for a median of 35 months (10- 69 months), 78 cases (with prolapse up to grade Ⅲ or Ⅳ) were treated by surgical operation with both objective cure rate and subjective satisfaction being 100% (78/78); 3 cases (with grade Ⅱ prolapse) were treated by pelvic floor electrical stimulation biofeedback, and 1 case among the three cases had the vaginal foreign body sensation, the subjective satisfaction was 2/3. The methods of surgical operation for the 78 recurrent patients included: total pelvic floor reconstructive surgery (55 cases; 3 of which involve trachelectomy), anterior pelvic reconstructive surgery (2 cases), posterior pelvic reconstructive surgery (3 cases), Y-mesh sacral colpopexy (2 cases), colpocleisis (11 cases), vaginal hysterectomy combined posterior fornix forming (3 cases), and vaginal hysterectomy combined posterior pelvic reconstructive surgery(2 cases). Conclusion: The extent of recurrence, the recurrent site and complications must be carefully considered and evaluated for re-treatments of recurrence after pelvic floor repair surgery, and then an appropriately individualized re-treatment protocol could be designed for each of the patients.

Tea consumption and its interactions with tobacco smoking and alcohol drinking on oral cancer in southeast China.

BACKGROUND/OBJECTIVES: Epidemiological results on the association between tea consumption and oral cancer remain controversial. We aimed to evaluate the exact relationship between tea consumption and oral cancer in Chinese population. SUBJECTS/METHODS: A large-scale case-control study was conducted on 586 oral cancer patients and 1024 controls frequency-matched by age and gender. Epidemiological data were collected through face-to-face interviews with a structure questionnaire. Unconditional logistic regression model was used to assess the effect of tea consumption on oral cancer stratified by smoking, alcohol drinking and demographics. Quantity of tea consumed (ml/day) was categorized into five subgroups based on quartiles and then its interactions was evaluated with tobacco smoking and alcohol drinking at each subgroup. RESULTS: Tea consumption showed an inverse association with oral cancer for non-smokers or non-alcohol drinkers (the odds ratios (ORs) were 0.610 (95% confidence interval (CI): 0.425-0.876) and 0.686 (95% CI: 0.503-0.934), respectively). For smokers or alcohol drinkers, decreased risk was only observed in those who consumed >800 ml/day. Furthermore, oolong tea consumption was associated with decreased risk of oral cancer in smokers or alcohol drinkers but not in non-smokers or non-alcohol drinkers. Tea consumption combined with smoking or/and alcohol drinking had a greater risk than tea consumption alone, but the risk was roughly reduced from zero to Q4 (>800 ml/day). Additionally, when stratified by demographics, the protective effect of tea was especially evident in females, urban residents, normal body mass index population (18.5-23.9), farmers, office workers and those aged <60 years. CONCLUSIONS: Tea consumption protects against oral cancer in non-smokers or non-alcohol drinkers, but this effect may be obscured in smokers or alcohol drinkers. Additionally, demographics may modify the association between tea consumption and oral cancer.

Influence of oral hygiene and its interaction with standard of education on the risk of oral cancer in women who neither smoked nor drank alcohol: a hospital-based, case-control study.

We know of only limited data about the role of oral hygiene and the risk of oral cancer with different standards of education. The aim of this study was to assess the association between oral hygiene and risk of oral cancer, with stratification by standard of education, in Chinese women. We organised a case-control study with 250 women with oral cancer and 996 age-matched controls in Fujian, China. Data were collected by personal interview using a structured questionnaire. We used unconditional logistic regression with stratification by educational standard to estimate the odds ratios (OR) and 95% CI. Tooth-brushing twice a day or more was inversely related to the risk of oral cancer in women with high school education or above (OR 0.50; 95% CI 0.25 to 0.98), but not in those who were illiterate or had primary-middle school education. Wearing dentures showed an increased risk only in less well-educated women: the OR were 2.23 (95% CI 1.14 to 4.34) for the illiterate and 1.68 (95% CI 1.08 to 2.62) for the primary-middle school group. The loss of more than five teeth and oral ulceration were associated with increased risks of oral cancer in all three groups. There was also a multiplicative interaction between oral hygiene and standard of education for risk of oral cancer (p=0.001). Our results suggest that oral hygiene seems to have a critical role in the risk of oral cancer in Chinese women, but this effect may be modified by their educational standard.

[Tea, coffee intakes and risk of oral squamous cell carcinoma: a case-control study].

Objective: To evaluate the effects of tea and coffee intakes on oral squamous cell carcinoma (OSCC) stratified by milk intake. Methods: A case-control study involving 593 OSCC patients confirmed by pathological diagnoses and 1 128 gender-age frequency matched controls was conducted in Fujian province during September 2010-March 2016. Unconditional logistic regression was used to calculate adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CIs) to assess the effects of coffee, tea intakes and related variables on OSCC. Additive interaction was estimated by relative excess risk interaction (RERI), attributable proportions interaction (API) and synergy index (SI). Results: Tea intake was significantly associated with decreased risk of OSCC: the adjusted ORs were 0.54 for all subjects (95%CI: 0.41-0.71), 0.47 for milk consumers (95%CI: 0.31-0.71) and 0.57 for non-milk consumers (95%CI: 0.40-0.81). Moreover, starting tea drinking at age ≥25 years, moderate tea concentration and water temperature, drinking green tea and oolong tea showed effects to decrease the risk for OSCC in three groups. Additionally, there was a tendency of a reduced risk with increased daily tea drinking and longer tea-drinking period (all trend P<0.05). No significant association was observed between coffee intake and OSCC. A multiplicative but not additive interactions was found between tea drinking and milk intake. Additionally, we did not observe multiplicative and additive interaction between coffee drinking and milk intake. Conclusion: Tea drinking is a protective factor for OSCC, and there is a multiplicative interaction between tea drinking and milk intake. Therefore, tea drinking and increasing intake of milk can reduce the risk of OSCC at certain extent.

Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction.

BACKGROUND: There is increased recognition that cancers of the upper GI tract comprise distinct epidemiological and molecular entities. Erlotinib has shown activity in patients with adenocarcinoma of the oesophagus/gastro-oesophageal junction (GEJ), but not in distal gastric cancer. mFOLFOX6 is one of several active regimens used to treat adenocarcinoma of the Eso/GEJ. This study evaluates the efficacy and safety of mFOLFOX6 and erlotinib in patients with metastatic or advanced Eso/GEJ cancers. METHODS: Patients with previously untreated advanced or metastatic Eso/GEJ adenocarcinoma are treated with oxaliplatin 85 mg m(-2), 5-FU 400 mg m(-2), LV 400 mg m(-2) on day 1, 5-FU 2400 mg m(-2) over 48 h and erlotinib 150 mg PO daily. Treatment was repeated every 14 days. The primary objective was response rate (RR), secondary objectives include toxicity, progression-free survival (PFS), overall survival (OS) and to correlate clinical outcome with expression patterns and molecular alterations in the epidermal growth factor receptor-dependent pathways. RESULTS: A total of 33 patients were treated and evaluable: there were two complete responses, 15 partial responses for an objective RR of 51.5% (95% CI, 34.5-68.6%). Median PFS was 5.5 months (95% CI, 3.1-7.5 months) and median OS was 11.0 months (95% CI, 8.0-17.4 months). The most common grade 3-4 toxicities were: diarrhoea (24%), nausea/vomiting (11%), skin rash (8%) and peripheral neuropathy (8%). The frequency of alterations was KRAS mutations (8%), EGFR mutations (0%) and HER2 amplification (19%). CONCLUSION: In patients with Eso/GEJ adenocarcinoma, mFOLFOX6 and erlotinib is active, has an acceptable toxicity profile and FOLFOX ± erlotinib could be considered for further development.

In vitro and in vivo metabolism of a novel cannabinoid-1 receptor inverse agonist, taranabant, in rats and monkeys.

The metabolism and excretion of taranabant (MK-0364, N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2{[5-(trifluoromethyl)pyridine-2-yl]oxy}propanamide), a potent cannabinoid-1 receptor inverse agonist, were evaluated in rats and rhesus monkeys. Following administration of [¹4C]taranabant, the majority of the radioactivity was excreted within 72 h. In both rats and rhesus monkeys, taranabant was eliminated primarily via oxidative metabolism, followed by excretion of metabolites into bile. Major pathways of metabolism that were common to rats and rhesus monkeys included hydroxylation at the benzylic carbon adjacent to the cyanophenyl ring to form a biologically active circulating metabolite M1, and oxidation of one of the two geminal methyl groups of taranabant or M1 to the corresponding diastereomeric carboxylic acids. Oxidation of the cyanophenyl ring, followed by conjugation with glutathione or glucuronic acid, was a major pathway of metabolism only in the rat and was not detected in the rhesus monkey. Metabolism profiles of taranabant in liver microsomes in vitro were qualitatively similar in rats, rhesus monkeys and humans and included formation of M1 and oxidation of taranabant or M1 to the corresponding carboxylic acids via oxidation of a geminal methyl group. In human liver microsomes, metabolism of taranabant was mediated primarily by CYP3A4.

Feasibility of disinfection kinetics and minimum inhibitory concentration determination on bacterial cultures using flow cytometry.

Disinfection kinetics has been well established for selected antimicrobial agents on isolated bacterial strains. Due to the difficulties of culturing most bacteria, the majority of these studies have been limited to readily cultivable microorganisms of a single type or family. This study explores the feasibility of using flow cytometry for characterising the disinfection kinetics and minimum inhibitory concentration (MIC) of an Escherichia coli culture and a microbial consortium. The proposed method relies on fluorescent dye molecules to indicate the morphological and physiological status of numerous individual cells. Biocides of varying effectiveness and inactivation mechanisms (chlorine, iodine, and silver) were used to evaluate this novel application. Using pseudo-first-order kinetics, the coefficients of specific lethality of chlorine and iodine on Escherichia coli were 4.71 and 3.78 x 10(-3) L mg(-1) min(-1) and MIC of silver ion was between 60 and 80 microg L(-1). The coefficients of specific lethality of chlorine and iodine on the microbial consortium were 4.96 and 8.89 x 10(-3) L mg(-1) min(-1) and MIC of silver ion was between 40 and 60 microg L(-1). This method can be used to provide a rapid and consistent way of determining disinfection kinetics and MICs for pure and mixed bacterial cultures and can potentially be used to examine water and wastewater disinfection efficiency. However, caution should be used to ensure that the physiological and morphological status characterised by cytodyes is a result of the inactivation mechanisms of the disinfectants evaluated.

Prevalence and correlates of HIV testing in a multi-site sample of young men who have sex with men.

This study assessed HIV testing among 2,621 urban young men who have sex with men (YMSM). Of these, 77% were men of colour, 30% reported recent unprotected anal intercourse (UAI), 22% had never tested for HIV and 71% had not tested recently. Ever testing was associated with older age (OR=1.28), being employed (OR=1.34), exposure to more types of HIV preventions (linear trend p=0.02), sex with a main partner (OR=1.92), sex with a non-main partner (OR=1.36), UAI with a non-main partner (OR=0.53), UAI in the last three months (OR=1.32), knowing a comfortable place for testing (OR=5.44) and social support (OR=1.47). Rates of ever testing increased with behavioural risk with main partners; rates were lowest for men reporting high-risk with non-main partners. Recent testing was associated with greater numbers of HIV-prevention exposures (linear trend p = <0.001), sex with a main partner (OR=1.30), knowing a comfortable place for testing (OR=2.31) and social support (OR=1.23). Findings underscore the urgency of promoting testing among YMSM, point to components for the recruitment and retention of young MSM of colour in testing programmes and highlight the need for a theory-based approach to intervention development.

Importance of mechanistic drug metabolism studies in support of drug discovery: A case study with an N -sulfonylated dipeptide VLA-4 antagonist in rats.

N-(1-(3,5-dichlorobenzenesulfonyl)-2S-methyl-azetidine-2-carbonyl)-L-4-(2',6'-dimethoxyphenyl)phenylalanine (1) is a potent antagonist of the very late activating (VLA) antigen-4. During initial screening, 1 exhibited an apparent plasma clearance (CL) of 227 ml min(-1) kg(-1) in Sprague-Dawley rats following an intravenous bolus dose formulated in an aqueous solution containing 40% polyethylene glycol. Such a high CL value led to speculation that the elimination of compound 1 involved extra-hepatic tissues. However, the apparent plasma CL was reduced to 97 ml in(-1) kg(-1) when a 2-min time point was added to sample collections, and further decreased to 48 ml min(-1) kg(-1) after the dose was formulated in rat plasma. The lung extraction of 1 in rats was negligible whereas the hepatic extraction was > or =90%, based on comparison of area under the curve (AUC) values derived from intra-artery, intravenous, and portal vein administration. In rats dosed intravenously with [(14)C]-1, approximately 91% of the radioactivity was recovered in bile over 48 h, with 85% accounted for in the first 4-h samples. The biliary radioactivity profile consisted of approximately 30% intact parent compound, 20% 1-glucuronide, and 50% oxidation products resulting from O-demethylation or hydroxylation reactions. When incubated with rat liver microsomes, oxidative metabolism of 1 was inhibited completely by 1-aminobenzotriazole (ABT), whereas the oxidation and glucuronidation reactions were little affected in the presence of cyclosporin A (CsA). In contrast, the hepatic extraction of 1 in rats was unperturbed in animals pre-dosed with ABT, but was reduced approximately 60% following treatment with CsA. In vitro, 1 was a substrate of the rat organic anion transporter Oatp1b2, and its cellular uptake was inhibited by CsA. In addition, the hepatic extraction of 1 was approximately 30% lower in Eisai hyperbilirubinaemic rats which lack functional multidrug resistant protein-2 (MRP2). Collectively, these data suggest that the clearance of 1 in rats likely is a result of the combined processes of hepatic oxidation, glucuronidation and biliary excretion, all of which are facilitated by active hepatic uptake of parent compound and subsequent active efflux of both unchanged parent and its metabolites into bile. It was concluded, therefore, that multiple mechanisms contribute to the clearance of 1 in rats, and suggest that appropriate pharmacokinetic properties might be difficult to achieve for this class of compounds. This case study demonstrates that an integrated strategy, incorporating both rapid screening and mechanistic investigations, is of particular value in supporting drug discovery efforts and decision-making processes.

Sociodemographic factors associated with participation by HIV-1-positive pregnant women in an intervention to prevent mother-to-child transmission of HIV in Cote d'Ivoire.

Many HIV-1-seropositive women in Africa who are offered antiretroviral prophylaxis to prevent mother-to-child transmission (MTCT) of HIV do not begin interventions. Research on barriers to participation has not addressed the possible effects of women's sociocultural and economic circumstances. We examined these factors at an MTCT prevention programme in Abidjan, Cote d'Ivoire. We interviewed two groups of women after they had received HIV-positive test results and had been invited by the programme staff to return for monthly follow-up visits before beginning short-course zidovudine prophylaxis. Participants (n = 30) completed follow-up visits and prophylaxis. Non-participants (n = 27) refused or discontinued follow-up visits and did not begin zidovudine. Fewer non-participants had been born in Cote d'Ivoire (67% vs. 97%) or were Ivorian nationals (48% vs. 77%); they had lived in the country for less time (21 vs. 26 median years). They were less likely to be French-literate (37% vs. 77%), and more of them reported having had Koranic education only (18% vs. 0). They more often reported miscarriages, stillbirths, or infant deaths (69% vs. 33%), and had partners with low-ranked jobs (63% vs. 30%). Our findings suggest that the non-participants were more marginal socioculturally and economically in Ivorian society than participants. Greater attention to mitigating the effects of broader structural factors on women's participation in interventions may increase the effectiveness of MTCT prevention in Africa.

Low-dose trimetrexate glucuronate and protracted 5-fluorouracil infusion in previously untreated patients with advanced pancreatic cancer.

BACKGROUND: 5-Fluorouracil (5-FU)-based regimens have not been shown to prolong survival or provide clinical benefit in patients with advanced pancreatic cancer. The purpose of this study was to determine the tolerability of protracted venous infusion (PVI) of 5-FU, modulated by a low dose of the synthetic antifolate trimetrexate, in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Twenty-three chemotherapy-naïve patients were evaluated. Patients were enrolled in four consecutive cohorts in which the weekly dose of trimetrexate was escalated in 10 mg/m2 increments, from 20 to 50 mg/m2. PVI 5-FU was administered at a fixed dose of 225 mg/m2/day. Treatment was administered for 6 successive weeks, every 8 weeks. RESULTS: Twenty-two patients were assessable. The maximum tolerated dose of trimetrexate was 40 mg/m2. The most common grade 3 and 4 toxicity was diarrhea. There were no treatment-related deaths. Preliminary analysis of activity revealed a response rate of 9%, with 41% of the patients having stable disease for a median duration of 3.8 months. The median survival for the entire group was 6.9 months (range 1-29 months). A clinical benefit response was experienced by 27.2% of patients. CONCLUSIONS: Low-dose trimetrexate can be safely administered in combination with PVI 5-FU. This treatment is well tolerated and is associated with palliative activity in advanced pancreatic cancer.

Preventive effects of ginsenosides on osteopenia of rats induced by ovariectomy.

AIM: To determine the effect of ginsenosides (GSL) on ovariectomized rats by analysis of cancellous bone histomorphometry. METHODS: Forty Sprague-Dawley female rats at age of 3 months were sham-operated (Sham, n = 8) and treated orally with vehicle, or ovariectomized (OVX, n = 32 which were divided into three group with n = 8 per group) and treated orally with either vehicle, 17alpha-ethynylestradiol (EE, 100 microg . kg-1 . d-1), or ginsenosides (GSL) at 100 or 300 mg . kg-1 . d-1 for 10 weeks. Double in vivo fluorochrome labeling was administrated. The undecalcified longitudinal proximal tibial metaphyseal sections were cut and stained with Goldner's Trichrome (4-micron thickness) or unstained (8-micron thickness) for the bone histomorphometric analysis. RESULTS: After 10 weeks post OVX the cancellous bone mass was lost markedly and showed high bone turnover indices (increased bone resorption and formation). EE decreased the resorptive surface and bone formation rate related to bone turnover and prevented bone loss. GSL at the two doses (100 and 300 mg . kg-1 . d-1) reduced the resorptive surfaces as did EE, but did not depress the mineral bone formation. High dose of GSL greatly increased bone mass and had a tendency to decrease bone turnover when compared with OVX group. CONCLUSION: GSL partially prevented OVX-induced cancellous bone loss by inhibiting osteoclast bone resorption and by a mild depression of bone turnover.