Risk of tuberculosis comparison in new users of antitumour necrosis factor-α and with existing disease-modifying antirheumatic drug therapy.

WHAT IS KNOWN AND OBJECTIVE: Patients with rheumatic disease are at risk for infections. Evaluating antitumour necrosis factor (anti-TNF) drug-associated risk of infections requires justification of baseline risk in the population at high risk of infection. We examined the incidence of active tuberculosis (TB) and its risk factors in patients with rheumatic disease started with anti-TNF-α therapy or with existing disease-modifying antirheumatic drug (DMARD) therapy. METHODS: A retrospective cohort study of anti-TNF-α therapy new users (anti-TNF-α group) and those starting with a DMARD after the failure of at least one other DMARD or who had added to existing DMARD treatment (DMARD group) for rheumatic disease in the largest medical setting in Taiwan from 1 January 2005 through 31 November 2013 was conducted to determine relative risk of TB between patient groups. Patients in the DMARD group were stratified into "mild" and "severe" disease severity as proxies for low and high background risk of infection. RESULTS AND DISCUSSION: A total of 3640 patients were enrolled (anti-TNF: 955; DMARD: 2685). The incidence of TB was 903.9/100 000 patient-years for anti-TNF-α new users and 391.7/100 000 patient-years for DMARD switchers. In Cox regression model, adjusted HR for TB in the anti-TNF-α group was higher than for the entire DMARD group (aHR, 2.41; 95% confidence interval [CI], 1.2-4.85), subgroup with mild disease (2.91; 1.31-6.47) and subgroup with severe disease (1.65; 0.68-4.03). Significant independent risk factors for TB were being male, age ≥60 years, history of respiratory disease, glucocorticoids dose >7.5 mg/d and living in a TB-prevalent region. WHAT IS NEW AND CONCLUSION: Anti-TNF-α therapy was independently associated with increased risk of TB in patients with mild disease, but it was not significantly correlated in patients with severe disease after adjusting for confounders.

A retrospective analysis of the factors associated with hypercalcaemia in patients with advanced cancer.

Hypercalcaemia, a common complication of advanced cancer, causes multiple clinical symptoms, deteriorates patients' quality of life, and is associated with poor prognoses. This study aimed to identify the factors that may be associated with hypercalcaemia in advanced cancer by retrospectively reviewing the medical records of patients (n = 404) admitted to the palliative ward of the Kaohsiung Medical University Hospital, Taiwan, from 2006 to 2008. Patients' demographics, clinical data and symptoms were recorded. Seventy-nine of 404 patients had hypercalcaemia (19.6%), predominant in cases of head-and-neck cancer and haematological malignancies (P < 0.05), but not in those of bone metastases. Hypercalcaemia was associated with consciousness disturbances and leucocytosis (P < 0.05). We recommend that ionised (corrected) calcium levels be monitored clinically in patients with advanced cancer especially when consciousness disturbances are noted, or when head-and-neck or haematological malignancies are present. Testing of free calcium levels is also recommended in patients with leucocytosis.

Possible association of nicotinic acetylcholine receptor gene (CHRNA4 and CHRNB2) polymorphisms with nicotine dependence in Japanese males: an exploratory study.

INTRODUCTION: Smoking is a leading global cause of avoidable mortality. It has been reported that the nicotinic acetylcholine receptor (CHRNA4 and CHRNB2) genes might be associated with smoking behavior in several ethnic populations. However, no study between the 2 genes and nicotine dependence (ND) using a Japanese population has been reported. METHODS: We examined the association between ND and 5 single nucleotide polymorphisms (SNPs) within the CHRNA4 and 3 SNPs within the CHRNB2 using a well characterized sample of 558 Japanese healthy male workers with a relatively homogeneous background. The Fagerström test for nicotine dependence (FTND) was used to quantify the degree of ND. Additionally, we explored the effect of gene-gene interactions of the 2 genes on ND. RESULTS: We found CHRNB2 rs4845652 genotypes to be associated with FTND scores under an additive genetic model: rs4845652 T-allele carriers had lower ND levels (p=0.038; when adjusted for smoking duration: p=0.052). Furthermore, we demonstrated a possible gene-gene interaction of CHRNA4 and CHRNB2 on ND in a dose-dependent manner: those smokers with CHRNA4 rs1044397 GG or GA genotypes along with CHRNB2 rs4845652 CC genotype are likely to demonstrate higher ND scores. DISCUSSION: These findings suggest that CHRNB2 rs4845652 T-allele carriers may be associated with lower levels of ND, and that certain allelic combinations of CHRNA4 and CHRNB2 might be correlated with higher ND levels. This preliminary study has certain limitations (issues such as sample size/power and multiple testing) that need to be taken into account, and the present work thus has an experimental nature.

Targeted therapy with fatty acid synthase inhibitors in a human prostate carcinoma LNCaP/tk-luc-bearing animal model.

BACKGROUND: Fatty acid synthase (FASN) is highly upregulated in human prostate carcinomas. Inhibition of FASN could arrest cell cycle and trigger apoptosis rapidly, implying the reliance of cancer cell survival on FASN. However, little is known about the effect of C75, a FASN inhibitor, and siFASN (that is, small interfering RNA targeted at FASN) on prostate cancer in living subjects. METHODS: We used C75 and siFASN to mediate the endogenous fatty acid metabolism in LNCaP human prostate cancer cells stably expressing herpes simplex virus type 1 thymidine kinase (HSV1-tk) and luciferase (luc) reporter genes, and assessed the effect of FASN blockade with different schedules of administration on tumor growth using noninvasive molecular imaging. RESULTS: FASN blockade exhibited the proliferative inhibition and induced G1-phase cell cycle arrest of LNCaP cells. For in vivo studies, the tumor growth inhibition by C75 (total 120 mgkg(-1); 30 mgkg(-1) once a week or 15 mgkg(-1) twice a week for 4 weeks) and siFASN (1.4 mgkg(-1) every alternate day up to 16 days) treatments were 80% and 70%, respectively, compared with that of the control. CONCLUSION: The results suggest that C75 may be superior to siFASN in anticancer effect on prostate cancer.

Lifetime exposure to cigarette smoking and the development of adult-onset atopic dermatitis.

BACKGROUND: Adult-onset atopic dermatitis (AD) has recently been recognized as a distinct disease entity, but its risk factors have not yet been clearly defined. Although gestational and perinatal exposure to tobacco smoking may be associated with the development of classic AD, the association between active/passive smoking and adult-onset AD remains controversial. OBJECTIVES: To determine if exposure to smoking, including environmental tobacco smoke (ETS), is associated with the risk of adult-onset AD. METHODS: Tobacco smoking and exposure to ETS were measured in a case-control association analysis in 83 patients with physician-diagnosed adult-onset AD and 142 age- and sex-matched controls. RESULTS: Multiple logistic regression analyses showed that, among the potential environmental risk factors, both current and ever smoking were significant risk factors for adult-onset AD [odds ratio (OR) 4·994 and 3·619, respectively], compared with never smoking. Also, packs per year was significantly associated with adult-onset AD (OR 1·058, 95% confidence interval 1·028-1·089), suggesting a lifelong cumulative risk in current smokers. Moreover, nonsmokers with adult-onset AD reported significantly more exposure to ETS. CONCLUSIONS: Early and/or current exposure to cigarette smoking may contribute cumulatively to the development of adult-onset AD. Exposure to ETS in childhood is associated with the development of adult-onset AD. Adults should be discouraged from smoking to prevent adult-onset AD in themselves and their family members.

Mechanical injuries to the ipsilateral non-diseased lobes(s) during pulmonary resection--another factor causing postoperative complications.

BACKGROUND: The occurrence of complications after major pulmonary resection is known to be related to various factors. However, peri-surgical injuries to the ipsilateral non-diseased lobes(s) occurring during resection have never been mentioned in the literature. This study aimed to verify the injury in cases after lobectomy and wedge resection. METHODS: Data from eighteen patients who underwent lobectomy or wedge resection for malignant tumor between January 2003 and January 2004 were collected. All patients had pre- and postoperative examinations of alveolar-capillary membrane (A/C) permeability using 99m TC-DPTA radioaerosol. RESULTS: Ten lobectomies and eight wedge resection were performed. Using the paired t-test with each patient's pre-operative A/C permeability as his own control data, the postoperative A/C permeability of the ipsilateral non-diseased lobe(s) was found to be significantly increased. The degree of increase in the lobectomy group was the same as that in the wedge resection group. However, no significant change was found on the contralateral side in both groups. CONCLUSION: The degree of increase of permeability was the same in both groups, indicating that the effects of stretch on the surviving lung are not a contributing factor to the change in A/C permeability. The mechanical injuries during the pulmonary surgical procedure alter the permeability, which could be a possible factor causing postoperative pulmonary complications.

Once-daily vs. twice-daily intrapleural urokinase treatment of complicated parapneumonic effusion in paediatric patients: A randomised, prospective study.

To evaluate the effective dose frequency (once daily vs. twice daily) of intrapleural urokinase treatment in children who required tube thoracostomy for drainage of a complicated parapneumonic effusion, we designed a randomised prospective study in a tertiary medical centre in Taiwan. From June 2002 to January 2005, 30 paediatric patients with complicated parapneumonic effusion who had received chest tube drainage were randomised 1 : 1 to the once-daily (urokinase 5000-6000 IU/kg/dose) or twice-daily (urokinase 2500-3000 IU/kg/dose) treatment. We compared clinical manifestations and outcomes in both groups. There were no differences in pleural effusion characteristics between the groups. Six patients had Streptococcus pneumoniae, one had Staphylococcus aureus, one had Group A Streptococcus, and 22 had unknown pathogens. There were no significant differences between the once- vs. twice-daily group in the amount of drained pleural fluid (564.9 +/- 422.1 ml vs. 560.5 +/- 198.6 ml, respectively), fever duration after chest tube insertion (4.3 +/- 3.2 days vs. 5.3 +/- 2.7 days), or total admission days (14.3 +/- 3.9 days vs. 14.6 +/- 3.0 days) (p > 0.05 for all). Only two patients (one in each group) required the surgery. Thus, we found that both once- and twice-daily administration of urokinase were similarly efficacious, and resulted in good clinical outcomes. Both obviated the need for surgery in most (93%) cases of pneumonia with complicated parapneumonic effusion in this series. A larger, multicentre study is necessary to verify our findings.

Comparison of radiographic landmarks and the echocardiographic SVC/RA junction in the positioning of long-term central venous catheters.

BACKGROUND: When implanting a permanent central venous catheter, the usual aim is to place the tip at the superior vena cava/right atrial (SVC/RA) junction. However, data validating radiographic landmarks of the SVC/RA junction are limited. This investigation was undertaken to compare the radiographic landmarks with the SVC/RA junction as determined by transesophageal echocardiography (TEE). METHODS: In 20 adult oncologic patients undergoing implantation of a permanent subcutaneous central venous catheter, the catheter tip was placed in the SVC/RA junction under TEE guidance. The position of the catheter tip on chest X-ray, which represented the echocardiographic SVC/RA junction, was then compared with a standard radiographic landmark of the SVC/RA junction and with thoracic vertebral levels. RESULTS: In all but two patients radiographic SVC/RA junctions were identified. The echocardiographic SVC/RA junction ranged from 0.6 cm above to 2.8 cm below the radiographic SVC/RA junction. There was a significant difference between the distance from the carina to the radiographic SVC/RA junction and the distance from the carina to the echocardiographic SVC/RA junction. The thoracic vertebral body correlating with the echocardiographic SVC/RA junction ranged from the sixth to the ninth level. CONCLUSION: Both the radiographic SVC/RA junction and the thoracic vertebral bodies are not reliable landmarks for the SVC/RA junction defined by TEE. Physicians should be aware that using the radiographic SVC/RA junction to confirm proper positioning of permanent central venous catheters risks placing the catheter tip in the upper SVC, with subsequent potential long-term complications. More reliable radiographic landmarks for the SVC/RA junction should be investigated.

Transepidermal water loss, serum IgE and beta-endorphin as important and independent biological markers for development of itch intensity in atopic dermatitis.

BACKGROUND: Although itch is the predominant symptom of atopic dermatitis (AD), it is poorly characterized and subjective. The objective assessment of itch intensity is important for treatment and follow-up in patients with AD. OBJECTIVES: To determine what objective clinical parameter(s) could be used as biomarker(s) for itch intensity in patients with AD. METHODS: This is a retrospective and cross-sectional study. Seventy-five patients, aged 7 months-49 years with equal sex ratio, were enrolled in 2000 according to criteria proposed by Hanifin and Rajka. Thirty-five age- and sex-matched subjects who visited the dermatological clinic but were otherwise healthy served as controls. Subjective itch intensity was divided into four grades of severity. Disease severity was measured by SCORAD index, which also includes itch intensity as part of the measurement. Transepidermal water loss (TEWL) and skin surface pH were measured by noninvasive methods in clinically normal skin on the forearm. Serum beta-endorphin and vasoactive intestinal peptide (VIP) were determined by radioimmunoassay. Ordinal logistic regression was used to assess the trend of the subjective itch intensity and SCORAD index by serum IgE, beta-endorphin, VIP, TEWL and skin pH. RESULTS: There were significant trends for itch intensity with IgE, beta-endorphin and TEWL. After adjustment for sex, age and other variables, the odds ratio (OR) for itch intensity by log IgE, beta-endorphin and TEWL was 2.103 [95% confidence interval (CI) 1.222-3.618], 1.100 (95% CI 1.005-1.203) and 1.081 (95% CI 1.009-1.158), respectively. The OR for disease severity by log IgE, beta-endorphin and TEWL was 2.250 (95% CI 1.149-4.407), 1.156 (95% CI 1.086-1.231) and 1.071 (95% CI 0.971-1.182), respectively. In contrast, there was no association between serum VIP concentration and itch intensity. CONCLUSIONS: Beta-endorphin and IgE are both useful biomarkers for itch and disease severity in patients with AD, while TEWL is a good biomarker for itch intensity. These biomarkers provide a way to assess the itch intensity in patients with AD.

Bilateral video-assisted thoracoscopic thymectomy vs. extended transsternal thymectomy in myasthenia gravis: a prospective study.

The optimal approach to thymectomy remains controversial. This study is designed to prospectively compare the results between bilateral video-assisted thoracoscopic thymectomy (BVTx) and extended transsternal thymectomy (ETTx) in patients with myasthenia gravis (MG) without thymoma. Fifteen patients who had undergone BVTx and 16 patients who had undergone ETTx were compared for age, gender, severity of disease, preoperative duration of disease, operative time, intraoperative blood loss, postoperative complications, hospital stay, duration of chest tube drainage, thymic histopathology, pain perception by visual analog scale (VAS), remission and improvement rate, period of follow-up, and activities of daily living (ADL). Fisher's exact test, t test and paired t test were used for statistical analysis. BVTx had longer operative time and less intraoperative blood loss than that of the ETTx. Their remission rates and their degree of postoperative ADL improvement were not significantly different. However, the lowering of VAS was significantly greater in the sternotomy group at 3 months. All other parameters were not significantly different. No mortality was noted in the series. We consider BVTx as an effective alternative procedure to the transsternal approach for patients with nonthymomatous MG. As more and more people care about cosmetics, BVTx could become the future trend.

Video-assisted thoracic surgery is minimally invasive, but is it less traumatic?

BACKGROUND: Video-assisted thoracic surgery (VATS) is a minimally invasive procedure. This study aimed to evaluate whether the procedure is less traumatic to the ipsilateral non-diseased lobe(s) than open thoracotomy (OT) during pulmonary resection by a comparison of alveolar-capillary membrane (A/C) permeability. METHODS: Wedge resections were performed in twenty-seven patients with various types of primary and secondary malignant, solitary, pulmonary nodules. Fifteen patients had OT, while 12 patients had VATS. (99 m)Tc-DTPA radioaerosol studies were performed on the day before surgery and on the third or fourth day postoperatively. The images of the ipsilateral non-diseased lobe(s) were compared. RESULTS: Postoperatively, all patients had significantly increased A/C permeability at the ipsilateral non-diseased lobe(s). However, the degree of increase in the VATS group was the same as that of the OT group. Postoperative A/C permeability of the contralateral lung was not significantly different. CONCLUSIONS: Both procedures caused injury to the ipsilateral non-diseased lobe(s) in terms of A/C permeability at the same degree. Although VATS has been considered as a minimally invasive procedure, the trauma caused by VATS to the "disease-free lung" is the same as that caused by open thoracotomy.

Fiber-optic bronchoscopic classification of inhalation injury: prediction of acute lung injury.

BACKGROUND: Fiber-optic bronchoscopy is widely used for the early diagnosis of inhalation injury. However, there is no current bronchoscopic classification of inhalation injury for the prediction of acute lung injury (ALI). Our goal was to devise such a classification. METHODS: Between February 1993 and January 2002, 167 patients with highly suspicious inhalation injuries were collected. All patients received fiber-optic bronchoscopy within 24 h after their accident. In total, 108 patients were diagnosed as positive under direct inspection. The patients were divided into three groups (G(1), G(2), and G(3)) according to the depth of mucosal damage. Six patients were found to be positive by biopsy and were assigned to group Gb. Of these 114 positive cases, 27 developed ALI. Meanwhile, 53 patients were diagnosed as negative; these patients were assigned to group G(0). RESULTS: After analysis, the following results were noted: G(0) (n = 53), two ALI (3.8%); G(1) (n = 49), two ALI (4%); G(2) (n = 46), 15 ALI (33%); G(3)(n = 13),10 ALI (77%); Gb (n = 6), no ALI. We discovered that the deeper the mucosal injuries, the higher the rate of ALI. There were no deaths related to the procedure. CONCLUSIONS: Fiber-optic bronchoscopy is a safe and effective method for the early diagnosis of inhalation injuries. Also, it is a good predictor of ALL. We hope that in the near future, this classification will serve as a treatment guideline for the early prevention of ALI. The more severe the damage, the more alert clinicians need to be to improve the patient's chances for survival.

Relationship of blood lead levels to personal hygiene habits in lead battery workers: Taiwan, 1991-1997.

BACKGROUND: The blood lead concentrations of workers in lead battery factories are more than 4 times higher than those of the general population in Taiwan. Therefore, efforts are needed to reduce lead exposure in this high-risk population. A health promotion program on personal habits that reduce lead exposure has been carried out in a lead battery factory since 1991. This study investigated the longitudinal relationship of workers' blood lead concentrations and personal hygiene habits from 1991 through 1997. METHODS: In each of the 7 years of the study, occupational physicians questioned workers regarding nine personal hygiene items, personal information, and medical history before their annual health examination. The relationship between blood lead concentrations and personal hygiene habits was analyzed by longitudinal multiple regression in a mixed effect model with adjustment for potential confounders. In addition, the risk ratio of a blood lead concentration exceeding 40 micrograms/dL in men and 30 micrograms/dL in women (the action levels set by the Department of Health, Taiwan) was estimated by generalized estimating equations. RESULTS: Blood lead levels decreased significantly in the first 5 years of the study. The personal habits most closely related to blood lead concentrations were smoking at work sites (estimated coefficient = 3.13, P < 0.001), and eating at work sites (estimated coefficient = 1.38, P = 0.069). The risk ratio for workers with both these habits exceeding the action level of blood lead was 2.93 (95% CI 1.27-6.77). Difference in job titles, however, accounted for a major portion of the variance in blood lead. For example, working in "pasting" and "plate-cutting" was associated with blood lead elevations > 20 micrograms/dL in comparison to the "low- or no-exposure jobs." CONCLUSIONS: Health promotion programs can decrease exposure of lead workers; reducing the practices of smoking and eating at work sites should be the core of such programs. However, a major reduction in lead exposure for some jobs (e.g., "pasting" and "plate cutting") in lead battery factories in Taiwan is unlikely to occur without major engineering changes.

Effects of heparin on platelet aggregation and release and thromboxane A2 production.

Heparin, when added to citrated platelet-rich plasma (PRP), caused potentiation of platelet aggregation and the release reaction induced by the aggregating agents adenosine diphosphate (ADP), arachidonic acid, collagen, and epinephrine. At low concentrations (4.7 x 10(-5) M) arachidonic acid failed to cause aggregation of platelets in citrated PRP. However, in the presence of heparin, the same concentration of arachidonic acid caused aggregation. Examination of PRP for the presence of thromboxane A2 (TxA2) by use of a bioassay revealed that heparin also stimulated release of TxA2. This finding indicated that platelets released more TxA2 when they were challenged by low concentrations of arachidonic acid in the presence of heparin than in its absence. Platelets were labeled with 3H-arachidonic acid and 14C-serotonin, and attempts were made to determine whether heparin stimulated the platelet release reaction first with subsequent increased production of TxA2, or alternatively, whether heparin stimulated TxA2 production first with subsequent enhancement of the release reaction. In view of the demonstrated simultaneous release of 14C-serotonin and 3H-arachidonic acid metabolites, it appeared that either release of 14C and 3H occurs concurrently or, even if one of these events is dependent on the other, both events take place in rapid succession. Timed sequential studies revealed that in the presence of arachidonic acid, the addition of heparin hastened the apparently simultaneous release of both 14C and 3H.