Outcomes of Optimized over Standard Protocol of Rabbit Antithymocyte Globulin for Severe Aplastic Anemia: A Single-Center Experience

Background

Previous reports showed that outcome of rabbit antithymocyte globulin (rATG) was not satisfactory as the first-line therapy for severe aplastic anemia (SAA). We explored a modifying schedule of administration of rATG.

Design and Methods

Outcomes of a cohort of 175 SAA patients, including 51 patients administered with standard protocol (3.55 mg/kg/d for 5 days) and 124 cases with optimized protocol (1.97 mg/kg/d for 9 days) of rATG plus cyclosporine (CSA), were analyzed retrospectively.

Results

Of all 175 patients, response rates at 3 and 6 months were 36.6% and 56.0%, respectively. 51 cases received standard protocol had poor responses at 3 (25.5%) and 6 months (41.2%). However, 124 patients received optimized protocol had better responses at 3 (41.1%, P = 0.14) and 6 (62.1%, P = 0.01). Higher incidences of infection (57.1% versus 37.9%, P = 0.02) and early mortality (17.9% versus 0.8%, P<0.001) occurred in patients received standard protocol compared with optimized protocol. The 5-year overall survival in favor of the optimized over standard rATG protocol (76.0% versus. 50.3%, P<0.001) was observed. By multivariate analysis, optimized protocol (RR = 2.21, P = 0.04), response at 3 months (RR = 10.31, P = 0.03) and shorter interval (<23 days) between diagnosis and initial dose of rATG (RR = 5.35, P = 0.002) were independent favorable predictors of overall survival.

Conclusions

Optimized instead of standard rATG protocol in combination with CSA remained efficacious as a first-line immunosuppressive regimen for SAA.     

Bone mass and quality in patients with juvenile idiopathic arthritis: longitudinal evaluation of bone-mass determinants by using dual-energy x-ray absorptiometry,peripheral quantitative computed tomography,and quantitative ultrasonography

Introduction

Our objective was to evaluate longitudinally the main bone-mass and quality predictors in young juvenile idiopathic arthritis (JIA) patients by using lumbar spine dual-energy X-ray absorptiometry (DXA) scan, radius peripheral quantitative computed tomography (pQCT), and phalangeal quantitative ultrasonography (QUS) at the same time.

Methods

In total, 245 patients (172 females, 73 males; median age, 15.6 years: 148 oligoarticular, 55 polyarticular, 20 systemic, and 22 enthesitis-related-arthritis (ERA) onset) entered the study. Of these, 166 patients were evaluated longitudinally. Data were compared with two age- and sex-matched control groups.

Results

In comparison with controls, JIA patients, but not with ERA, had a reduced spine bone-mineral apparent density (BMAD) standard deviation score (P < 0.001) and musculoskeletal deficits, with significantly lower levels of trabecular bone mineral density (TrabBMD) (P < 0.0001), muscle cross-sectional area (CSA) (P < 0.005), and density-weighted polar section modulus (SSIp) (P < 0.05). In contrast, JIA showed fat CSA significantly higher than controls (P < 0.0001). Finally, JIA patients had a significant reduced amplitude-dependent speed of sound (AD-SoS) (P < 0.001), and QUS z score (P < 0.005).Longitudinally, we did not find any difference in all JIA patients in comparison with baseline, except for the SSIp value that normalized. Analyzing the treatments, a significant negative correlation among spine BMAD values, TrabBMD, AD-SoS, and systemic and/or intraarticular corticosteroids, and a positive correlation among TNF-α-blocking agents and spine BMAD, TrabBMD, and AD-SoS were observed.

Conclusions

JIA patients have a low bone mass that, after a first increase due to the therapy, does not reach the normal condition over time. The pronounced bone deficits in JIA are greater than would be expected because of reduction in muscle cross-sectional area. Thus, bone alterations in JIA likely represent a mixed defect of bone accrual and lower muscle forces.     

Radiation-Induced Temporal Lobe Injury for Nasopharyngeal Carcinoma: A Comparison of Intensity-Modulated Radiotherapy and Conventional Two-Dimensional Radiotherapy

Background

To compare the radiation-induced temporal lobe injury (TLI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) or two-dimensional conventional radiotherapy (2D-CRT).

Patients and Methods

1276 cases of NPC treated with IMRT or 2D-CRT were retrospectively reviewed. A diagnosis of TLI was made on follow-up magnetic resonance imaging (MRI).

Results

The crude incidence of TLI was 7.5% and 10.8% (P = 0.048), and the actuarial 5-year incidence was 16% and 34.9% (P<0.001) for the IMRT and 2D-CRT groups, respectively. Multivariate analysis revealed both T stage (P<0.001) and radiation technique (P<0.001) as independent predictors. Patients with T1, T2 and T3 disease had a significantly higher risk when treated with 2D-CRT (P = 0.005, 0.016, <0.001, respectively). This trend was not evident for T4 patients (P = 0.680). The 2D-CRT group had a longer latency for the development of TLI (P<0.001). Those with T4 disease had a shorter median time to TLI (P = 0.006, 0.042, <0.001 when compared with T1, T2 and T3, respectively).

Conclusions

IMRT is superior to 2DRT for the management of T1-T3 NPC in terms of sparing the temporal lobe. The high incidence of TLI in T4 disease needs to be addressed.     

Comparison of Arterial Spin Labeling and Dynamic Susceptibility Contrast Perfusion MRI in Patients with Acute Stroke

Background

The aim of this study was to evaluate whether arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) can reliably quantify perfusion deficit as compared to dynamic susceptibility contrast (DSC) perfusion MRI.

Methods

Thirty-nine patients with acute ischemic stroke in the anterior circulation territory were recruited. All underwent ASL and DSC MRI perfusion scans within 30 hours after stroke onset and 31 patients underwent follow-up MRI scans. ASL cerebral blood flow (CBF) and DSC time to maximum (T_max) maps were used to calculate the perfusion defects. The ASL CBF lesion volume was compared to the DSC T_max lesion volume by Pearson''s correlation coefficient and likewise the ASL CBF and DSC T_max lesion volumes were compared to the final infarct sizes respectively. A repeated measures analysis of variance and least significant difference post hoc test was used to compare the mean lesion volumes among ASL CBF, DSC T_max >4–6 s and final infarct.

Results

Mean patient age was 72.6 years. The average time from stroke onset to MRI was 13.9 hours. The ASL lesion volume showed significant correlation with the DSC lesion volume for T_max >4, 5 and 6 s (r = 0.81, 0.82 and 0.80; p<0.001). However, the mean lesion volume of ASL (50.1 ml) was significantly larger than those for T_max >5 s (29.2 ml, p<0.01) and T_max >6 s (21.8 ml, p<0.001), while the mean lesion volumes for T_max >5 or 6 s were close to mean final infarct size.

Conclusion

Quantitative measurement of ASL perfusion is well correlated with DSC perfusion. However, ASL perfusion may overestimate the perfusion defects and therefore further refinement of the true penumbra threshold and improved ASL technique are necessary before applying ASL in therapeutic trials.     

Vitreous and Plasma VEGF Levels as Predictive Factors in the Progression of Proliferative Diabetic Retinopathy after Vitrectomy

Purpose

To investigate the vitreous and plasma levels of vascular endothelial growth factor (VEGF) in patients with proliferative diabetic retinopathy (PDR) and to determine whether they predict a disease prognosis after primary vitrectomy.

Methods

Fifty patients (50 eyes) with PDR who underwent pars plana vitrectomy (PPV) and 56 healthy controls (56 eyes) were enrolled in this retrospective study. Clinical data were collected and analyzed. Vitreous and plasma VEGF concentrations were measured using enzyme-linked immunosorbent assays. VEGF levels and clinical data were compared and analyzed to see if they provide a prognosis of PDR progression after primary vitrectomy at more than 6 months follow-up. Correlation of VEGF concentrations between vitreous fluid and plasma was analyzed.

Results

The average BCVA was significantly improved after surgery (P<0.001). Vitreous and plasma VEGF levels were significantly elevated in PDR patients than those in healthy controls (P _vitreous<0.001; P _plasma<0.001). Both vitreous and plasma VEGF levels were significantly higher in PDR progression group than in stable group (P _vitreous<0.001; P _plasma = 0.004). Multivariate logistic regression analyses showed that the increased vitreous VEGF level was associated with the progression of PDR after primary PPV (OR = 1.539; P = 0.036). Vitreous VEGF level was positively associated with plasma VEGF level in PDR patients (P<0.001).

Conclusion

The increased VEGF level in vitreous fluid may be identified as a significant predictive factor for the outcome of vitrectomy in patients with PDR.     

Higher Gravidity and Parity Are Associated with Increased Prevalence of Metabolic Syndrome among Rural Bangladeshi Women

Background

Parity increases the risk for coronary heart disease; however, its association with metabolic syndrome among women in low-income countries is still unknown.

Objective

This study investigates the association between parity or gravidity and metabolic syndrome in rural Bangladeshi women.

Methods

A cross-sectional study was conducted in 1,219 women aged 15–75 years from rural Bangladesh. Metabolic syndrome was defined according to the standard NCEP-ATP III criteria. Logistic regression was used to estimate the association between parity and gravidity and metabolic syndrome, with adjustment of potential confounding variables.

Results

Subjects with the highest gravidity (> = 4) had 1.66 times higher odds of having metabolic syndrome compared to those in the lowest gravidity (0-1) (P _trend = 0.02). A similar association was found between parity and metabolic syndrome (P _trend = 0.04), i.e., subjects in the highest parity (> = 4) had 1.65 times higher odds of having metabolic syndrome compared to those in the lowest parity (0-1). This positive association of parity and gravidity with metabolic syndrome was confined to pre-menopausal women (P _trend <0.01). Among the components of metabolic syndrome only high blood pressure showed positive association with parity and gravidity (P _trend = 0.01 and <0.001). Neither Parity nor gravidity was appreciably associated with other components of metabolic syndrome.

Conclusions

Multi parity or gravidity may be a risk factor for metabolic syndrome.     

Association between Kidney Function and Framingham Global Cardiovascular Disease Risk Score: A Chinese Longitudinal Study

Background

Chronic kidney disease (CKD) is generally considered an independent risk factor for cardiovascular disease (CVD) development, but rates in individuals with estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m² are uncertain. The Framingham global CVD risk score (FRS) equation is a widely accepted tool used to predict CVD risk in the general population. The purpose of the present study was to examine whether an association exists between eGFR and FRS in a Chinese population with no CKD or CVD.

Methods

A total of 333 participants were divided into three groups based on FRS. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and CKD-EPI equation for Asians (CKD-EPI-ASIA) were used to measure eGFR.

Results

A significant inverse association between eGFR and FRS was confirmed with Pearson correlation coefficients of –0.669, –0.698 (eGFR_CKD-EPI, P<0.01) and –0.658, –0.690 (eGFR_CKD-EPI-ASIA, P<0.01). This association gradually diminished with progression from the low- to high-risk groups (eGFR_CKD-EPI, r = –0.615, –0.282, –0.197, P<0.01, P<0.01, P>0.05; similar results according to the CKD-EPI-ASIA equation). In the low- or moderate-risk new-groups, this association became stronger with increased FRS (eGFR_CKD-EPI-ASIA, r = –0557, –0.622 or –0.326, –0.329, P<0.01). In contrast to the results from 2008, eGFR was independently associated with FRS following adjustment for traditional cardiovascular risk factors (P<0.05).

Conclusion

Renal function has multiple influences on predicting CVD risk in various populations. With increasing FRS and decreasing eGFR, it is also independently associated with CVD, even in individuals with eGFR >60 ml/min/1.73 m².     

Surgical Decompression of Painful Diabetic Peripheral Neuropathy: The Role of Pain Distribution

Objective

To investigate the effect of surgical decompression on painful diabetic peripheral neuropathy (DPN) patients and discuss the role which pain distribution and characterization play in the management of painful DPN as well as the underlying mechanism involved.

Methods

A total of 306 patients with painful diabetic lower-extremity neuropathy were treated with Dellon surgical nerve decompression in our department. Clinical evaluation including Visual analogue scale (VAS), Brief Pain Inventory Short Form for diabetic peripheral neuropathy (BPI-DPN) questionnaire, two-point discrimination (2-PD), nerve conduction velocity (NCV) and high-resolution ultrasonography (cross-sectional area, CSA) were performed in all cases preoperatively, and at 6 month intervals for 2 years post-decompression. The patients who underwent surgery were retrospectively assigned into two subgroups (focal and diffuse pain) according to the distribution of the diabetic neuropathic pain. The control group included 92 painful DPN patients without surgery.

Results

The levels of VAS, scores in BPI-DPN, 2-PD, NCV results and CSA were all improved in surgical group when compared to the control group (P<0.05). More improvement of VAS, scores in BPI-DPN and CSA was observed in focal pain group than that in diffuse group (P<0.05).

Conclusions

Efficacy of decompression of multiple lower-extremity peripheral nerves in patients with painful diabetic neuropathy was confirmed in this study. While both focal and diffuse group could benefit from surgical decompression, pain relief and morphological restoration could be better achieved in focal group.     

The natural organosulfur compound dipropyltetrasulfide prevents HOCl-induced systemic sclerosis in the mouse

Introduction

The aim of this study was to test the naturally occurring organosulfur compound dipropyltetrasulfide (DPTTS), found in plants, which has antibiotic and anticancer properties, as a treatment for HOCl-induced systemic sclerosis in the mouse.

Methods

The prooxidative, antiproliferative, and cytotoxic effects of DPTTS were evaluated ex vivo on fibroblasts from normal and HOCl mice. In vivo, the antifibrotic and immunomodulating properties of DPTTS were evaluated in the skin and lungs of HOCl mice.

Results

H₂O₂ production was higher in fibroblasts derived from HOCl mice than in normal fibroblasts (P < 0.05). DPTTS did not increase H₂O₂ production in normal fibroblasts, but DPTTS dose-dependently increased H₂O₂ production in HOCl fibroblasts (P < 0.001 with 40 μM DPTTS). Because H₂O₂ reached a lethal threshold in cells from HOCl mice, the antiproliferative, cytotoxic, and proapoptotic effects of DPTTS were significantly higher in HOCl fibroblasts than for normal fibroblasts. In vivo, DPTTS decreased dermal thickness (P < 0.001), collagen content in skin (P < 0.01) and lungs (P < 0.05), αSMA (P < 0.01) and pSMAD2/3 (P < 0.01) expression in skin, formation of advanced oxidation protein products and anti-DNA topoisomerase-1 antibodies in serum (P < 0.05) versus untreated HOCl mice. Moreover, in HOCl mice, DPTTS reduced splenic B-cell counts (P < 0.01), the proliferative rates of B-splenocytes stimulated by lipopolysaccharide (P < 0.05), and T-splenocytes stimulated by anti-CD3/CD28 mAb (P < 0.001). Ex vivo, it also reduced the production of IL-4 and IL-13 by activated T cells (P < 0.05 in both cases).

Conclusions

The natural organosulfur compound DPTTS prevents skin and lung fibrosis in the mouse through the selective killing of diseased fibroblasts and its immunomodulating properties. DPTTS may be a potential treatment for systemic sclerosis.     

Psoriatic arthritis and sacroiliitis are associated with increased vascular inflammation by 18-fluorodeoxyglucose positron emission tomography computed tomography: baseline report from the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative

Introduction

Psoriasis and psoriatic arthritis (PsA) increase cardiovascular disease (CVD) risk, but surrogate markers for CVD in these disorders are inadequate. Because the presence of sacroiliitis may portend more severe PsA, we hypothesized that sacroiliitis defined by computed tomography (CT) would be associated with increased vascular inflammation defined by 18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), which is an established measure of CVD.

Methods

Participants (n = 65) underwent whole-body FDG-PET/CT. Metabolic activity of the aorta was measured using the maximal standardized uptake value (SUV_max), a measure of atherosclerotic plaque activity. The primary outcome was aortic vascular inflammation. Linear regression (with β-coefficients (β) and P-values reported for PsA and sacroiliitis) was used to adjust for CVD risk factors to determine associations of PsA or sacroiliitis with vascular inflammation. Likelihood ratio testing was performed to evaluate the contribution of sacroiliitis to vascular disease estimation compared to the effects of PsA and traditional CVD risk factors.

Results

Vascular inflammation (measured as SUV_max) was greater (P < 0.001) in patients with sacroiliitis (mean ± SD = 7.33 ± 2.09) defined by CT compared to those without sacroiliitis (6.39 ± 1.49, P = 0.038). There were associations between PsA and aortic inflammation (β = 0.124, P < 0.001) and between sacroiliitis and aortic inflammation (β = 0.270, P < 0.001) after adjusting for CVD risk factors. Sacroiliitis predicted vascular inflammation beyond PsA and CVD risk factors (χ² = 124.6, P < 0.001).

Conclusions

Sacroiliitis is associated with increased vascular inflammation detected by FDG-PET/CT, suggesting that sacroiliac joint disease may identify patients at greater risk for CVD. Large, ongoing prospective studies are required to confirm these findings.

Electronic supplementary material

The online version of this article (doi:10.1186/ar4676) contains supplementary material, which is available to authorized users.     

Tendon vibration attenuates superficial venous vessel response of the resting limb during static arm exercise

Background

The superficial vein of the resting limb constricts sympathetically during exercise. Central command is the one of the neural mechanisms that controls the cardiovascular response to exercise. However, it is not clear whether central command contributes to venous vessel response during exercise. Tendon vibration during static elbow flexion causes primary muscle spindle afferents, such that a lower central command is required to achieve a given force without altering muscle force. The purpose of this study was therefore to investigate whether a reduction in central command during static exercise with tendon vibration influences the superficial venous vessel response in the resting limb.

Methods

Eleven subjects performed static elbow flexion at 35% of maximal voluntary contraction with (EX + VIB) and without (EX) vibration of the biceps brachii tendon. The heart rate, mean arterial pressure, and rating of perceived exertion (RPE) in overall and exercising muscle were measured. The cross-sectional area (CSA_vein) and blood velocity of the basilic vein in the resting upper arm were assessed by ultrasound, and blood flow (BF_vein) was calculated using both variables.

Results

Muscle tension during exercise was similar between EX and EX + VIB. However, RPEs at EX + VIB were lower than those at EX (P <0.05). Increases in heart rate and mean arterial pressure during exercise at EX + VIB were also lower than those at EX (P <0.05). CSA_vein in the resting limb at EX decreased during exercise from baseline (P <0.05), but CSA_vein at EX + VIB did not change during exercise. CSA_vein during exercise at EX was smaller than that at EX + VIB (P <0.05). However, BF_vein did not change during the protocol under either condition. The decreases in circulatory response and RPEs during EX + VIB, despite identical muscle tension, showed that activation of central command was less during EX + VIB than during EX. Abolishment of the decrease in CSA_vein during exercise at EX + VIB may thus have been caused by a lower level of central command at EX + VIB rather than EX.

Conclusion

Diminished central command induced by tendon vibration may attenuate the superficial venous vessel response of the resting limb during sustained static arm exercise.     

Seroprevalence of Merkel Cell Polyomavirus in the General Rural Population of Anyang,China

Background

Despite the probably causal link between Merkel cell polyomavirus (MCPyV) infection and Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy, little is known about the seroepidemiology of MCPyV among healthy adults in China.

Methods

Serum antibodies against MCPyV were evaluated by multiplex serology in a population-based study of 5548 adults (including 1587 heterosexual couples) aged 25–65 years who were enrolled from rural Anyang, China in 2007–2009. Univariate and multivariate logistic regression analyses were performed to assess the risk factors for the seropositivity of MCPyV.

Results

The seroprevalence for MCPyV was 61.0%. MCPyV seropositivity was significantly higher in males than in females (64.5% vs. 57.7%, P<0.001), and for both genders, showed a trend of increase with age (Male: P _trend<0.001; Female: P _trend<0.001). Furthermore, among antibody positives, antibody levels of MCPyV increased with advancing age (P _trend = 0.017). MCPyV seropositivity of one spouse was significantly associated with that of the other partner (Adjusted OR = 1.32, 95% CI: 1.07–1.62). However, there was no association between sexual behaviors and the seropositivity of MCPyV.

Conclusions

High seroprevalence of MCPyV was observed in healthy Chinese individuals. Serological evidence suggests that nonsexual horizontal spread of MCPyV can occur among family members, and further research in this regard is needed.     

Elbow Flexion Contractures in Childhood in Obstetric Brachial Plexus Lesions: A Longitudinal Study of 20 Neurosurgically Reconstructed Infants with 8-Year Follow-up

Objective

 Little knowledge exists on the development of elbow flexion contractures in children with obstetrical brachial plexus lesion (OBPL). This study aims to evaluate the prognostic significance of several neuromuscular parameters in infants with OBPL regarding the later development of elbow flexion contractures.

Methods

 Twenty infants with OBPL with insufficient signs of recovery in the first months of life who were neurosurgically reconstructed were included. At a mean age of 4.6 months, the following neuromuscular parameters were assessed: existence of flexion contractures, cross-sectional area (CSA) of upper arm muscles on MRI, Narakas classification, EMG results, and elbow muscle function using the Gilbert score. In childhood at follow-up at mean age of 7.7 years, we measured the amount of flexion contractures and the upper arm peak force (Newton). Statistical analysis is used to assess relations between these parameters.

Results

 Flexion contractures of greater than 10 degrees occurred in 55% of our patient group. The relation between the parameters in infancy and the flexion contractures in childhood is almost nonexistent. Only the Narakas classification was related to the development of flexion contractures in childhood (p = 0.006). Infant muscle CSA is related to childhood peak muscle force.

Conclusion

 The role of infancy upper arm muscle hypotrophy/hypertrophy, reinnervation, and early elbow muscle function in the development of childhood elbow contractures remains unclear. In this cohort prediction of childhood flexion, contractures were not possible using infancy neuromuscular parameters. We suggest that contractures might be an adaptive process to optimize residual muscle function.     

Gated F-18 FDG PET for Assessment of Left Ventricular Volumes and Ejection Fraction Using QGS and 4D-MSPECT in Patients with Heart Failure: A Comparison with Cardiac MRI

Purpose

Ventricular function is a powerful predictor of survival in patients with heart failure (HF). However, studies characterizing gated F-18 FDG PET for the assessment of the cardiac function are rare. The aim of this study was to prospectively compare gated F-18 FDG PET and cardiac MRI for the assessment of ventricular volume and ejection fraction (EF) in patients with HF.

Methods

Eighty-nine patients with diagnosed HF who underwent both gated F-18 FDG PET/CT and cardiac MRI within 3 days were included in the analysis. Left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), and EF were obtained from gated F-18 FDG PET/CT using the Quantitative Gated SPECT (QGS) and 4D-MSPECT software.

Results

LV EDV and LV ESV measured by QGS were significantly lower than those measured by cardiac MRI (both P<0.0001). In contrast, the corresponding values for LV EDV for 4D-MSPECT were comparable, and LV ESV was underestimated with borderline significance compared with cardiac MRI (P = 0.047). LV EF measured by QGS and cardiac MRI showed no significant differences, whereas the corresponding values for 4D-MSPECT were lower than for cardiac MRI (P<0.0001). The correlations of LV EDV, LV ESV, and LV EF between gated F-18 FDG PET/CT and cardiac MRI were excellent for both QGS (r = 0.92, 0.92, and 0.76, respectively) and 4D-MSPECT (r = 0.93, 0.94, and 0.75, respectively). However, Bland-Altman analysis revealed a significant systemic error, where LV EDV (−27.9±37.0 mL) and ESV (−18.6±33.8 mL) were underestimated by QGS.

Conclusion

Despite the observation that gated F-18 FDG PET/CT were well correlated with cardiac MRI for assessing LV function, variation was observed between the two imaging modalities, and so these imaging techniques should not be used interchangeably.     

XPF-673C>T Polymorphism Effect on the Susceptibility to Esophageal Cancer in Chinese Population

Purpose

Xeroderma pigmentsum group F (XPF) plays a pivotal role in DNA nucleotide excision repair and has been linked to the development of various cancers. This study aims to assess the association of XPF genetic variants with the susceptibility to esophageal squamous cell carcinoma (ESCC) in Chinese population.

Methods

This two-stage case-control study was conducted in a total of 1524 patients with ESCC and 1524 controls. Genotype of XPF -673C>T and 11985A>G variants were determined by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Logistic regression analysis was performed to estimate odd ratios (ORs) and 95% confidence intervals (95% CI).

Results

Our case-control study showed that XPF -673TT genotype was associated with a decreased risk of ESCC compared with CC genotype in both case-control sets (Tangshan set: OR = 0.58; 95%CI = 0.34–0.99, P = 0.040; Beijing set: OR = 0.66; 95%CI = 0.46–0.95, P = 0.027). Stratified analyses revealed that a multiplicative interaction between -673C>T variant and age, sex or smoking status was evident (Gene-age: P_interaction = 0.002; Gene-sex: P_interaction = 0.002; Gene-smoking: P_interaction = 0.002). For XPF 11985A>G polymorphism, there was no significant difference of genotype distribution between ESCC cases and controls.

Conclusion

These findings indicated that genetic variants in XPF might contribute to the susceptibility to ESCC.     

Low-Level Carotid Baroreceptor Stimulation Suppresses Ventricular Arrhythmias during Acute Ischemia

Background

The autonomic imbalance during acute ischemia is involved in the occurrence of life-threatening arrhythmias.

Objective

To investigate the effect of autonomic nervous system (ANS) modulation by low-level carotid baroreceptor stimulation (LL-CBS) on ventricular ischemia arrhythmias.

Methods

Anesthetized dogs were received either sham treatment (SHAM group, n = 10) or LL-CBS treatment (LL-CBS group, n = 10). The voltage lowering the blood pressure was used as the threshold for setting LL-CBS at 80% below the threshold. Treatment started 1 hour before left anterior descending coronary (LAD) occlusion, and continued until the end of experience. Ventricular effective refractory periods (ERP), monophasic action potential duration at 90% (APD₉₀), ventricular arrhythmias, indices of heart rate variability, left stellate ganglion nerve activity (LSGNA) and infarct sizes were measured and analyzed.

Results

Ventricular ischemia resulted in an acute reduction of blood pressure, which was not significantly affected by LL-CBS. After 1 hour of LL-CBS, there was a progressive and significant increase in ERP, increase in APD₉₀, and decrease in LSGNA vs the SHAM group (all P<0.05). LL-CBS apparently reduced premature ventricular contractions (PVC, 264±165 in the SHAM group vs 60±37 in the LL-CBS group; P<0.01) during LAD occlusion. Number of episodes of ventricular fibrillation (VF) was 8 in the Control group versus 3 in the LL-CBS group (80% versus 30%, P<0.05). LL-CBS obviously increased high frequency (HF) component (P<0.05) and decreased low frequency/high frequency ratio (P<0.05) compared with the SHAM group. Ischemic size was not affected by LL-CBS between the two groups.

Conclusions

LL-CBS reduced the occurrences of ventricular arrhythmias during acute ischemia without affecting blood pressure. The procedure was associated with changes of electrophysiological characteristics, nerve activity and heart rate variability. Therefore, LL-CBS may protect from ventricular arrhythmias during acute ischemic events by modulating ANS.     

Magnetic Resonance Evaluation of Multiple Myeloma at 3.0 Tesla: How Do Bone Marrow Plasma Cell Percentage and Selection of Protocols Affect Lesion Conspicuity?

Purpose

To compare various pulse sequences in terms of percent contrast and contrast-to-noise ratio (CNR) for detection of focal multiple myeloma lesions and to assess the dependence of lesion conspicuity on the bone marrow plasma cell percent (BMPC%).

Materials and Methods

Sagittal T₁-weighted FSE, fat-suppressed T₂-weighted FSE (FS- T₂ FSE), fast STIR and iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) imaging of the lumbar spine were performed (n = 45). Bone marrow (BM)-focal myeloma lesion percent contrast and CNR were calculated. Spearman rank correlation coefficients were obtained between percent contrast, CNR and BMPC%. Percent contrasts and CNRs were compared among the three imaging sequences.

Results

BM-focal lesion percent contrasts, CNRs and BMPC% showed significant negative correlations in the three fat-suppression techniques. Percent contrast and CNRs were significantly higher for FS- T2 FSE than for STIR (P<0.01, P<0.05, respectively), but no significant differences were found among the three fat-suppression methods in the low tumor load BM group.

Conclusion

The higher BMPC% was within BM, the less conspicuous the focal lesion was on fat-suppressed MRI. The most effective protocol for detecting focal lesions was FS- T₂ FSE. In the high tumor load BM group, no significant differences in lesion conspicuity were identified among the three fat-suppression techniques.     

Hepatitis C Virus Infection Influences the S-Methadone Metabolite Plasma Concentration

Background and Objectives

Heroin-dependent patients typically contract hepatitis C virus (HCV) at a disproportionately high level due to needle exchange. The liver is the primary target organ of HCV infection and also the main organ responsible for drug metabolism. Methadone maintenance treatment (MMT) is a major treatment regimen for opioid dependence. HCV infection may affect methadone metabolism but this has rarely been studied. In our current study, we aimed to test the hypothesis that HCV may influence the methadone dosage and its plasma metabolite concentrations in a MMT cohort from Taiwan.

Methods

A total of 366 MMT patients were recruited. The levels of plasma hepatitis B virus (HBV), HCV, human immunodeficiency virus (HIV) antibodies (Ab), liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) were measured along with the urine morphine concentration and amphetamine screening.

Results

Of the 352 subjects in our cohort with HCV test records, 95% were found to be positive for plasma anti-HCV antibody. The liver functional parameters of AST (Wilcoxon Rank-Sum test, P = 0.02) and ALT (Wilcoxon Rank-Sum test, P = 0.04), the plasma methadone concentrations (Wilcoxon Rank-Sum test, P = 0.043) and the R-enantiomer of methadone concentrations (Wilcoxon Rank-Sum test, P = 0.032) were significantly higher in the HCV antibody-positive subjects than in the HCV antibody-negative patients, but not the S-EDDP/methadone dose ratio. The HCV levels correlated with the methadone dose ( = 14.65 and 14.13; P = 0.029 and 0.03) and the S-EDDP/methadone dose ratio ( = −0.41 and −0.40; P = 0.00084 and 0.002) in both univariate and multivariate regression analyses.

Conclusions

We conclude that HCV may influence the methadone dose and plasma S-EDDP/methadone dose ratio in MMT patients in this preliminary study.     

Maternal Vitamin D Status in Preeclampsia: Seasonal Changes Are Not Influenced by Placental Gene Expression of Vitamin D Metabolizing Enzymes

Preeclampsia, a hypertensive disorder in pregnancy develops in 2–8% of pregnancies worldwide. Winter season and vitamin D deficiency have been associated with its onset.

Objective

To investigate the influence of season on maternal vitamin D status and placental vitamin D metabolism.

Methods

25-OH vitamin D and 1,25-(OH)₂ vitamin D were measured in maternal serum obtained during the winter or summer months from 63 pregnant women at delivery (43 healthy, 20 preeclampsia). In a subgroup, mRNA expression of CYP24A1 (24-hydroxylase), CYP27B1 (1α-hydroxylase) and VDR (vitamin D receptor) were quantified by real time PCR in placental samples of 14 women with normal pregnancies and 13 with preeclampsia.

Results

In patients with preeclampsia,25-OH vitamin D levels were lower, but differed significantly from controls only in summer (18.21±17.1 vs 49.2±29.2 ng/mL, P<0.001), whereas 1,25-(OH)₂ vitamin D levels were significantly lower only in winter (291±217 vs 612.3±455 pmol/mL, P<0.05). A two-factorial analysis of variance produced a statistically significant model (P<0.0001) with an effect of season (P<0.01) and preeclampsia (P = 0.01) on maternal 25-OH vitamin D levels, as well as a significant interaction between the two variables (P = 0.02). Placental gene expression of CYP24A1, CYP27B1, and VDR did not differ between groups or seasons. A negative correlation between placental gene expression of CYP24A1 and CYP27B1 was observed only in healthy controls (r = −0.81, P<0.0001).

Summary

Patients with preeclampsia displayed lower vitamin D serum levels in response to seasonal changes.The regulation of placental CYP24A1, but not of the VDR or CYP27B1 might be altered in preeclampsia.