Mannose-binding lectin and susceptibility to infection in Chinese patients with systemic lupus erythematosus

OBJECTIVE: To test the hypothesis that low serum mannose-binding lectin (MBL) levels, as a result of the single-nucleotide polymorphisms in the promoter region (-221 X/Y) and exon 1 (codon 54 A/B) of the MBL2 gene, predispose to infection in Chinese patients with systemic lupus erythematosus (SLE). METHODS: Two hundred forty-five patients with SLE were prospectively followed for the development of major infective episodes that required hospitalization and antibiotic treatment during 1992-2005. MBL genotypes were determined by polymerase chain reaction and serum MBL levels were measured by ELISA. RESULTS: In total, 254 major infections developed in 130 patients. Serum MBL levels were shown to correlate inversely with the number of bacterial infections (r = -0.13, p = 0.03). The distribution of MBL genotypes was similar in patients with and without major infection (p = 0.84). Patients with major infection also had more major lupus exacerbations that required daily prednisolone dose > or = 15 mg. Logistic regression showed that log MBL level (odds ratio 0.516, 95% confidence interval 0.305-0.873; p = 0.01) and major lupus exacerbation (OR 1.382, 95% CI 1.154-1.654; p < 0.001) were independent risk factors to major bacterial infection after adjustment for age and disease duration. Multiple regression analysis showed an increase in risk of bacterial infection by 34.2% for every decrease in serum MBL level by one log, and by 22.8% for each increase in number of major lupus exacerbations. CONCLUSION: Low serum MBL level predisposes Chinese patients with SLE to more major infections, in particular bacterial ones.     

CTA contrast enhancement of the aorta and pulmonary artery: the effect of saline chase injected at two different rates in a canine experimental model

OBJECTIVE: To investigate the effect of saline chase injected at 2 different rates on computed tomography (CT) angiography. MATERIALS AND METHODS: This study was approved by our institutional animal study committee. Three injection protocols were used; contrast injection (24 mL, 0.8 mL/s) without saline chase (protocol A), contrast injection with saline chase injected at the same rate as the contrast medium (protocol B), and contrast injection with saline chase injected at half the rate (0.4 mL/s) of the contrast medium (protocol C). In the 3 dogs used in our study, each of the protocols was applied twice for every dog resulting in a total of 18 sessions of monitoring scans. CT images were acquired every second at the fixed level of the aorta and pulmonary artery (PA). The duration of plateau, plateau deviation, and peak arterial enhancement were computed and compared using the Kruskall-Wallis and Mann-Whitney U test. RESULTS: Peak contrast enhancements were significantly more delayed with protocol B than with protocol A in both the PA (B: 48 seconds, A: 30 seconds, P=0.024) and aorta (B: 46 seconds, A: 38 seconds, P=0.024). The duration of enhancement plateau was longer with protocol B than with protocol A in PA (B: 14.8 seconds, A: 9.0 seconds, P=0.002) and in aorta (B: 16.2 seconds, A: 11.6 seconds, P=0.004). Protocol C had the longest duration of plateau in both PA (34.5 seconds, P=0.002) and aorta (33.8 seconds, P=0.004) with uniform plateau enhancement. The peak enhancement values of protocol C, however, were substantially lower than that of protocol A and B in both the PA (A: 262 HU, B: 239 HU, C: 191 HU, P=0.001) and aorta (A: 263 HU, B: 268 HU, C: 210 HU, P=0.001). CONCLUSIONS: Saline chase prolongs the duration of plateau and delays peak enhancement of the pulmonary artery and aorta. Saline chase injected at half the rate of contrast medium injection allowed more uniform and prolonged plateau contrast enhancement than other protocols.     

Sonographic findings in a model of ischemia-induced necrotizing enterocolitis with pathological correlations

PURPOSE: To evaluate sonographic findings in ischemic enterocolitis (IEC) and correlate with pathologic findings in an experimental study. MATERIALS AND METHODS: Ischemic enterocolitis was induced with ligation of the superior mesenteric artery in 20 rabbits. Plain radiography and ultrasonography (US) were performed. US was done hourly after the ligation using 10 MHz linear probe. US findings were categorized into 2 groups according to the bowel wall echogenicity; the echogenic dots (ED) group and the circumferential granular echogenicity (CGE) group. US findings were compared with the specimen radiography and the histopathology. RESULTS: On US, ED were seen in the bowel of all rabbits after SMA ligation (2.2 +/- 1.3 hours [standard deviation]) and CGE in 16 rabbits (4.1 +/- 0.9 hours). On the specimen radiographs, multiple radiolucent air bubbles were present. Comparing the ED and CGE group, histopathological findings revealed the CGE group had severer injury of the bowel wall than the ED group. On plain radiography, there was progressive bowel distention, but pneumatosis intestinalis (PI) was not evident. CONCLUSION: ED or CGE are the sonographic findings of ischemic enterocolitis, and bowel wall echogenicity might reflect the degree of ischemic injury.     

Hepatic arterial diameter measured with US: adjunct for US diagnosis of biliary atresia

PURPOSE: To prospectively evaluate the accuracy of hepatic artery diameter and hepatic artery diameter-to-portal vein diameter ratio for ultrasonographic (US) diagnosis of biliary atresia, with cholangiographic or clinical information as reference standard. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. US was performed in 68 neonates and infants with cholestatic jaundice (mean age, 61 days; male-to-female ratio, 38:30). Biliary atresia (n = 38) was confirmed with cholangiography, and hepatitis (n = 30) was diagnosed with clinical (n = 24) or cholangiographic (n = 6) findings. Diameter of the right hepatic artery was measured with US. Right hepatic artery diameter-to-right portal vein diameter ratio was measured to determine relative enlargement of the hepatic artery. As a control group, 17 neonates and infants (mean age, 67 days; male-to-female ratio, 12:5) without jaundice underwent US of the porta hepatis. Statistical analysis was performed to compare US parameters among three groups with one-way analysis of variance. Optimal cutoff values of the hepatic artery diameter and hepatic artery diameter-to-portal vein diameter ratio for biliary atresia diagnosis were obtained with receiver operating characteristic analysis. RESULTS: The diameter of the right hepatic artery in biliary atresia group (1.9 mm +/- 0.4 [standard deviation]) was significantly larger than that in the hepatitis (1.4 mm +/- 0.3) and control (1.2 mm +/- 0.2) groups (P < .001). Hepatic artery diameter-to-portal vein diameter ratio in the biliary atresia group (0.52 +/- 0.12) was larger than that in hepatitis (0.40 +/- 0.07) and in control (0.40 +/- 0.10) groups (P < .001). Optimum cutoff values for diagnosis of biliary atresia were 1.5 mm (sensitivity, 92%; specificity, 87%; accuracy, 89%) for hepatic artery diameter and 0.45 for hepatic artery diameter-to-portal vein diameter ratio (sensitivity, 76%; specificity, 79%; accuracy, 78%). CONCLUSION: Measurement of hepatic artery diameter can be helpful in the US diagnosis of biliary atresia.     

Focal interstitial fibrosis manifesting as nodular ground-glass opacity: thin-section CT findings

The purpose of this study was to describe the thin-section computed tomographic (CT) features of focal interstitial fibrosis manifesting as nodular ground-glass opacity (GGO) and its changes during follow-up. The thin-section CT findings of pathologically proven focal interstitial fibrosis manifesting as nodular GGO were retrospectively evaluated in nine patients (five women and four men; mean age, 59.3 years; age range, 34–81 years). The thin-section CT findings of each lesion were analyzed for multiplicity, location, shape, margin characteristics, pleural retraction or vascular convergence, size and internal attenuation, lesion internal features and lesion changes on follow-up CT scans (mean 90 days, range 5 to 215 days). All lesions manifested as a solitary nodular GGO (100%), and seven of the nine lesions (77.8%) were located in the upper lobe. Focal interstitial fibrosis was round or oval in shape in five cases (55.6%), complex in shape in three cases (33.3%) and polygonal in one case (11.1%). Lesion margins were smooth in five patients (55.6%), irregular in three (33.3%) and spiculated in one (11.1%). Pleural retraction or vascular convergence was present in two patients (22.2%). Lesions measured 4.8 mm to 25.5 mm (mean, 11.5 mm) and had attenuations ranging from −151 to −699 HU (mean, −514.7 HU). Eight (88.9%) manifested as pure nodular GGOs and one as mixed GGO with a spiculated margin. In all patients, no lesion changes were observed in follow-up CT scans. Focal interstitial fibrosis manifesting as nodular GGO usually presents as a solitary nodule with pure GGO on thin-section CT, which does not change significantly during follow-up.     

Anterior Cruciate Ligament Tear: Reliability of MR Imaging to Predict Stability after Conservative Treatment

Objective

The aim of this study is to evaluate the reliability of MR imaging to predict the stability of the torn anterior cruciate ligament (ACL) after complete recovery of the ligament''s continuity.

Materials and Methods

Twenty patients with 20 knee injuries (13 males and 7 females; age range, 20-54) were enrolled in the study. The inclusion criteria were a positive history of acute trauma, diagnosis of the ACL tear by both the physical examination and the MR imaging at the initial presentation, conservative treatment, complete recovery of the continuity of the ligament on the follow up (FU) MR images and availability of the KT-2000 measurements. Two radiologists, who worked in consensus, graded the MR findings with using a 3-point system for the signal intensity, sharpness, straightness and the thickness of the healed ligament. The insufficiency of ACL was categorized into three groups according to the KT-2000 measurements. The statistic correlations between the grades of the MR findings and the degrees of ACL insufficiency were analyzed using the Cochran-Mantel-Haenszel test (p < 0.05).

Results

The p-values for each category of the MR findings according to the different groups of the KT-2000 measurements were 0.9180 for the MR signal intensity, 1.0000 for sharpness, 0.5038 for straightness and 0.2950 for thickness of the ACL. The MR findings were not significantly different between the different KT-2000 groups.

Conclusion

MR imaging itself is not a reliable examination to predict stability of the ACL rupture outcome, even when the MR images show an intact appearance of the ACL.     

Vaccination with Live Leishmania major and CpG DNA Promotes Interleukin-2 Production by Dermal Dendritic Cells and NK Cell Activation

Cutaneous leishmaniasis due to Leishmania major is an emerging, chronic parasitic disease that causes disfigurement and social stigmatization. Drug therapy is inadequate, and there is no vaccine. Inoculation of virulent parasites (leishmanization) is the only intervention that has ever provided protection, because it mimics natural infection and immunity, but it was discontinued due to safety concerns (uncontrolled vaccinal lesions). In an effort to retain the benefits (immunity) while avoiding the side effects (lesions) of leishmanization, we immunized C57BL/6 mice with L. major and CpG DNA (Lm/CpG). This combination prevented lesions while inducing immunity. Also, the vaccination with live parasites and the Toll-like receptor 9 agonist enhanced innate immune responses by activating dermal dendritic cells (DCs) to produce cytokines. Here we report that the Lm/CpG vaccine induced dermal DCs, but not bone marrow-derived DCs, to produce interleukin-2 (IL-2). The release of this unusual DC-derived cytokine was concomitant with a peak in numbers of NK cells that produced gamma interferon (IFN-γ) and also enhanced activation of proliferation of IFN-γ⁺ CD4⁺ T cells. Parasite growth was controlled in Lm/CpG-vaccinated animals. This is the first demonstration of the ability of dermal DCs to produce IL-2 and of the activation of NK cells by vaccination in the context of leishmaniasis. Understanding how the Lm/CpG vaccine enhances innate immunity may provide new tools to develop vaccines against L. major, other chronic infectious diseases, or other conditions, such as cancer.The leishmaniases are among the most important emerging parasitic diseases, second only to malaria in terms of the number of affected people. The prevalence of cutaneous leishmaniasis due to Leishmania major, a chronic disease leading to disfigurement, functional impairment, and social stigmatization, is estimated to be 2 million cases (4); recent data demonstrate that this number is greatly underestimated (1). Naïve individuals are very susceptible, leading to dramatic outbreaks. Current drugs are inadequate due to toxicity, resistance, cost, and adverse effects, and there is no vaccine. Thus, there is a clear need for both prophylactic and therapeutic control measures. Inoculation of virulent L. major (leishmanization), practiced in areas of leishmaniasis endemicity for more than 1,000 years, is the only strategy that has ever provided lifelong protection, because it mimics the natural infection, enabling parasite persistence and the subsequent concomitant immunity. It was widely applied but was discontinued due to the development of large vaccinal lesions in about 10% of the immunized patients (14).Because no vaccine other than leishmanization has been successful with humans, we work to understand its mechanism of action. In an effort to retain the benefits (immunity) while avoiding the side effects (lesions) of leishmanization, we immunized C57BL/6 mice with L. major alone or in combination with CpG DNA (Lm/CpG). Lm/CpG prevented vaccinal lesions while achieving L. major persistence and immunity (13, 29). Mechanistically, we found that Lm/CpG causes early activation of dermal dendritic cells (DCs) to produce interleukin-6 (IL-6), reducing the accumulation of regulatory T cells (Tregs) in the vaccination site (29). Activated DCs also produced IL-12, promoting activation and proliferation of gamma interferon (IFN-γ)-producing CD4⁺ T cells (13, 29). The lack of suppressors and the increase in effectors resulted in parasite killing and a lack of vaccinal lesions. Interestingly, Treg numbers recovered in the skin of mice vaccinated with Lm/CpG, enabling concomitant immunity and lifelong protection (13), as previously demonstrated by us (3).While continuing the study of the mechanism of action of the Lm/CpG vaccine, we detected a rapid increase in IL-2 expression in the vaccination site. IL-2 is a survival factor for B and T lymphocytes, but it is also necessary for DC-dependent NK cell activation (7). Thus, NK cells may be critical in the early control of parasite growth in the vaccinated mice. In this paper, we report the unusual IL-2 production by CD11c⁺ DCs in the skin of mice vaccinated with Lm/CpG. This unusual secretion is concomitant with a peak in IFN-γ-producing NK cells and CD4⁺ T cells and the control of parasite growth. Thus, vaccination with live parasites and Toll-like receptor 9 agonists appears to enhance not only adaptive immunity but also the response of innate immune cells to decrease parasite growth and the development of vaccinal pathology.     

Age Classes and Sex Differences in the Skull of the Mediterranean Monk Seal,Monachus monachus (Hermann, 1779). A study Based on Bone Shape and Density

This study analyzes morphometrically 17 skulls of the Mediterranean monk seal Monachus monachus housed in different Italian Museums and collections. We considered several morphometric variables (31 linear, 1 volumetric and 1 surface area measurements). In addition, we identified, measured and compared two nonmorphometric variables, namely, the bone densities of selected areas obtained using a dual‐energy X‐ray absorptiometry (DXA) device. The high correlation coefficient of all variables indicated continuous growth with the onset of age. The ranking of the hierarchical cluster analysis identified the presence of three main groups containing individuals of similar sizes: lactating pups and yearlings; subadult individuals and adult females; and adult males. Smaller groups were identified within these clusters, and their respective allocations into two subgroups were argued on the basis of skull development and other factors. The discriminant analysis of the three main groups indicated a discriminant diagnostic key, based on condilobasilar length (CBlr‐L); maximum mandibular branch height (MB‐H); and surface area of the bulla tympanica. The proposed diagnostic key is useful to classify monk seal skulls of unidentified age and sex. The data reported here suggest that in this species certain adult skull growth features (enhanced tympanic bullae surface area extension, occipital bone density) are sexually dimorphic and possibly related to specific anatomical functions. These functions may include an enhanced auditory capacity; an increased development of the cranial musculature capable of supporting a large skull and guaranteeing the mandibular strength necessary for mastication; and male to male social interactions. Anat Rec, 292:544–556, 2009. © 2009 Wiley‐Liss, Inc.     

抗抑郁剂治疗前后癫痫患者的认知障碍和情感障碍研究

目的探讨抗抑郁剂对癫痫患者认知功能和情感障碍的影响。方法收集癫痫患者320例,正常对照组56例。320例癫痫患者随机分为百忧解治疗组和常规治疗组(每组160例)。百忧解治疗组在常规抗癫痫治疗的同时加用百忧解抗抑郁治疗,每日20mg,连服12周。各组分别进行韦氏智能测定和情感测定,并应用事件相关电位P300、N400研究,对比分析癫痫患者认知功能和情感障碍的特征。结果320例癫痫患者中,智能水平低于正常者(IQ值≤90分)259例(80.9%),智能水平明显低下者(IQ值≤70分)168例(52.8%);246例(76.9%)伴有抑郁,283例(88.4%)伴有焦虑。联合应用抗癫痫药组认知障碍和情感障碍均较单药服药组严重。伴随着认知功能障碍和情感障碍,癫痫患者P300和N400的潜伏期明显延长、波幅降低。治疗12周后常规治疗组和百忧解治疗组认知功能和情感障碍均有改善,P300和N400潜伏期和波幅亦明显改善,且百忧解治疗组的改善更加明显。结论抗癫痫药可造成癫痫患者认知功能的损害,单药应用较联合用药对癫痫患者认知功能损害轻。伴随着认知功能障碍和情感障碍,癫痫患者P300和N400潜伏期明显延长、波幅降低。抗抑郁治疗可改善癫痫患者的认知功能。