Detection of Schistosoma mansoni circulating cathodic antigen for evaluation of resistance induced by irradiated cercariae.

The appearance of serum levels of circulating cathodic antigen (CCA) detectable by a monoclonal antibody (mAb) (5H11) antigen-capture sandwich enzyme-linked immunosorbent assay (ELISA) system was evaluated during acute Schistosoma mansoni infections in female CF1 mice exposed to either 100 or 25 cercariae. Measurable CCA levels occurred in these groups at 5 and 7 wk after infection, respectively. The kinetics of appearance of CCA were thus related to the intensity of infection. The level of resistance developed by female C57BL/6 mice upon immunization with irradiated cercariae, as expressed by both worm burden and CCA levels after cercarial challenge was evaluated. Immunization conferred 44% protection against the challenge infection, and the level of CCA detected in the sera of the control group was significantly (P less than 0.02) higher than that found in the sera of the immunized group, 6 wk after challenge. These results demonstrate that CCA detection by the 5H11 mAb antigen-capture sandwich ELISA can reflect vaccine-induced resistance against S. mansoni. Localization studies showed that 5H11 reacts with a CCA epitope in the adult worm gut and to a lesser extent with the male tegument. Adaptations of this and other antigen detection systems may prove useful in monitoring the efficacy of developmental vaccines, an ability that may be essential for the extension of such studies to humans.     

两种肠内营养方案对重症急性胰腺炎患者 肠道菌群及预后的影响

目的探讨肠内免疫微生态营养和免疫增强型肠内营养方案对重症急性胰腺炎患者肠道菌群及远期预后的影响。方法选择2014年1月至2017年6月在我院就诊的重症急性胰腺炎患者156例。按照随机数字表法将患者分为A组(肠内免疫微生态营养方案组)、B组(免疫增强型肠内营养方案组)和对照组(常规肠内营养方案组),各52例。检测患者治疗前后T淋巴细胞及其亚群NK细胞、B淋巴细胞,血清免疫球蛋白及ALB、TF、PA等营养指标。同时检测患者肠道菌群,判定3组患者肠道菌失调症发生率。治疗后对患者随访6个月,记录并发症及不良预后。结果治疗后A组和B组患者患者CD+4细胞、CD+8细胞、CD+4/CD+8、NK细胞、B淋巴细胞水平显著高于治疗前,对照组患者除CD+8细胞和NK细胞外,其余各细胞水平亦显著高于治疗前(P0.05),且A组和B组患者治疗后各细胞水平高于对照组(P0.05)。治疗后A组和B组患者IgA、IgG、IgM水平显著升高,且A组和B组高于对照组(P0.05),同时3组患者治疗后ALB水平显著高于治疗前,且A、B组高于对照组,但A组和B组治疗后ALB水平比较差异无统计学意义(P0.05)。发病7～10d后,A组患者菌群失调发生率为5.77%,低于B组(19.23%)和对照组(36.54%),两两比较差异均有统计学意义(P0.05)。治疗6个月后,A组患者出现1例胰腺及胰周感染,1例MODS,0例病死;B组出现1例胰腺及胰周感染,2例MODS,3例菌血症,1例腹腔感染,2例病死;对照组出现6例胰周胰腺感染,7例MODS,5例菌血症,3例腹腔感染,3例病死。A组和B组预后显著优于对照组,且A组预后优于B组(P0.05)。结论肠内免疫微生态营养与免疫增强型肠内营养均能显著提高重症急性胰腺炎患者营养状况,提高免疫水平,且肠内免疫微生态营养在改善肠道菌群及预后方面具有更好的效果,值得临床推广。     

双歧杆菌四联活菌片对急性胰腺炎患者血清内毒素和降钙素原水平的影响及疗效观察

目的探讨双歧杆菌四联活菌片对急性胰腺炎患者血清内毒素和降钙素原（PCT）水平的影响及疗效观察。方法将66例急性胰腺炎患者随机分为观察组和对照组。两组患者均予以禁食禁饮、持续胃肠减压、预防感染、抑酸、解痉镇痛、抑制胰酶分泌和纠正水电解质酸碱紊乱等常规治疗。观察组患者加用双歧杆菌四联活菌片1.5 g进行水化后自胃管灌注,夹管2 h,3次/d,对照组除不使用双歧杆菌四联活菌片外余治疗同观察组。观察两组患者治疗前后血清内毒素和PCT水平的变化,并比较其临床疗效。结果治疗7 d后,两组患者血清内毒素和PCT水平均有不同程度的下降（P〈0.05或P〈0.01）,且观察组下降值比对照组更明显（P〈0.05）;同时观察组临床总有效率为93.94%,明显高于对照组的75.76%（χ2=4.24,P〈0.05）。结论双歧杆菌四联活菌片辅助治疗急性胰腺炎具有较好疗效,能明显降低血清内毒素和PCT水平,减轻肠源性内毒素血症,对肠黏膜屏障功能具有良好的保护作用。     

Plasma interferon-gamma, interleukin-10 and soluble markers of immune activation in infants with primary adenovirus (ADV) and respiratory syncytial virus (RSV) infection

Adenovirus (ADV) and respiratory syncytial virus (RSV) are etiological agents of acute respiratory tract infection in infants. Long-term prognosis of ADV infection includes severe lung damage, bronchiectasis and hyperlucent lung, while RSV infection is associated with development of recurrent wheezing and subsequent asthma. These differences may be related to differences in the primary immune responses elicited by these viruses. In this paper, we investigated the type of cytokine responses and the magnitude of immune activation in ADV and RSV infections in infants. We examined plasma concentrations of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), soluble interleukin-2 receptor (sCD25) and soluble tumor necrosis factor receptor II (sTNFR-II) in previously healthy infants during the acute phase of primary ADV infection (n = 21) and RSV infection (n = 68), and in uninfected controls (n = 44). In ADV-infected infants, IFN-gamma plasma levels were significantly higher than those observed in RSV cases and the control group (p < 0.05). RSV cases did not show any differences in IFN-gamma plasma levels compared to the other groups. sCD25 levels were significantly higher in ADV- and RSV-infected infants than in controls (p < 0.0001), and higher in ADV than in RSV cases (p < 0.05). sTNFR-II levels were significantly higher in RSV- and ADV-infected infants than in controls (p < 0.0001, p < 0.05, respectively), and higher in RSV than in ADV infection (p < 0.05). No significant differences were observed in IL-10 plasma concentrations between the three groups. These results indicate that ADV and RSV infections in infants differ significantly with regard to the magnitude of production of interferon-gamma and soluble immune activation markers sCD25 and sTNFR-II. These immunological differences may be involved in the different clinical outcomes associated with these viral infections.     

幽门螺杆菌感染对过敏性紫癜患儿的影响

目的探讨幽门螺杆菌(H.pylori)感染对过敏性紫癜(henoch-schonlein purpura, HSP)患儿肠道菌群、疗效及疾病复发情况的影响。方法选取2017年1月至2018年6月我院收治的100例HSP患儿作为观察组,同时随机选取同时段于我院体检的100例健康儿童作为对照组。采用13C同位素呼吸试验法检测H.pylori感染情况,根据H.pylori感染情况进一步将观察组患儿分为感染组和非感染组。收集观察组患儿粪便样本,采用Illumina MiSeq平台对患儿肠道菌群的16S rRNA V4序列进行测序,分析肠道菌群组成,同时分析患儿疗效及疾病复发情况与H.pylori感染的关系。结果观察组患儿H.pylori感染率显著高于对照组(47.00%vs 30.00%,χ²=6.100,P=0.015)。治疗后非感染组患儿有效率明显高于感染组(92.45%vs 78.72%,χ²=3.900,P=0.048),复发率显著低于感染组(24.53%vs 44.68%,χ²=4.510,P=0.034)。感染组和非感染组患儿肠道菌群多样性差异无统计学意义,但在门、科水平上肠道菌群结构相对丰度差异有统计学意义。非感染组患儿肠道厚壁菌门、放线菌门相对丰度显著高于感染组,同时其拟杆菌科、瘤胃菌科、链球菌科、双歧杆菌科、巴斯德菌科相对丰度也显著高于感染组(均P<0.05)。结论 H.pylori感染与儿童HSP的发生存在一定相关性。H.pylori感染可影响HSP患儿肠道菌群组成,同时降低疾病治疗效果以及增加复发风险。     

Hcy, hs-CRP与急性脑梗死患者颈动脉粥样硬化关系的研究

目的:探讨急性脑梗死患者血清同型半胱氨酸(Hcy)、超敏C反应蛋白(hs-CRP)与颈动脉粥样硬化的相关性及临床意义。方法:收集确诊为急性脑梗死患者90例,对患者进行颈动脉超声检查,根据颈动脉狭窄程度将患者分成颈动脉内膜正常组、轻度狭窄组、中-重度狭窄组。比较三组患者斑块检出率、Hcy、hs-CRP水平和IMT厚度,同时对Hcy、hs-CRP与IMT进行相关性分析。结果:中-重度狭窄组斑块检出率为86.4%,显著高于轻度狭窄组和颈动脉内膜正常组(P0.05);颈动脉内膜正常组Hcy、hs-CRP水平以及IMT厚度均显著低于颈动脉轻度狭窄组、中-重度狭窄组(P0.05);hs-CRP与IMT呈正相关(r=0.71,P0.05);Hcy与IMT呈正相关(r=0.79,P0.05)。结论:血清Hcy和hs-CRP水平与颈动脉粥样硬化程度密切相关,Hcy、hs-CRP联合检测对急性脑梗死的早期诊断和预后有着重要临床意义。     

肠道菌群失衡与急性胰腺炎易位感染的关系

目的探讨急性胰腺炎患者肠道菌群与胰腺炎易位感染的关系。方法前瞻性地募集重症急性胰腺炎患者171名,根据是否发生易位感染,分为急性胰腺炎非感染组(131名)和急性胰腺炎易位感染组(40名),所有入选者入院时收集粪便标本和血清,分别采用实时荧光定量PCR和分光光度法测定肠道菌群组成及肠道屏障功能,探讨肠道菌群与胰腺炎肠道屏障以及易位感染的关系。结果急性胰腺炎易位感染组患者入院时肠道菌群中的肠杆菌以及肠球菌含量较非感染组显著增加,实时荧光定量PCR结果发现感染组患者潜在致病菌如肠球菌、肠杆菌显著高于非感染组,与肠道黏膜屏障功能的内毒素水平、二胺氧化酶活性以及D-乳酸含量显著正相关,而双歧杆菌显著低于非感染组,与内毒素水平、二胺氧化酶活性以及D-乳酸含量显著负相关,结果提示肠道菌群失衡可能是急性胰腺炎易位感染发生的主要原因之一。结论肠道菌群失衡是急性胰腺炎易位感染发生的高危因素,与急性胰腺炎易位感染发生相关。     

Lipids and carotid plaque in the Northern Manhattan Study (NOMAS)

Background

Heterogeneity in B-type natriuretic peptide (BNP) levels, especially among individuals with acute heart failure with normal left ventricular ejection fraction (HFNEF), can cause confusion in interpreting results. We investigated the characteristics of cases of acute HFNEF with only modestly elevated BNP.

Methods

One hundred forty-two patients with acute or acute exacerbation of chronic HFNEF were divided into two groups by BNP level: BNP < 100 pg/ml (NB group, n = 45) and BNP ≥ 100 pg/ml (B group, n = 97). We compared clinical findings, echocardiography results, and neurohormonal factors between these two groups.

Results

In the NB group, a history of open-heart surgery (OHS) was more frequent (71% vs. 22%, p < 0.0001) and hypertension was less frequent (p = 0.0005). Left atrial diameter (LAd) was higher (p = 0.0026), while interventricular septal thickness, posterior wall thickness, relative wall thickness, left ventricular mass index were lower (p = 0.0005, p = 0.0225, p = 0.0114, p = 0.0051, respectively) in the NB group. In patients with HFNEF, a history of OHS remained an independent predictor of BNP level (< 100 pg/ml) after adjustment for hypertension, age, LAd, and interventricular septal thickness (odds ratio 3.6, p = 0.0252).

Conclusion

We found associations between acute HFNEF with less elevated BNP and a history of OHS. In a patient suspected of HFNEF, a history of OHS is considered diagnostic evidence of presence of diastolic heart failure when plasma levels of BNP are less elevated.     

Molecular assessment of c-H-ras p21 expression in Helicobacter pylori-mediated gastric carcinogenesis

Helicobacter pylori (H. pylori) infection plays a significant role in causing gastric cancer; the exact molecular mechanisms of gastric carcinogenesis have not yet been fully determined. Therefore, this study was planned to examine the role of c-H-ras p21 expression in H. pylori infection at different stages of disease progression from precursor lesions to gastric carcinoma. This study was carried out in 200 patients, consisting of normal gastric mucosa (n = 20), mucosa with chronic gastritis (n = 63), intestinal metaplasia (n = 20), dysplasia (n = 11), and gastric adenocarcinoma (n = 86), in which the H. pylori status have been analysed. The expression of c-H-ras p21 was studied at mRNA as well as protein level using RT-PCR and western blotting, respectively. The localization of c-H-ras p21 was also studied semiquantitatively by immunohistochemistry. The RT-PCR and western blotting results of c-H-ras p21 mRNA and protein expressions were significantly increased in chronic gastritis, intestinal metaplasia, dysplasia, and gastric adenocarcinoma patients, respectively. Immunohistochemical study also showed the increased expression of c-H-ras p21 in the similar way. Overexpression of c-H-ras p21 might be due to H-ras mutation at codon 12 of ras gene family in H. pylori infection. The rate of expression of ras p21 was higher in the H. pylori-infected precursor lesions, chronic gastritis 49/56 (87.5%), intestinal metaplasia 16/17 (94%), and dysplasia 9/11(82%) whereas in the case of H. pylori negative cases these groups, show 12.5, 5.9, and 18.2%, respectively. The data suggested that H. pylori infection may increase the expression of c-H-ras p21 early in the process of gastric carcinogenesis.     

Proteomic changes at 8 weeks after infection are associated with chronic liver pathology in experimental schistosomiasis

Chronic Schistosoma mansoni infection can present as a moderate or severe disease, termed intestinal or hepatosplenic schistosomiasis, respectively. Similarly, either moderate splenomegaly or hypersplenomegaly syndrome develops in CBA/J mice by 20 weeks of infection and is similar to intestinal or hepatosplenic schistosomiasis respectively. Using this mouse model and two-dimensional differential in gel electrophoresis, the liver proteomic signatures of uninfected mice and mice infected for 6, 8, 12, or 20 weeks were compared, and significant protein spots identified using mass spectrometry. We found the greatest number of changes at 12 weeks suggesting that this period represents the peak time of change. Pathway analysis identified specific proteins and pathways that correlated to the pathological changes indicative of severe disease, and these pathways were involved as early as 8 weeks after infection. These findings provide insight into the development of severe liver pathology in schistosomiasis and may aid in developing biomarkers for hepatosplenic schistosomiasis.     

Diagnostic value of dengue virus-specific IgA and IgM serum antibody detection

The diagnostic value of dengue virus (DV)-specific immunoglobulin A (IgA) serum antibody detection, by an indirect immunofluorescence assay (IFA) was evaluated. For this study, the kinetics of DV-specific IgA serum antibodies was analysed in two experimentally immunised macaques, paired samples from 35 patients suspected of a primary or secondary DV infection, paired sera from patients with high levels of IgA specific antibodies against influenza virus (n = 15), sera from patients with other viral infections (n = 40) and healthy blood donors (n = 10), which served as controls. The presence of DV-specific IgA serum antibodies in humans and in monkeys was compared with that of DV-specific IgM demonstrated in a capture enzyme-linked immunosorbent assay (ELISA). The development of DV-specific IgA and IgM antibodies in macaques proved to be similar to that observed in humans with a DV infection. In sera obtained from suspected primary DV patients during the acute phase and convalescent phase, DV-specific IgA was detected in 1/6 (17%) and 6/6 (100%), whereas IgM was detected in 4/6 (67%) and 5/6 (83%), respectively. In sera from suspected secondary DV patients during the acute phase and convalescent phase, DV-specific IgA was detected in 18/29 (62%) and 28/29 (97%), whereas IgM was detected in 20/29 (69%) and 28/29 (97%), respectively. The control group consisted of five paired serum samples from yellow fever vaccinated individuals and a patient with acute tick-borne encephalitis, 15 paired serum samples from patients with high levels of IgA antibodies specific for influenza virus and 40 serum samples from patients with specific IgM antibodies against other viruses. Ten serum samples from healthy blood donors were included. Among the control serum samples, in one patient, both DV-specific IgA and IgM antibodies were present, and in three sera DV-specific IgM antibodies could be demonstrated. These data suggest that detection of DV-specific IgA serum antibodies by IFA may have additional value for the diagnosis of DV infection.     

sTNFR-II and sICAM-1 are associated with acute disease and hepatic inflammation in schistosomiasis japonica

Soluble intracellular adhesive molecule 1 (sICAM-1) and tumour necrosis factor receptors I (TNFR-1) and II (TNFR-II) have been shown to be associated with numerous liver disorders. Shedding of these membrane proteins can be triggered by the Th1 cytokines, TNF-alpha and IFN-gamma, which are associated with susceptibility or resistance to hepatic schistosomiasis, respectively. Further, TNF-alpha receptors and sICAM-1 have been implicated in periportal fibrosis in advanced human schistosomiasis mansoni and correlate with schistosome granuloma formation in the murine model. We measured serum levels of sICAM-1, TNFR-I and TNFR-II in Chinese patients with different clinically defined stages of schistosomiasis japonica and controls; these included 35 patients with acute schistosomiasis, 45 patients with chronic schistosome infections, 34 advanced patients with evidence of severe morbidity and 20 patients with no known history of exposure to infection. Markedly elevated levels of soluble TNFRs (sTNFRs) and sICAM-1 were observed in the acute and advanced patients compared with the chronic and control groups. Mean sTNFR-II levels were significantly higher in acute patients compared with advanced (P<0.00001) and chronic patients (P<0.00001) and showed the strongest association of the markers with acute disease (odds ratio (OR)=1.099). sTNFR-II and sICAM-1 levels both correlated with infection intensity and there were significant positive correlations observed between eosinophil count and infection intensity (P=0.0072) and sICAM-1 (P=0.0014). Although there were significantly higher levels of antigen-specific IgG4 and total IgG in infected individuals compared with controls, none correlated with infection intensity. Further, no differences in IgG4 and total IgG levels were observed between the acute and chronic groups. The results suggest sTNFRs and sICAM-1 are associated with liver inflammation and disease progression. Measurement of sTNFR-II and sICAM-1 levels in serum could serve as additional markers for the diagnosis of acute stage disease and the monitoring of hepatic inflammation in human schistosomiasis japonica.     

Plasma albumin cysteinylation is regulated by cystathionine beta-synthase

High homocysteine (Hcy) levels are a well-known independent risk factor for endothelial damage in atherosclerosis. We examined whether a rat intestinal model of ischemia-reperfusion was associated with high Hcy and with the modification of plasma albumin into cysteinylated species (CysAlb). The three treatment groups were as follows: midline abdominal incision (group A, n=10), followed by ligation of the superior mesenteric artery for a period of 2h (group B, n=3), and followed by reperfusion for 1h (group C, n=10). Hcy levels were 2.5-fold higher in group C than group A (p<0.05). 100% and 73.44+/-0.04% of Alb were modified into Cys species in groups C and B, respectively, compared to 51.2% in group A. A cystathionine beta-synthase (CBS) deficient mouse model, known to have high plasma Hcy levels, was also used to determine the extent of CysAlb. Hcy levels, %CysAlb, and %HcyAlb were 180.1+/-45.7 microM, 0%, and 23.4+/-4.4% in CBS deficient mice, while in control mice, those values were 5.7+/-1.8 microM, 24.2+/-4.1%, and 0%, respectively (p<0.05). High CysAlb and Hcy levels were observed in a rat model of bowel ischemia/reperfusion while high HcyAlb and Hcy levels with no CysAlb were observed in the CBS deficient mice. CysAlb may serve as a biomarker for the severity of gut ischemia, and high Hcy may explain endothelial damage associated with this model. Additionally, active CBS is essential for the formation of CysAlb.     

Morbidity associated with Schistosoma mansoni infection in north-eastern Democratic Republic of the Congo

BackgroundReducing morbidity is the main target of schistosomiasis control efforts, yet only rarely do control programmes assess morbidity linked to Schistosoma sp. infection. In the Democratic Republic of Congo (DRC), and particularly in north-eastern Ituri Province, little is known about morbidity associated with Schistosoma mansoni infection. For this reason, we aimed to assess intestinal and hepatosplenic morbidity associated with S. mansoni infection in Ituri Province.Methods/Principal findingsIn 2017, we conducted a cross-sectional study in 13 villages in Ituri Province, DRC. S. mansoni infection was assessed with a Kato-Katz stool test (2 smears) and a point-of-care circulating cathodic antigen (POC-CCA) urine test. A questionnaire was used to obtain demographic data and information about experienced intestinal morbidity. Each participant underwent an abdominal ultrasonography examination to diagnose hepatosplenic morbidity. Of the 586 study participants, 76.6% tested positive for S. mansoni. Intestinal morbidity reported in the two preceding weeks was very frequent, and included abdominal pain (52.7%), diarrhoea (23.4%) and blood in the stool (21.5%). Hepatosplenic morbidity consisted of abnormal liver parenchyma patterns (42.8%), hepatomegaly (26.5%) and splenomegaly (25.3%). Liver pathology (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.06–1.37, p = 0.005) was positively and significantly associated with S. mansoni infection. Hepatomegaly (aOR 1.52, 95% CI 0.99–2.32, p = 0.053) and splenomegaly (aOR 1.12, 95% CI 0.73–1.72, p = 0.619) were positively but not significantly associated with S. mansoni infection at the individual level. At the village level, S. mansoni prevalence was positively associated with the prevalence of hepatomegaly and splenomegaly. High-intensity S. mansoni infections were associated with diarrhoea, blood in the stool, hepatomegaly, splenomegaly, and liver parenchyma (C, D, E and F pathology patterns). Four study participants were diagnosed with ascites and five reported hematemesis.Conclusions/SignificanceOur study documents a high burden of intestinal and hepatosplenic morbidity associated with S. mansoni infection status in Ituri Province. The findings call for targeted interventions to address both S. mansoni infection and related morbidity.     

Involvement of PSMD10, CDK4, and Tumor Suppressors in Development of Intrahepatic Cholangiocarcinoma of Syrian Golden Hamsters Induced by Clonorchis sinensis and N-Nitrosodimethylamine

Background

Clonorchis sinensis is a group-I bio-carcinogen for cholangiocarcinoma (CCA). Although the epidemiological evidence links clonorchiasis and CCA, the underlying molecular mechanism involved in this process is poorly understood. In the present study, we investigated expression of oncogenes and tumor suppressors, including PSMD10, CDK4, p53 and RB in C. sinensis induced hamster CCA model.

Methods

Different histochemical/immunohistochemical techniques were performed to detect CCA in 4 groups of hamsters: uninfected control (Ctrl.), infected with C. sinensis (Cs), ingested N-nitrosodimethylamine (NDMA), and both Cs infected and NDMA introduced (Cs+NDMA). The liver tissues from all groups were analyzed for gene/protein expressions by quantitative PCR (qPCR) and western blotting.

Principal Findings

CCA was observed in all hamsters of Cs+NDMA group with well, moderate, and poorly differentiated types measured in 21.8% ± 1.5%, 13.3% ± 1.3%, and 10.8% ± 1.3% of total tissue section areas respectively. All CCA differentiations progressed in a time dependent manner, starting from the 8^th week of infection. CCA stroma was characterized with increased collagen type I, mucin, and proliferative cell nuclear antigen (PCNA). The qPCR analysis showed PSMD10, CDK4 and p16INK4 were over-expressed, whereas p53 was under-expressed in the Cs+NDMA group. We observed no change in RB1 at mRNA level but found significant down-regulation of RB protein. The apoptosis related genes, BAX and caspase 9 were found downregulated in the CCA tissue. Gene/protein expressions were matched well with the pathological changes of different groups except the NDMA group. Though the hamsters in the NDMA group showed no marked pathological lesions, we observed over-expression of Akt/PKB and p53 genes proposing molecular interplay in this group which might be related to the CCA initiation in this animal model.

Conclusions/Significance

The present findings suggest that oncogenes, PSMD10 and CDK4, and tumor suppressors, p53 and RB, are involved in the carcinogenesis process of C. sinensis induced CCA in hamsters.     

Humoral recall responses in HIV infection. Levels, specificity, and affinity of antigen-specific IgG

To evaluate the integrity of humoral immunologic memory among persons with HIV infection, we measured the levels, specificity, and functional affinity of circulating antibodies to vaccine-related recall Ag, tetanus (TT) and diphtheria toxoids (DT), and to naturally acquired measles virus, in sera from 17 HIV-seronegative control subjects, 17 asymptomatic HIV-seropositive patients, and 10 patients with AIDS. Preimmunization levels of TT- and measles-specific IgG were similar in all groups, although DT-specific IgG was lower in AIDS patients. Four wk after immunization with TT3 and DT, all groups showed significantly increased specific antibody levels (p less than 0.02). The asymptomatic HIV+ patients and control subjects achieved similar peak serum levels of TT-specific IgG (102 +/- 32 and 169 +/- 36 micrograms/ml, respectively). In contrast, the AIDS patients had lower peak values of both TT- and DT- specific IgG (p less than 0.05). Peak levels correlated directly with the number of CD4+ T cells (p less than 0.05). However, 80 to 100% of all participants tested, independent of HIV status, showed higher levels of TT- and DT-specific IgG 6 mo after immunization compared with preimmunization levels. The antitoxoid antibodies were specific as they did not cross-react with other Ag in competitive inhibition experiments. In addition, all groups exhibited antibodies to TT and DT both pre- and postimmunization of equivalent functional affinity (avidity) (Kd = 10(-10)-10(-11) mol/liter). We conclude that, in contrast to the profoundly depressed humoral responses to new Ag, persons with asymptomatic HIV infection retain humoral immunity to certain recall Ag. These levels of specific IgG to three recall Ag are not proportional to elevated levels of total serum IgG in HIV-infected patients. In addition, many patients with HIV respond to challenge with recall Ag by producing significant amounts of high affinity IgG that may persist over time.     

Efficacy of moxifloxacin (Avelox) in prophylaxis of infection in patients with profound neutropenia]

Comparative efficacy of moxifloxacin and ciprofloxacin as prophylactics of infection in cancer patients with severe neutropenia after the chemotherapy was studied. The study included 40 patients with malignant lymphomas and solid tumore who received 52 courses of the aggressive chemotherapy. Twenty four patients (30 courses) received oral moxifloxacin in a dose of 400 mg once a day from the first day of the neutrophil count decrease below 1.0 x 10(9)/l until its recovery to > 1.0 x 10(9)/l or when the signs of infection appeared. In the control group 16 patients (22 courses) received oral ciprofloxacin in a dose of 500 mg twice a day. The patients in both the groups were compatible by the diagnosis, age and neutropenia duration. The median of the days of the febrile neutropenia duration in the patients prophylactically treated with moxifloxacin was statistically lower (2.1 vs 3.6 in the control group, p < 0.05). The incidence of febrile neutropenia in the moxifloxacin group was significantly lower than that in the control group (73 and 100% respectively, p = 0.01). The incidence of bacteriologically confirmed infection in the moxifloxacin group was also lower (6% vs 27.2%, p = 0.04). Therefore, moxifloxacin proved to be a more efficient agent vs ciprofloxacin (standard prophylactic) in prevention of febrile neutropenia and neutropenic infection in cancer patients, which is likely due to its higher activity against grampositive organisms.     

Testing for antibodies to tick-borne encephalitis virus using blood dried on filter paper

Possibility to use blood dried on filter paper for serological testing on antibodies to tick-borne encephalitis (TBE). Sensitivity and specificity of specific IgM detection in dry stains of blood by lanthanide fluorescence immunoassay was 94.9% (86.9-100%) and 97.5% (94-100%) respectively, compared with results obtained in tests of sera. Agreement in positive and negative results of tests for IgM against TBE in 562 serum samples and dry blood stains was 95.3%. During analysis of both types of biomaterial high degree of correlation was observed between intensity of fluorescence when testing for both IgM (r=0.86700; p=0.05; n=562), and IgG (r=0.83883; p=0.05; n=337) toTBE virus. Use of this mildly invasive technique of blood draw is reasonable during conduction of large-scale population studies for seroepidemiologic monitoring, investigation of disease outbreaks, control of effectiveness of vaccination against TBE, assessing of level of specific immunity in population of endemic regions, control of treatment, and serologic diagnostics of acute TBE in hospitalized patients, in which blood draw is difficult to perform.     

Human papillomavirus genotypes and the p53 codon 72 polymorphism in cervical cancer of Northeastern Thailand

Human papillomavirus (HPV) infection including sub-strain identification was studied in patients with squamous cell cervical cancer (SCCA) in Northeastern Thailand. Subjects were 90 cases of SCCA and 100 healthy controls. Prevalence of high-risk group of HPV infection in the controls and the SCCA patients were 13.0% and 86.7%, respectively. The HPV infection significantly increased the risk for cervical cancer 43.5-fold (95% confidential interval: 17.5-110.6; P <0.00001). Among HPV carrier patients with SCCA (n = 78), HPV-16 was also prominent (70.5%) followed by HPV-18 (23.1%). There was no statistical difference in the subtype distribution between the SCCA and the control groups. There was no significant association between genotype distribution of the p53 codon 72 polymorphism and HPV infection. HPV infection was confirmed as a critical risk factor for cervical cancer development in Northeast Thailand. Since polymorphism of the p53 itself as well as in combination with HPV infection may not be a genetic risk for cervical cancer, much attention should be paid to other risk factors such as sexual behavior and smoking.     

Lymphocyte DNA damage in patients with acute coronary syndrome and its relationship with severity of acute coronary syndrome

OBJECTIVE: The aim of this study was to investigate the association between lymphocyte DNA damage and acute coronary syndromes (ACS). METHODS: The study population contained 53 patients with ACS, 48 patients with stable angina and 35 voluntary healty subjects. DNA damage was assessed by alkaline comed assay in peripheral lymphocyte and plasma levels of total antioxidant capacity (TAC) were determined using a novel automated measurement method. RESULTS: In ACS patients, DNA damage was significantly higher than in patients with stable angina and control subjects (144+/-52 AU, 116+/-37, 68+/-34 AU; for three p<0.001, respectively). The TAC levels in patients with ACS were lower than the other groups (1.24+/-0.31 mmol Trolox equiv./l, 1.46+/-0.29 mmol Trolox equiv./l, p<0.05, respectively). DNA damage values in patients with acute miyocardial infarction were significantly higher than in patients with unstable angina (159.8+/-53.0 AU versus 131.8+/-48.4 AU; p<0.05, respectively). Lymphocyte DNA damage values in patients with ACS showed positive correlation with d-dimer (r=0.880, p<0.001) troponin I (r=538, p<0.001) and C-reactive protein (r=0.544, p<0.001) and negative correlation with TAC (r=-0.346, p=0.011). In multiple linear regression analysis, TAC (beta=-0.213, p=0.001) and d-dimer (beta=0.697, p<0.001) were independent predictors of DNA damage in patients with ACS. CONCLUSIONS:These findings indicate that lymphocyte DNA damage level increases in patients with ACS. Elevated DNA damage may be related with plaque instability and be useful for the identification of patients with acute coronary syndromes.