Volume 120  ·   Issue 01  ·  2007

Respiratory syncytial virus (RSV) is a leading cause of epidemic respiratory tract illness in children. Severe RSV infections involving the lower respiratory tract are primarily seen in young children with naive immune systems and/or genetic predispositions. However, RSV was not recognized as a potentially serious problem in older adults until the 1970s, when outbreaks of the virus infection occurred in long-term care facilities。

Abstract：Background The cellular plasma membrane represents a natural barrier to many exogenous molecules including magnetic resonance (MR) contrast agent. Cell penetrating peptide (CPP) is used to internalize proteins, peptides, and radionuclide. This study was undertaken to assess the value of a new intracellular MR contrast medium, CPP labeled diethylenetriamine pentaacetic acid gadolinium (Gd-DTPA) in molecular imaging in vitro. Methods Fluorescein-5-isothiocyanate (FITC) and Gd-DTPA respectively labeled with CPP (FITC-CPP, Gd-DTPA-CPP) were synthesized by the solid-phase method. Human hepatic cancer cell line-HepG2 was respectively stained by FITC-CPP and FITC to observe the uptake and intracellular distribution. HepG2 was respectively incubated with 100 nmol/ml Gd-DTPA-CPP for 0, 10, 30, 60 minutes, and imaged by MR for studying the relationship between the incubation time and T1WI signal. The cytotoxicity to NIH3T3 fibroblasts cells was measured by 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide reduction assay (MTT). Results The molecular weights of CPP labeled imaging agents, which were determined by MALDI mass spectrometry (FITC-CPP MW=2163.34, Gd-DTPA-CPP MW=2285.99), were similar to the calculated molecular weights. Confocal microscopy suggested HepG2 translocated FITC-CPP in cytoplasm and nucleus independent with the incubation temperature. MR images showed HepG2 uptaken Gd-DTPA-CPP had a higher T1 weighted imaging (T1WI) signal, and that the T1WI signal intensity was increasing in a time-dependent manner (r=0.972, P=0.001), while the signal intensity between the cells incubated by Gd-DTPA for 60 minutes and the controlled cells was not significantly different (P=0.225). By MTT, all concentrations from 50 nmol/ml to 200 nmol/ml had no significant (F=0.006, P=1.000) effect on cell viability of mouse NIH3T3 fibroblasts, compared with the control group. Conclusions The newly constructed CPP based on polyarginine can translocate cells by carrying FITC and MR contrast agent Gd-DTPA, and the intracellular concentrations are readily detectable by MR imaging, suggesting a new way for MR molecular imaging。

Abstract：Background Respiratory syncytial virus (RSV) is a common pathogen in the lower respiratory tract of infants and children. Recent studies have shown that in adults, especially in the elderly population who have relatively weak immunity, lower respiratory tract infection is not uncommon. RSV was detected in 22% hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (COPD), and the detection rate was only next to that of parvovirus and influenza virus respectively. Further studies revealed that lung infection of RSV could lead to inflammatory destruction and structural remodeling. This study was undertaken to examine the effect of infection with RSV on matrix metalloproteinase (MMPs) in mice, and to explore the role of RSV in the pathogenesis of pulmonary diseases. Methods Twenty BALB/c mice were divided randomly into an RSV infection group and a blank control group. The mice in the RSV infection group were given 100 μl liquid containing 106 PFU of RSV by intranasal instillation. Three days after the infection, the bronchoalveolar lavage fluid (BALF) was harvested and RT-PCR and Western blotting were used to detect MMP-9 and the expression of tissue inhibitors of matrix metalloproteinase (TIMP)-1 mRNA in lung tissues. Gelatin zymography was employed to detect the activities of MMP-9 and MMP-2 in BALF. Immunohistochemistry was used to determine the expressions of E-cadherin (E-cd) and proliferating cell nuclear antigen (PCNA) in the lung tissues. Results In the BALF of the mice infected with RSV, the activities of MMP-9 and MMP-2 were significantly increased (t=6.08, P＜0.01 and t=5.68, P＜0.01). The levels of mRNA and proteins of MMP-9 in the lung tissues of the mice infected with RSV were significantly elevated, and the mRNA and protein levels were significantly higher than those of the blank controls. Though the ratio of MMP-9/TIMP-1 mRNA in the lung tissues of the infected mice was not significantly different from that of the normal controls, the ratio of the MMP-9/TIMP-1 protein in the RSV infection group was significantly higher than that in the control group. Moreover, the number of cells with positive E-cd expression was decreased and the number of cells positive for PCNA was increased, with an enhanced expression. Conclusions In mice, infection with RSV can significantly increase the activities of MMP-9 and MMP-2, and conspicuously elevate the mRNA transcription of MMP-9. RSV infection can increase the activity of gelatinase while up-regulating its inhibitory factors but increase its protein ratio of MMP-9/TIMP-1 in lung tissues, thereby facilitating fibrosis after structural destruction of the airway. The resultant status might be an important factor causing chronic reconstruction of the airway。

Abstract：Background Laparoscopic splenectomy (LS) has been considered as the standard approach to remove a normal-sized spleen, but it is facing technical challenges when applied to splenomegaly. Hand-assisted laparoscopic technique was designed to facilitate the performance of difficult laparoscopic procedure. This study was aimed to evaluate the efficacy and superiority of hand-assisted laparoscopic splenectomy (HALS) for splenomegaly.Methods From November 1994 to January 2006, 36 patients with splenomegaly (final spleen weight ＞700 g) were treated with laparoscopic operations for splenectomy in our hospital. Conventional LS was performed in 16 patients (7men and 9 women, group 1) and HALS in the other 20 patients (12 men and 8 women, group 2). The patients' features,intraoperative details and the postoperative outcomes in the both groups were compared.Results The both groups were comparable in the terms of patient's age ((38±12) years vs (43±14)years, P＞0.05), the greatest splenic diameter ((24±5)cm vs (27±7)cm, P＞0.05), preoperative platelet count ((118±94)×109/L vs (97±81)×109/L,P＞0.05) and diagnosis. Compared with LS group, operation time ((195±71) minutes vs (141±64) minutes, P＜0.05) was shorter, intraoperative blood loss ((138±80)ml vs (86±45)ml, P＜0.05) and conversion rate (4/16 vs 0/20, P＜0.05) were lower, but hospital stay ((5.3±3.8) days vs (7.4±1.6) days, P＜0.05) was longer in HALS group. There was no significant difference in the aspects of intraoperative and postoperative complication rate (2/16 vs 0/20,P＞0.05) or recovery time of gastrointestinal function ((16.3±11.6) hours vs (18.7±8.1)hours, P＞0.05) between the two groups.Conclusions In the cases of splenomegaly, HALS significantly facilitates the surgical procedure and reduces the operational risk, while maintaining the advantages of conventional LS. HALS is more feasible and more effective than conventional LS for the removal of splenomegaly。

Abstract：Background Esophagogastric variceal bleeding caused by cirrhosis is a kind of emergent condition in the clinic. This study was conducted to explore the therapeutic effect and superiority of embolization of gastric fundus varices combined with endoscopic variceal ligation (EVL) of esophageal varices for the treatment of patients with esophagogastric variceal bleeding caused by cirrhosis.Methods Totally 172 patients were diagnosed by endoscopic examination within 24 hours of hospitalization with active gastric fundus variceal bleeding and grade Ⅱ above esophageal varices caused by cirrhosis. Other causes leading to upper digestive tract bleeding were excluded. Patients were randomly divided into a control group (n=82) and a therapy group (n=90) following a random number table method. For the former, embolization for gastric fundus varices was performed, then an EVL for esophageal varices was performed 2 months later. For the therapy group, embolization for gastric fundus varices and EVL for esophageal varices were performed at the same time.Results The rate of emergency hemostasis in the therapy group was 100.0%, higher than that in the control group (87.8%, P＜0.05). The rate of early rebleeding in the therapy group was 6.7% while the rate in the control group was 23.6% (P＜0.05). No complications related to treatment occurred in both groups.Conclusion Embolization for gastric fundus varices combined with EVL for esophageal varices is a safe and effective method for the treatment of patients with esophagogastric variceal bleeding caused by cirrhosis。

Abstract：Background The diagnosis of small bowel diseases remains relatively inefficient using traditional imaging techniques.Capsule endoscopy (CE) and double-balloon enteroscopy (DBE) are two novel methods of enteroscopy for examining the entire small bowel. The aim of this study was to evaluate the detection rate and diagnostic accuracy of CE and DBE in patients with suspected small bowel diseases and to investigate the clinical significance of combined use of these two novel modalities.Methods Two hundred and eighteen patients were evaluated for suspected small bowel disease, including 116 with obscure gastrointestinal bleeding and 102 with obscure abdominal pain or chronic diarrhea. One hundred and sixty-five out of these patients underwent CE first and 53 patients underwent DBE (under anesthesia with propofol) first. DBE was recommended after negative or equivocal evaluation on CE and vise versa. Introduction of the endoscope during DBE was either orally or anally and the patients were referred for a second procedure using the opposite route several days later when no abnormalities were found on the first procedure. The detection rates, diagnostic accuracy, tolerance and frequency of adverse events of these two modalities were then analyzed.Results Failure of the procedure was seen in one patient with CE and in two patients with DBE. Sixty-four DBE procedures were carried out in 51 patients; by the oral route in 34 cases, the anal route in 4 and both routes in 13 cases.The overall detection rate of small bowel diseases using CE (72.0%, 118/164) was superior to that with DBE (41.2%,21/51); χ2=16.1218, P＜0.0001. The diagnostic rate (51.8%, 85/164) was also higher than that with the latter procedure (39.2%, 20/51), but was not significantly different (χ2=2.4771, P＞0.05). Furthermore, the detection rate of small bowel diseases in patients with obscure gastrointestinal bleeding using CE (88.0%, 88/100) was superior to that of DBE (60.0%,9/15); χ2=7.7457, P=0.0054. Lesions were detected by DBE in 1 out of 4 patients in whom CE had a negative result.Suspected findings by CE were confirmed by DBE combined with biopsy in 12 out of 15 patients. On the other hand,small bowel lesions were identified by CE in all 3 patients after negative evaluations by DBE. There were no severe complications during or after either of the two procedures.Conclusions The detection rate of small bowel diseases by CE is very high. CE should be selected for the initial diagnosis in patients with suspected small bowel diseases, especially in patients with obscure gastrointestinal bleeding.DBE appears to be inferior to CE in the diagnosis of small bowel diseases. However, it was shown that abnormalities could still be identified by DBE in patients with normal images or used to confirm suspected findings from CE. DBE can also serve as a good complementary approach after an initial diagnostic imaging using CE。

Abstract：Background The RhoA/Rho kinase pathway may participate in the pathogenesis of hypoxia and monocrotaline induced pulmonary hypertension. This study tested whether RhoA/Rho kinase pathway is involved in the pathogenesis of high flow induced pulmonary hypertension in rats.Methods Male Wistar rats (4 weeks) were randomly divided into 4 shunt groups, 4 treated groups and 4 control groups.Shunt and treated groups underwent left common carotid artery/external jugular vein shunt operation. Control groups underwent sham operation. Treated groups received fasudil treatment and the others received same dose of saline. At weeks 1, 2, 4 and 8 of the study, right ventricular systolic pressure was measured and blood gases were analysed to calculate Qp/Qs. The weight ratio of right ventricle to left ventricle plus septum and the mean percentage of medial wall thickness in moderate sized pulmonary arteries were obtained. RhoA activity in pulmonary arteries was detected using Rho activity assay reagent. Rho kinase activity was quantified by the extent of MYPT1 phosphorylation with Western blot.Proliferating cells were evaluated using proliferating cell nuclear antigen immunohistological staining.Results Carotid artery/jugular vein shunt resulted in high pulmonary blood flow, both an acute and a chronic elevation of right ventricular systolic pressure, significant medial wall thickening characterized by smooth muscle cells proliferation,right ventricular hypertrophy and increased activation of RhoA and Rho kinase. Fasudil treatment lowered pulmonary artery systolic pressure, suppressed pulmonary artery smooth muscle cells proliferation, attenuated pulmonary artery medial wall thickening and inhibited right ventricular hypertrophy together with significant suppression of Rho kinase activity but not Rho activity.Conclusions Activated RhoA/Rho kinase pathway is associated with both the acute pulmonary vasoconstriction and the chronic pulmonary artery remodelling of high flow induced pulmonary hypertension. Fasudil treatment could improve pulmonary hypertension by inhibiting Rho kinase activity。

Abstract：Background Acute pulmonary thromboembolism (APE) causes right ventricular dysfunction (RVD) and cardiac troponin I (cTnI) elevation. Patients with RVD and cTnl elevation have a worse prognosis. Thus, early detection of RVD and cTnl elevation is beneficial for risk stratification. In this study, we assessed 14-day adverse clinical events and combined RVD on transthoracic echocardiography (TTE) with cTnl in risk stratification among a broad spectrum of APE patients.Methods The prospective multi-centre trial included 90 patients with confirmed APE from 12 collaborating hospitals.Acute RVD on TTE was diagnosed in the presence of at least 2 of the following: right ventricular dilatation (without hypertrophy), loss of inspiratory collapse of inferior vena cava (IVC), right ventricular (RV) hypokinesis, tricuspid regurgitant jet velocity ＞2.8 m/s. The study patients were divided into two groups according to clinical and echocardiographic findings at presentation: Group Ⅰ: 50 patients with RVD; Group Ⅱ: 40 patients without RVD.Results More than half of the patients (50/90, 55.6%) had RVD. Nearly one third (26/90, 28.9%) of patients had elevated cTnl at presentation and only 4.2% on the fourth day after initial therapy. A multiple Logistic regression model implied RVD, right and left ventricular end-diastolic diameter ratio (RVED/LVED), and cTnl independently predict an adverse 14-day clinical outcome (P＜0.01). Receiver operating characteristics (ROC) curves revealed that the cut-off values of RVED/LVED and cTnl yielding the highest discriminating power were 0.65 and 0.11 ng/ml, respectively.Furthermore, the incidence of an adverse 14-day clinical event in patients with RVD and elevated cTnl was greater (40.7%) than in patients with elevated cTnl or positive RVD alone (0% and 8.3%, respectively) (P＜0.001).Conclusions RVD, RVED/LVED, and cTnl are independent predictors of 14-day clinical outcomes. The patients with RVED/LVED greater than 0.65 and cTnl higher than 0.11 ng/ml at presentation possibly have adverse 14-day events.RVD combined with cTnl can identify a subgroup of APE patients with a much more guarded prognosis。

Abstract：Background Recent studies have suggested that susceptibility to chronic obstructive pulmonary disease (COPD)might be related to the length polymorphism of (GT)n repeat in the 5'-flanking region of heme oxygenase-1 (HOX-1) gene.However, there has been no research about the relationship between the polymorphism of HOX-1 gene and severity of COPD.Methods The polymorphism of HOX-1 gene in 452 patients with COPD from Han population in Southwest China was analysed by fragment analysis. The frequencies of the HOX-1 genotype were compared with the stage of COPD of each patient.Results The HOX-1 genotypes were classified into two groups: group Ⅰ were individuals with class L allele (the number of GT ≥32 repeats), and group Ⅱ were those without class L allele (the number of GT ＜32 repeats). The genotypic frequency of the HOX-1 group Ⅰ was significantly higher than group Ⅱ in the very severe COPD patients (36.8% vs 22.4%,P＜0.01, OR=2.0, 95% CI 1.3-3.1), while the genotypic frequency of the HOX-1 group Ⅱ was lower in the mild COPD (16.0% vs 26.0%, P=0.02, OR=0.5, 95% CI 0.3-0.9). However, in moderate and severe stages COPD, there were similar genotypic frequencies between HOX-1 group Ⅰ and group Ⅱ.Conclusions Genetic polymorphism in HOX-1 is associated with the severity of COPD in Southwest China. COPD patients with class L allele may be susceptible to develop very severe COPD. Conversely, the COPD patients without class L allele may be more easily stabilized on mild COPD。

Abstract：Background Waardenburg syndrome type Ⅰ (WS1) is an autosomal dominant disorder characterized by sensorineural hearing loss, pigmental abnormalities of the eye, hair and skin, and dystopia canthorum. The gene mainly responsible for WS1 is PAX3 which is involved in melanocytic development and survival. Mutations of PAX3 have been reported in familiar or sporadic patients with WS1 in several populations of the world except Chinese. In order to explore the genetic background of Chinese WS1 patients, a mutation screening of PAX3 gene was carried out in four WS1 pedigrees. Methods A questionnaire survey and comprehensive clinical examination were conducted in four Chinese pedigrees of WS1. Genomic DNA from each patient and their family members was extracted and exons of PAX3 were amplified by PCR. PCR fragments were ethanol-purified and sequenced in both directions on an Abl_Prism 3100 DNA sequencer with the BigDye Terminator Cycle Sequencing Ready Reaction Kit. The sequences were obtained and aligned to the wild type sequence of PAX3 with the GeneTool program. Results Two nonsense PAX3 mutations have been found in the study population. One is heterozygous for a novel nonsense mutation S209X. The other is heterozygous for a previously reported mutation in European population R223X. Both mutations create stop codons leading to truncation of the PAX3 protein. Conclusions This is the first demonstration of PAX3 mutations in Chinese WS1 patients and one of the few examples of an identical mutation of PAX3 occurred in different populations。

Myocardial protection (MP) is the key for cardiopulmonary bypass (CPB) heart surgery. MP during cardiac surgery (CS) aims to preserve myocardial function while providing a bloodless and motionless operating field. Strategies on how to attenuate or prevent post-ischemic myocardial dysfunction that occurs intra-operatively during CS have been discussed for more than half a century. In 1950, Bigelow et al1 first reported to decrease myocardial oxygen demand by means of hypothermia。

In recent years, the incidence of systematic severe infection in intensive care units (ICUs) has increased significantly. Sepsis is a complex, multifactorial syndrome that can develop into conditions of different severity, described as severe sepsis or septic shock.1 The immunology of severe sepsis and septic shock is poorly defined, despite many studies investigating the pathogenesis of this syndrome. With mortality rates of up to 50%,2, 3 greater understanding of the interactions between host and microbe is necessary to improve patient outcome。

Several studies have demonstrated that 30%-40% of cancer patients suffer from psychiatric problems such as depression, anxiety and adjustment disorders.1-3 The more positively the breast cancer patients rated their appraisal and tangible dimensions of social support, the lower value their mean cortisol level.4 Malignant melanoma patients who received 6-week structured intervention showed a lessening of emotional discomfort,augmentation of immune function and a decreased recurrence rate and mortality.5,6

The prevalence of coronary artery disease (CAD) in women increases with menopause. Results from the studies on the role of endogenous sex hormones on CAD in postmenopausal women are conflicting.1,2 The present study evaluated the relationship between endogenous sex hormones and extent of CAD in postmenopausal women and the associations of sex hormones with CAD risk factors。

Pseudomonas aeruginosa (P. aeruginosa) is one of the leading pathogens involved in nosocomial pneumonia. In addition, P. aeruginosa infection is associated with significant morbidity and mortality.1 A major problem in P. aeruginosa infection is that this organism exhibits natural and acquired resistance to many structurally and functionally diverse antibiotics。

Borderline personality disorder (BPD) is a serious Bpersonality disorder characterized by a pervasive pattern of disturbances in mood regulation, impulse control, self-image and interpersonal relationships.1 In the United States, the prevalence of BPD has been estimated at 1%-2% of the general population, 10% of psychiatric outpatients, and 20% of inpatients.2,3 According to the 4th text revision of diagnostic and statistical manual of mental disorders (DSM-Ⅳ-TR),1 about 75% of BPD patients are women. The BPD diagnosis has been associated with heightened risk (8.5% to 10.0% among BPD patients) for completed suicide, a rate almost 50times higher than in the general population.4

Acoustic neurinoma usually results in impairment of facial nerve and hearing, and rarely leads to subarachnoid hemorrhage (SAH). In 2002, we treated a patient with bilateral acoustic neurinomas presenting as SAH。