A prophylactic and therapeutic AIDS vaccine containing as a component the innocuous Tat Toxoid

Extracellular Tat can act as a viral toxin on uninfected cells of different tissues, including the CNS and the immune system, thus in order to immunize humans against Tat we have prepared a biologically inactivated but immunogenic Tat (Tat Toxoid). Tat Toxoid is not toxic in mice even at high doses. It triggers high levels of specific Tat Abs in the mouse and rabbit. Furthermore, in humans Tat Toxoid immunization was safe and induced in seronegatives persistent high levels of Tat Abs and in immunodeficient patients a significant rise of these specific Abs. Facing acute HIV-1 infection, the presence of high level of circulating Tat Abs promoted by Tat Toxoid vaccine should prevent Tatinduced immunosuppression and allow anti-HIV-1 cellular response to develop. As a consequence, early release of β-chemokines could enhance host resistance towards HIV-1, and, in infected people, inhibit viral replication and evolution towards AIDS.     

Low plasma DHEA-S increases mortality risk among male hemodialysis patients

Objective

The incidence of chronic kidney disease (CKD) is on the rise. CKD patients are at high risk of cardiovascular (CVD) and all-cause mortality. CKD patients have several endocrine disorders, including low levels of dehydroepiandrosterone sulfate (DHEA-S). In the general population, low levels of DHEA-S are associated with high CVD and all-cause mortality. The aim of this study was to analyze the prognostic value of plasma DHEA-S on the survival of CKD patients on hemodialysis.

Method

This was a single-center prospective cohort study on two hundred CKD patients on hemodialysis, which assessed the prognostic value of plasma DHEA-S on their survival.

Result

We found that plasma DHEA-S levels were negatively associated with age, and positively associated with dialysis duration and plasma creatinine, albumin, and phosphate levels in hemodialysis men. Elderly patients with co-morbidities (i.e. diabetes mellitus, congestive heart failure, and chronic obstructive pulmonary disease), poorer fluid control which was evaluated by higher cardiothoracic ratio, and low plasma creatinine and albumin levels seemed to have poor prognosis in hemodialysis men. Furthermore, low plasma DHEA-S levels were significantly associated with CVD-related [hazard ratio (HR) = 3.877; P = 0.021], non-CVD-related (HR = 3.522; P = 0.016), and all-cause mortality (HR = 3.667; P = 0.001) in hemodialysis men. But low plasma DHEA-S levels were not significantly associated with CVD-related, non-CVD-related, and all-cause mortality in hemodialysis women. Multivariate Cox regression analysis suggested that low plasma DHEA-S levels are significantly and independently associated with all-cause mortality in hemodialysis men (HR = 2.933; P = 0.033).

Conclusion

The study suggested that low plasma DHEA-S was independently and significantly associated with all-cause mortality in CKD hemodialysis men.     

Clinical and Virological Course of Chronic Hepatitis B Virus Infection With Hepatitis C and D Virus Markers

Objective : Hepatitis B, C, and delta virus (HBV, HCV, HDV) share similar transmission routes; thus, dual or triple infections may occur and even persist in the same patient. However, little is known about the presentations and course of chronic HBV infection with HCV and HDV markers, which this study examined. Methods : Antibodies against HCV (anti-HCV) and HDV (anti-HDV) were assayed as appropriate in patients with HBV infection. The clinical, pathological, and virological presentations as well as the course of the disease in patients with HBV/HDV/HCV triple infection markers were then reviewed. Results : A total of 60 patients, 51 men and nine women, age 19–67 yr (mean 45.9 ± 1.6 yr) were identified. Of these 60 patients, five (8.3%) were HBeAg positive and 10 (16.7%) cirrhotic at entry, 30 (50%) presented with acute superinfection (HCV or HDV, or both) and the remaining 30 presented with chronic liver disease. On presentation, 16 (53.3%) of the 30 patients with acute superinfection showed hepatic decompensation and eight (26.7%) died. In contrast, only one of the patients with "chronic liver disease" presented with hepatic decompensation. Of the 42 patients followed up for 1–15 (mean, 4.7 ± 0.6) yr, 45.2% showed remission and 19% showed HBsAg seroclearance, whereas 12.5% of the 32 noncirrhotics developed cirrhosis and three of the nine cirrhotics became decompensated. At the end of follow-up, 29 patients (69.9%) were still seropositive for HCV-RNA but only nine (22.5%) were seropositive for HDV-RNA and five (12.5%) were seropositive for HBV-DNA. Conclusions : These results suggest that infection with HBV, HCV, and HDV triple markers is a severe disease in acute superinfection stage but that the course is relatively benign, slowly progressive, and usually dominated by HCV.     

Hypermethylation of the CDKN2/p16 promoter during neoplastic progression in Barrett's esophagus

Background & Aims: Inactivation of the CDKN2/p16^INK4A tumor-suppressor gene is one of the most frequent genetic alterations in human malignancies. In esophageal adenocarcinomas, mutations of the p16 gene or homozygous deletions of the gene locus 9p21 are rare. This study investigated whether p16 promoter hypermethylation is an alternative mechanism for p16 gene inactivation during neoplastic progression in Barrett's esophagus. Methods: A methylation-specific polymerase chain reaction protocol was applied. A total of 95 specimens from 14 patients with Barrett's esophagus were analyzed longitudinally. The p16 promoter status was compared with histomorphological findings. Results: p16 promoter hypermethylation was detected in 9 of the 10 patients who had displayed dysplasia at some time during surveillance, whereas none of the patients who had not displayed dysplasia during surveillance had p16 promoter hypermethylation. p16 promoter hypermethylation was detected in 3% (2 of 67) of the samples without dysplasia, 60% (3 of 5) of the samples with lesions indefinite for dysplasia, 55.6% (10 of 18) of the specimens with low-grade dysplasia, and 75% (3 of 4) of the specimens with high-grade dysplasia. Conclusions: These data suggest that p16 promoter hypermethylation is a common mechanism of p16 gene inactivation during neoplastic progression in Barrett's esophagus.GASTROENTEROLOGY 1998;115:1381-1386     

The trend of hypertension and its relationship to the weight status among Taiwanese young adolescents

This study evaluates prevalence of hypertension in 1996 and 2006, and examines the relationship between hypertension and weight of Taiwanese young adolescents. Two cross-sectional surveys, administered in 1996 and 2006, to junior-high school in Taipei were included. Anthropometric and blood pressure were measured using standard methods, and structured questionnaire was used to collect personal history and lifestyle characteristics. Overweight and obesity are defined based on Taiwan's Department of Health criteria and bases pre-hypertension and hypertension on the 90th and 95th percentile distribution of blood pressure of the population of both surveys. The prevalence of pre-hypertension in Taiwan between 1996 and 2006 increased from 12.0 to 14.4% for boys and decreased from 9.5 to 9.4% for girls. Hypertension increased from 22.8-29.7% and 12.5-20.7% for both boys and girls, respectively. In 1996, compared with normal young adolescents, the risk of hypertension for overweight was 1.8 times higher for boys and 3.4 times for girls. However, the risk of hypertension for overweight in 2006 was 1.7 times higher for boys and 1.5 times higher for girls compared with normal. Every unit increment of body mass index and waist circumference was associated with 17-27% and 6-11% risk of hypertension in both genders in 1996, and was associated with 9-13% and 4% risk of hypertension among young adolescents in 2006, respectively. The prevalence of hypertension has increased significantly in young adolescents, especially for overweight. It is necessary to enrol young adolescents in weight management programs to prevent hypertension-related co-morbidities.     

Predictors of the outcomes of acute-on-chronic hepatitis B liver failure

AIM:To identify the risk factors in predicting the outcome of acute-on-chronic hepatitis B liver failure patients.METHODS:We retrospectively divided 113 patients with acute-on-chronic liver failure-hepatitis B virus(ACLF-HBV) and without concurrent hepatitis C or D virus infection and hepatocellular carcinoma into two groups according to their outcomes after anti-HBV therapy.Their demographic,clinical,and biochemical data on the day of diagnosis and after the first week of treatment were analyzed using the Mann-Whitney U test,Fisher's exact test,and a multiple logistic regression analysis.RESULTS:The study included 113 patients(87 men and 26 women) with a mean age of 49.84 years.Fiftytwo patients survived,and 61 patients died.Liver failure(85.2%),sepsis(34.4%),and multiple organ failure(39.3%) were the main causes of death.Multivariate analyses showed that Acute Physiology and Chronic Health Evaluation(APACHE) Ⅱ scores ≥ 12 [odds ratio(OR) = 7.160,95% CI:2.834-18.092,P 0.001] and positive blood culture(OR = 13.520,95% CI:2.740-66.721,P = 0.001) on the day of diagnosis and model for end-stage liver disease(MELD) scores ≥ 28(OR = 8.182,95% CI:1.884-35.527,P = 0.005) after the first week of treatment were independent predictors of mortality.CONCLUSION:APACHE Ⅱ scores on the day of diagnosis and MELD scores after the first week of anti-HBV therapy are feasible predictors of outcome in ACLFHBV patients.     

Thyroid autoantibodies and dysfunction do not impact the treatment efficacy of peginterferon and ribavirin combination therapy in chronic hepatitis C

Aims

Thyroid disorders, such as the emergence of thyroid autoantibodies (TAs) and thyroid dysfunction (TD), are not uncommon in chronic hepatitis C (CHC) patients. The study aimed to investigate the impact of TAs and dysfunction on the treatment response to pegylated interferon-?? plus ribavirin (PegIFN/RBV) combination therapy in CHC patients. The association between interleukin-28B (IL-28B) genetic variants and occurrence of TAs and dysfunction was also analyzed.

Methods

A total of 449 treatment-naive Taiwanese CHC patients with euthyroid status were consecutively enrolled. They received PegIFN/RBV combination therapy with current recommendation. TAs, TD, and IL-28B genetic variants were measured before treatment. Monitoring of TD was done at 3-month intervals during treatment, at end of treatment, and at end of follow-up (EOF).

Results

The development of TAs was detected in 42 (9.4%) patients before treatment, and the incidence of TD during or at EOF was 20%. Of 287 patients with IL-28B rs8099917 TT genotype, 29 (10.1%) had TAs before treatment, whereas the patients with other genotypes did not have TAs (P?=?0.04). There was no significant difference of TD incidence during treatment or at EOF between the patients with different IL-28B genotypes. There was also no significant difference of sustained virologic response according to the presence of TAs, TD, or different manifestations of TD.

Conclusion

Taiwanese CHC patients with rs8099917 TT genotype had a higher incidence of TAs. The development of TAs and TD did not impact the treatment efficacy of PegIFN/RBV combination therapy.     

Long-term outcomes following neoadjuvant chemoradiotherapy in patients with clinical T2N0 esophageal squamous cell carcinoma

The optimal treatment for patients with local esophageal cancer (cT2N0 disease) has not yet been defined. We sought to determine whether neoadjuvant chemoradiotherapy (CRT) can improve prognosis compared with direct esophagectomy in this patient group. Between 1994 and 2005, patients with cT2N0 esophageal squamous cell carcinoma who underwent either neoadjuvant CRT or surgery as first-line treatment were retrospectively reviewed. We collected information on their demographic characteristics, staging modality, clinical and pathological stages, perioperative course, and survival. The study endpoints included tumor recurrence, disease-specific survival (DSS), and overall survival rate. Of the 71 eligible patients, 14 received an esophagectomy first, whereas the remaining 57 received neoadjuvant CRT first. Despite the high pathological complete response (pCR) rate of 37% after neoadjuvant CRT, routine neoadjuvant CRT did not translate into better survival compared to direct surgery (5-year DSS: 39% vs. 68%, P= 0.17). The dramatic survival difference between pCR and non-pCR patients (5-year DSS: 85% vs. 4%, P < 0.001) accounts for these unsatisfactory results. In our series, the administration of neoadjuvant CRT to patients with clinical stage T2N0 esophageal squamous cell carcinoma did not significantly improve outcomes compared with direct esophagectomy.     

Continuous apex to left ventricle blood flow pattern in hypertrophic cardiomyopathy with apical aneurysm and midventricular obstruction

A 42-year-old female presented with chest pain, noted to have systolic and diastolic murmurs on physical examination and left ventricular hypertrophy on the electrocardiogram. Echocardiography with contrast enhancement revealed hypertrophic cardiomyopathy (HCM) with apical aneurysm and mid left ventricular cavity obstruction. Doppler interrogation showed continuous systolic and diastolic flow from the apex to left ventricle (LV) with a transient deceleration giving rise to a notched pattern. Myocardial ischemia of the apex was demonstrated on adenosine nuclear scintigraphy without epicardial coronary obstruction on angiography. This case demonstrates a novel Doppler pattern with continuous apex to LV flow in HCM in the setting of apical ischemia that may account for the formation of the aneurysm.