Therapeutic vaccination with papillomavirus E6 and E7 long peptides results in the control of both established virus-induced lesions and latently infected sites in a pre-clinical cottontail rabbit papillomavirus model

This study was performed to test the therapeutic efficacy of overlapping long E6 and E7 peptides, containing both CD4+ T-helper and CD8+ CTL epitopes, on CRPV-induced lesions, which is an appropriate pre-clinical model for HPV diseases, including recurrent respiratory papillomatosis (RRP). Therapeutic peptide vaccination was able to significantly control wart growth (p < 0.01) and abrogate latent CRPV infection (p = 0.0006) compared to controls. Vaccination was associated with a T(H)1 T cell response, as suggested by a strong DTH skin test, antigen-specific proliferation of PBMC and a minimal IgG antibody response. Thus, this study shows promise for treatment of RRP by vaccination with long peptides.     

Fatal aortic rupture presenting as chest pain in an adolescent. The role of echocardiography in occult cystic medial necrosis

An adolescent female with occult cystic medial necrosis died following spontaneous aortic rupture. A large saccular aortic aneurysm that had ruptured into the pericardial space was demonstrated by two-dimensional echocardiography and confirmed at surgery. Echocardiographic screening of the patient's family members revealed a 13-year-old brother with unsuspected aortic root dilatation. He is now being followed for possible progression of his disease. This case demonstrates the role of echocardiography in cystic medial necrosis. It can aid the acute management of patients with aortic dissection or aneurysm. It can also define patients with occult disease who require serial follow-up and genetic counseling.     

Serum hyaluronate as a non-invasive marker of hepatic fibrosis and inflammation in HBeAg-negative chronic hepatitis B

Background  

HBV infection is a serious global heath problem. It is crucial to monitor this disease more closely with a non-invasive marker in clinical trials. We aimed to evaluate the predictive value of serum hyaluronate for the presence of extensive liver fibrosis and inflammation.     

Off-pump coronary artery surgery for reducing mortality and morbidity: meta-analysis of randomized and observational studies

OBJECTIVES: The purpose of this study was to assess the effects of off-pump coronary bypass surgery (OPCAB) on mortality and morbidity. BACKGROUND: Despite its potential for reducing morbidity and mortality, OPCAB's role in clinical practice remains controversial. METHODS: A meta-analysis of 37 randomized controlled trials (RCTs) (n = 3,449) and 22 risk-adjusted (logistic regression or propensity-score) observational studies (n = 293,617) was performed. Two reviewers performed literature searches (MEDLINE, EMBASE, PubMed, reference lists), quality assessment, and data extraction. Treatment effects were calculated as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In RCTs, OPCAB was associated with reduced atrial fibrillation (OR 0.59; 95% CI 0.46 to 0.77) and trends toward reduced 30-day mortality (OR 0.91 95% CI 0.45 to 1.83), stroke (OR 0.52; 95% CI 0.25 to 1.05), and myocardial infarction (OR 0.79; 95% CI 0.50 to 1.25). Observational studies showed OPCAB to be associated with reduced 30-day mortality (OR 0.72; 95% CI 0.66 to 0.78), stroke (OR 0.62; 95% CI 0.55 to 0.69), infarction (OR 0.66; 95% CI 0.50 to 0.88), and atrial fibrillation (OR 0.78; 95% CI 0.74 to 0.82). At one to two years, OPCAB was associated with trends toward reduced mortality, but also increased repeat revascularization (RCT: OR 1.75, 95% CI 0.78 to 3.94; Observational: OR 1.35, 95% CI 0.76 to 2.39). CONCLUSIONS: Randomized controlled trials did not find, aside from atrial fibrillation, the statistically significant reductions in short-term mortality and morbidity demonstrated by observational studies. These discrepancies might be due to differing patient-selection and study methodology. Future studies must focus on improving research methodology, recruiting high-risk patients, and collecting long-term data.     

Calcium antagonists are associated with reduced mortality after cardiac surgery: a propensity analysis

OBJECTIVES: Observational studies have questioned the effectiveness of perioperative calcium channel blockers but failed to correct for selection biases. We therefore performed a prospective observational cohort study of the effects of calcium channel blockers on cardiac surgical mortality. A propensity score technique was used for risk adjustment. METHODS: We identified 6619 patients who underwent nontransplant cardiac surgery at the Toronto General Hospital (Toronto, Ontario, Canada) between May 1999 and December 2001. Propensity scores for calcium channel blocker use were constructed for the entire sample and for the subgroup (n = 5222) that underwent coronary artery bypass grafting. The calcium channel blocker adjusted odds ratio for in-hospital mortality after cardiac surgery was determined by using multiple logistic regression and propensity matched-pairs analyses. A subgroup analysis was performed for patients who underwent coronary artery bypass grafting: the calcium channel blocker adjusted odds ratio for mortality was determined by using propensity score matched-pairs analyses. RESULTS: Calcium channel blockers were associated with significantly reduced cardiac surgical mortality after adjustment with both multiple logistic regression (odds ratio, 0.56; 95% confidence interval, 0.33-0.94; P =.028) and propensity score matched-pairs analyses (odds ratio, 0.56; 95% confidence interval, 0.32-0.98; P =.042). Calcium channel blockers were also associated with reduced mortality (odds ratio, 0.48; 95% confidence interval, 0.23-0.98; P =.044) among patients who underwent coronary artery bypass grafting. CONCLUSIONS: After adjustment for baseline differences, calcium channel blockers were associated with significantly reduced mortality after cardiac surgery. This benefit also extends to the subgroup that underwent coronary artery bypass grafting. A large randomized controlled trial of perioperative calcium channel blockers is therefore warranted.     

Improved testing for CMT1A and HNPP using multiplex ligation-dependent probe amplification (MLPA) with rapid DNA preparations: comparison with the interphase FISH method

Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are the two most common peripheral neuropathies, with incidences of about 1 in 2,500. Several techniques can be used to detect the typical 1.5-Mb duplication or deletion associated with these respective conditions, but none combines simplicity with high sensitivity. MLPA is a new technique for measuring sequence dosage. We have assessed its performance for the detection of the specific 1.5-Mb duplication/deletion by prospectively testing 50 patients referred with differential diagnoses of CMT or HNPP. Probes were designed to evaluate the TEKT3, PMP22, and COX10 genes within the CMT1A/HNPP region. We have compared the results with our existing fluorescence in situ hybridization (FISH) assay, which was performed in parallel. There was concordance of results for 49 patients. Of note, one patient showed an intermediate multiplex ligation-dependent probe amplification (MLPA) result with an abnormal FISH result, which is consistent with mosaicism. The assay works equally well with either purified DNA or rapid DNA preparations made by direct cell lysis. The use of the latter significantly reduces the cost of the assay. MLPA is a sensitive, specific, robust, and cost-effective technique suitable for fast, high-throughput testing and offers distinct advantages over other testing methods.     

Latent Human Papillomavirus infection is comparable in the larynx and trachea

Recurrent respiratory papillomas are benign airway tumors caused by Human Papillomaviruses (HPVs) types 6 and 11. The disease is characterized by multiple recurrences of papillomas following surgical removal, caused by activation of latent HPV DNA. Most patients have laryngeal disease, while only a small subset has tracheal involvement. We have asked whether the lower frequency of tracheal papillomas was due to reduced prevalence of latent/subclinical tracheal HPV infection or reduced likelihood of activation to clinically apparent disease. A total of 121 biopsies of clinically normal laryngeal and tracheal tissues from 61 patients with laryngeal papillomas were analyzed for HPV DNA by polymerase chain reaction, confirmed by Southern blot hybridization. Patients were followed for 3-18 years (mean = 5.5 +/- 4.4), with only one developing subsequent tracheal disease. There was no significant difference in prevalence of latent HPV DNA between larynx and trachea, analyzing either those patients with a single biopsy or those with more than one biopsy of larynx, trachea, or both. There was also no significant difference between tracheal latency with HPV 6 and HPV 11. We conclude that HPV infects tracheal mucosa and is maintained as a latent infection in the trachea as efficiently as in the larynx. Therefore, we propose that the low frequency of tracheal disease reflects a lower frequency of HPV activation, and postulate that cellular factors that differ between the stratified squamous epithelium of the larynx and the ciliated pseudo-stratified columnar epithelium of the trachea contribute to this difference.     

Etiology of troponin I elevation in patients with congestive heart failure and low clinical suspicion of myocardial infarction

BACKGROUND: Increased troponin I (TnI) has been detected in congestive heart failure (CHF) patients. We demonstrate that occurrence of LVH, and systolic and diastolic blood pressure values (SBP and DBP, respectively) correlate with increasing levels of serum TnI in a selected CHF population. METHODS: Our team reviewed the medical records of 40 consecutive patients admitted with CHF symptoms, low clinical suspicion of myocardial infarction (MI), and serum TnI measured upon admission. Twenty numerical and categorical parameters were screened. Patients were divided in to seven non-exclusive groups by increasing cutoff values of serum TnI (0, 0.1, 0.2, 0.3, 0.4, 0.6, and 1.5 ng/ml). In each group the average value of numerical parameters and the occurrence of categorical ones were calculated. The correlation between these values and the seven TnI cutoffs were analyzed. RESULTS: Occurrence of electrocardiographic left ventricular hypertrophy (ECG-LVH), and average values of SBP and DBP significantly correlated with the TnI cutoffs by means of multiple regression analysis (P = 0.001, 0.02 and 0.007, respectively). CONCLUSION: ECG-LVH and values of SBP and DBP significantly correlate with increasing cutoff levels of serum TnI in hospitalized patients with CHF and low clinical suspicion of MI.