Molecular characterization of adenoviral infections in Cuba: report of an unusual association of species D adenoviruses with different clinical syndromes

Adenoviruses are common pathogens that are responsible for a wide variety of infectious syndromes. The objectives of this study were to identify and characterize members of different adenovirus species at the molecular level and to describe the correlation between viruses and clinical syndromes during a period of 4 years. Between 2002 and 2006, 45 of 512 respiratory specimens (8%) from patients with acute respiratory tract infection tested positive for adenovirus. Four adenovirus isolates from samples sent for enterovirus isolation were also analyzed. This research identified 49 confirmed cases of human adenovirus infection by PCR and/or viral culture. The most common diagnosis was upper respiratory infection (44%). Human adenovirus D was the major species found (59%), followed by Human adenovirus C (36%) and Human adenovirus B (4%). Human adenovirus 5 was the major serotype found producing bronchiolitis, followed by human adenovirus 6. In patients with upper respiratory infection, the major serotype found was human adenovirus 17. Viruses of the species Human adenovirus D were identified in seven (77%) cases of acute febrile syndrome. Four isolates from clinical materials obtained from patients with encephalitis, acute flaccid paralysis and meningoencephalitis were identified as belonging to the species Human adenovirus D. Our data demonstrate a surprising result about the identification of an unusual association of viruses of the species Human adenovirus D with different clinical syndromes. This observation could be evaluated as a possible indicator of the emergence of a novel strain but further studies are required.     

Effect of polysorbate 80 on oritavancin binding to plastic surfaces: implications for susceptibility testing

Oritavancin, a semisynthetic lipoglycopeptide with activity against gram-positive bacteria, has multiple mechanisms of action, including the inhibition of cell wall synthesis and the perturbation of the membrane potential. Approved guidelines for broth microdilution MIC assays with dalbavancin, another lipoglycopeptide, require inclusion of 0.002% polysorbate 80. To investigate the potential impact of polysorbate 80 on oritavancin susceptibility assays, we quantified the recovery of [(14)C]oritavancin from susceptibility assay plates with and without polysorbate 80 and examined the effect of the presence of polysorbate 80 on the oritavancin MICs for 301 clinical isolates from the genera Staphylococcus, Enterococcus, and Streptococcus. In the absence of polysorbate 80, [(14)C]oritavancin was rapidly lost from solution in susceptibility assay test plates: 9% of the input drug was recovered in broth at 1 h when [(14)C]oritavancin was tested at 1 mug/ml. Furthermore, proportionately greater losses were observed at lower oritavancin concentrations, suggesting saturable binding of oritavancin to surfaces. The inclusion of 0.002% polysorbate 80 or 2% lysed horse blood permitted the recovery of 80 to 100% [(14)C]oritavancin at 24 h for all drug concentrations tested. Concordantly, oritavancin MIC(90)s for streptococcal isolates, as determined in medium containing 2% lysed horse blood, were identical with and without polysorbate 80. In stark contrast, polysorbate 80 reduced the oritavancin MIC(90)s by 16- to 32-fold for clinical isolates of enterococci and staphylococci, which are typically cultured without blood. The results presented here provide evidence that the MIC data for oritavancin in the current literature significantly underestimate the potency of oritavancin in vitro. Moreover, the combination of data from MIC and [(14)C]oritavancin recovery studies supports the revision of the oritavancin broth microdilution method to include polysorbate 80 throughout the assay.     

Long-term versus short-term clopidogrel therapy in patients undergoing coronary stenting (from the Randomized Argentine Clopidogrel Stent [RACS] trial)

The optimal duration of treatment with clopidogrel after percutaneous coronary intervention (PCI) with stent placement remains controversial. The Randomized Argentine Clopidogrel Stent (RACS) trial was a prospective, randomized, nonblinded study of 1,004 patients undergoing PCI who were randomized after successful bare metal stent placement to 30 versus 180 days of clopidogrel; all patients also received aspirin. Patients were eligible regardless of whether they had presented with ST-elevation myocardial infarction (MI), acute coronary syndrome, or stable angina. The primary end point was a composite of death, MI, and stroke at 180 days. Baseline clinical characteristics showed no differences between groups in terms of age, gender, history, risk factors, or incidence of diabetes; 72% presented with an acute coronary syndrome and 15% had MI as the indication for PCI. At hospital discharge and 30 days, when the 2 groups received the same treatment, there were no significant differences between groups in frequency of death, MI, or stroke. However, from 30 days to 6 months, patients assigned to 6 months of clopidogrel reached the primary end point of death, MI, and stroke less frequently (4.99% vs 1.74%, p = 0.010, relative risk decrease 65%). No significant between-group differences were found in frequency of total bleeding (0.64% vs 1.52%, p = 0.34) for the control and study groups. In conclusion, after successful placement of a bare metal stent in a coronary artery, patients treated with 6 months of clopidogrel showed a trend toward fewer adverse events compared with those treated for 30 days.     

Comparison of Central and Extended Left Pancreatectomy for Lesions of the Pancreatic Neck

Background  Central pancreatectomy (CP) is a parenchyma-sparing alternative to extended left pancreatectomy (ELP) for tumors of the pancreatic neck. We compared short- and long-term outcomes for the two approaches. Methods  Patients who underwent CP or ELP from 2000–2007 for neoplasms of the neck were identified. Charts were reviewed for patient, treatment, and outcome data. Long-term and quality-of-life (QoL) data were gathered through Institutional Review Board (IRB)-approved telephone interviews and questionnaires European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and QLQ-PAN26. Results  31 patients were identified; 13 underwent CP and 18 underwent ELP. Median follow-up was 29 months (range 5–90). Groups did not differ in age, American Society of Anesthesiologists (ASA) class, or preexisting diabetes mellitus (DM). CP patients had less gland resected (5.7 ± 2.1 cm versus 10.8 ± 2.8 cm) and lower postoperative mean blood glucose levels (120 ± 15 mg/dl versus 136 ± 24 mg/dl). CP patients experienced more complications (92% versus 39%), but no significant difference in major complications (38%, CP versus 17%, ELP; P = 0.17) or hospital stay (9 ± 3 days, CP versus 7.5 ± 4 days, ELP). There was one perioperative death in the CP group, unrelated to surgical technique. Questionnaire analysis showed no differences in functional or symptom scales. New-onset exocrine insufficiency was not significantly different between the groups (10%, CP versus 27%, ELP; P = 0.62), but the ELP group had a higher rate of new-onset DM (57% versus 11%; P = 0.04). Conclusion  CP is associated with more complications than ELP, but no difference in long-term QoL. Due to the lower incidence of postoperative DM, CP can be recommended for healthy patients with indolent tumors of the pancreatic neck. Electronic Supplementary Material  Supplementary material is available for this article at doi: and is accessible for authorized users. Presented at the Society of Surgical Oncology Chicago, IL March 15, 2008     

A phase I trial of intravenous infusion of ONYX-015 and enbrel in solid tumor patients

ONYX-015 is an attenuated chimeric human group C adenovirus, which preferentially replicates in and lyses tumor cells that are p53 negative. The purpose of this phase I, dose-escalation study was to determine the safety and feasibility of intravenous infusion with ONYX-015 in combination with enbrel in patients with advanced carcinoma. Enbrel is a recombinant dimer of human tumor-necrosis factor (TNF)-alpha receptor, previously shown to reduce the level of functional TNF. Nine patients, three in each cohort received multiple cycles of ONYX-015 infusion (1 x 10(10), 1 x 10(11) and 1 x 10(12) vp weekly for 4 weeks/cycle) in addition to subcutaneous enbrel (only during cycle 1) injections per FDA-indicated dosing. Of the nine patients, four had stable disease. No significant adverse events were attributed to the experimental regimen, confirming that enbrel can be safely administered along with oncolytic virotherapy. Two of the three patients in cohort 3 had detectable viral DNA at days 3 and 8 post-ONYX-015 infusion. Their detectable circulating viral DNA was markedly higher during cycle 1 (with enbrel coadministration) as compared with cycle 2 (without enbrel) at the same time points. Area under the curve determinations indicate a marked higher level of TNF-alpha induction and accelerated clearance at cycle 2 in the absence of enbrel. Further assessment is recommended.     

Pulmonary phagocyte depression induced by an acid or alkaline solution in a rat model of peritonitis

BACKGROUND: Peritonitis is a surgical problem with a high mortality rate attributable to various complications, including respiratory infection. This complication is more common under certain conditions reflective of the origin of peritonitis, suggesting that the composition of the peritoneal fluid exerts an influence on the intensity of the macrophage and peritoneal response. To establish a correlation among macrophage function, absorption of bacteria from the peritoneal cavity, and the pH of the peritoneal fluid, we carried out this study. METHODS: Thirty female Wistar rats were divided into three equal groups, all of which received infusions of 0.9% saline by parietal puncture. In group A (control), the saline pH was 7.0; in group B, it was 2.5; and in group C, it was 8.5. After 40 min, 0.25 mL of a suspension containing 10(11) colony-forming units of (99m)Tc-labeled Escherichia coli was infused by the same route. After another 40 min, samples of vena caval blood, spleen, liver, and lung were removed; the radioactivity was counted; bacterial absorption was determined; and the proportional radioactivity/g of tissue was calculated. The values were compared among the groups by the Student t-test, with the level of significance set at p < 0.05. RESULTS: There was significantly greater bacterial absorption in group B than in group C (p = 0.004) but no differences in the numbers of bacteria in the liver and spleen. Bacteria were significantly more numerous in the peripheral blood in group B than in groups A and C (p = 0.04 for both). Pulmonary phagocytosis was significantly reduced in group B compared with group A (p = 0.008) and group C (p = 0.005). CONCLUSION: Peritonitis associated with acidic conditions in the peritoneal cavity is correlated with a reduction in pulmonary phagocytosis and an increase in the numbers of nonphagocytized bacteria in the peripheral blood, possibly representing a direct or indirect cause of the higher incidence of pneumonia and sepsis in these individuals.     

Are all echocardiographic findings equally predictive for diagnosis in prosthetic endocarditis?

OBJECTIVE: The purpose of this study was to analyze the predictive value of different anatomic echocardiographic findings for diagnosis of prosthetic endocarditis. BACKGROUND: Prognosis in endocarditis has improved in recent years after the wide acceptance of new clinical diagnostic criteria. One of the most important issues in clinical diagnosis is to use echocardiography for identification of endocardial involvement, but prosthetic material impairs echo quality. METHODS: In all, 49 patients with 58 episodes of suggested prosthetic endocarditis were prospectively studied using transthoracic and transesophageal echocardiography. The patients were divided into two groups: group A, patients with 34 episodes of definite endocarditis according to Durack's criteria; and group B, patients with 24 episodes who were eventually classified as not having endocarditis, either by surgical exploration or by a mean of 32.6 months (range: 8-38 months) of follow-up. RESULTS: In group A, valve dehiscence was observed in 4 episodes of suggested endocarditis, pseudoaneurysms in 3, fistulae in 2, and moderate to severe perivalvular regurgitation in 15. No patient in group B had these abnormalities (P <.001). Vegetations were present in 17 episodes in group A (50%) versus 1 in group B (9%; P <.001); perivalvular abscesses were seen in 19 episodes in group A (56%) versus 1 in group B (P <.001). Mild perivalvular regurgitation was observed in only 1 episode for group A (3%) and in 14 episodes for group B (58%; P <.01). The presence of any of the above echocardiographic finding, when used in combination with the exclusion of mild perivalvular regurgitation, had a positive and negative predictive value for diagnosing endocarditis of 94% and 96%, respectively. Isolated mild perivalvular regurgitation had a poor positive predictive value (6%). CONCLUSION: Isolated mild perivalvular regurgitation should not be used as diagnostic criteria in patients with suggested prosthetic valve endocarditis.