Recognition of synthetic polypeptides corresponding to the N- and C-terminal fragments of Plasmodium falciparum Exp-1 by T-cells and plasma from human donors from African endemic areas

The present work describes the recognition of three synthetic polypeptides encompassing the N- and C-terminal regions of the transmembrane Exp-1 protein of the parasite Plasmodium falciparum by plasma and peripheral blood mononuclear cells from naturally exposed individuals living in African endemic areas. The three polypeptides comprise the sequences 23-105, 73-162 and 101-162, and overlap at the transmembrane domain (73-105). Thus, they permitted characterization of the immune response specific to the N- and C-terminal domains in an independent fashion. Two different populations were evaluated, one in the village of Safo in Mali and the other in the villages of Somnaway, Kabortenga and Toussouktenga in Burkina Faso. Antibodies to the sequence 73-162 of Pf Exp-1 were found in 70% of adult Mali donors and in all of the donors tested from Burkina Faso. Strikingly, the N-terminal fragment Pf Exp-1 23-105 was only weakly recognized by a few donors. Evaluation of the T-cell response indicated that the peptide Pf Exp-1 23-105 was more potent than Pf Exp-1 73-162 in inducing a proliferative response. A correlation between peptide-specific interferon-gamma and interleukin-6 production and proliferation to peptide Pf Exp-1 23-105 was observed. Further studies are needed to evaluate this molecule as a vaccine candidate.     

Trends in incidence,treatment and survival of aggressive B-cell lymphoma in the Netherlands 1989–2010

Only a small number of patients with aggressive B-cell lymphoma take part in clinical trials, and elderly patients in particular are under-represented. Therefore, we studied data of the population-based nationwide Netherlands Cancer Registry to determine trends in incidence, treatment and survival in an unselected patient population. We included all patients aged 15 years and older with newly diagnosed diffuse large B-cell lymphoma or Burkitt lymphoma in the period 1989–2010 and mantle cell lymphoma in the period 2001–2010, with follow up until February 2013. We examined incidence, first-line treatment and survival. We calculated annual percentage of change in incidence and carried out relative survival analyses. Incidence remained stable for diffuse large B-cell lymphoma (n=23,527), while for mantle cell lymphoma (n=1,634) and Burkitt lymphoma (n=724) incidence increased for men and remained stable for women. No increase in survival for patients with aggressive B-cell lymphoma was observed during the period 1989–1993 and the period 1994–1998 [5-year relative survival 42% (95%CI: 39%–45%) and 41% (38%–44%), respectively], but increased to 46% (43%–48%) in the period 1999–2004 and to 58% (56%–61%) in the period 2005–2010. The increase in survival was most prominent in patients under 65 years of age, while there was a smaller increase in patients over 75 years of age. However, when untreated patients were excluded, patients over 75 years of age had a similar increase in survival to younger patients. In the Netherlands, survival for patients with aggressive B-cell lymphoma increased over time, particularly in younger patients, but also in elderly patients when treatment had been initiated. The improvement in survival coincided with the introduction of rituximab therapy and stem cell transplantation into clinical practice.     

Rare CpG island methylator phenotype in ulcerative colitis-associated neoplasias

BACKGROUND & AIMS: We previously reported that a high degree of age-related methylation was found in both the dysplastic and nondysplastic mucosa of patients with ulcerative colitis (UC). Whether this translates into hypermethylation in UC-associated cancers (UC-Cs) is not known. METHODS: We evaluated the methylation status of 11 genes (MINT1, 2, 31, hMLH1, p16, p14, MGMT, HPP1, SFRP1, ERalpha, and LINE-1) in 48 UC-Cs, 21 UC-associated dysplasias, and 69 sporadic colorectal cancers (S-CRCs) using a quantitative bisulfite pyrosequencing analysis. RESULTS: Methylation levels in UC-Cs were lower than S-CRCs for all the genes except MGMT. A methylation index based on the average of Z-scores, for type C (cancer-specific genes: MINT1, MINT2, MINT31, hMLH1, p16, and p14) was -.97 in UC-Cs and .92 in S-CRCs (P = .009). That of type A (age-related genes: HPP1, SFRP1, and ERalpha) was -1.97 in UC-Cs and 1.24 in S-CRCs (P < .001). We observed a significant difference in the incidence of CpG island methylator phenotype between UC-Cs and S-CRCs (8 of 48 [17%] and 26 of 69 [38%]; P = .022). UC-associated dysplasias had significantly higher methylation of type A gene than UC-Cs (Z-score: .07 and -1.97, respectively; P < .001). By contrast, global DNA methylation measured using a LINE-1 assay was significantly higher in UC-Cs than in S-CRCs (58.2% vs 51.0%, P < .001). CONCLUSIONS: DNA methylation alterations are uncommon in UC cancers. Given that both genetic and epigenetic changes are common in UC mucosa and dysplasias, we speculate that the genetic changes lead to a more aggressive clinical course than epigenetic changes.     

Clinical and Scintigraphic Assessment of Swallowing of Older Patients Admitted to a Tertiary Care Geriatric Ward

This study aimed to verify if older patients admitted to a tertiary care geriatric ward with no spontaneous complaints of dysphagia have impaired swallowing function as detected by a specialized clinical assessment and a scintigraphic study of swallowing. Thirty patients (mean age = 76.2 years, 17 women), consecutively admitted for the treatment of acute or chronic diseases, were studied. Two control groups were also studied, one consisting of 10 healthy older persons (mean age = 69.6 years, 5 women) and the other consisting of 20 young volunteers (mean age = 25.4 years, 11 women). A complete clinical assessment of swallowing was performed by a speech pathologist. Each subject was also submitted to scintigraphic studies of oropharyngeal transit after swallowing liquid and syrup boluses labeled with ^99mtechnetium phytate. Transit time, clearance time, and residuals were measured. Five patients had impairments in swallowing function detected by clinical assessment, three of them in the absence of complaints even after specific questioning. Scintigraphic transit times did not differ between the groups studied; however, residuals after syrup swallows were greater in the patient group compared with the healthy older volunteers. These findings suggest an increased risk for aspiration and the usefulness of a brief assessment of swallowing function in all patients admitted to tertiary care geriatric wards.     

[99mTc]MIBI SPECT/CT for Identifying Dystonic Muscles in Patients with Primary Cervical Dystonia

Molecular Imaging and Biology - This study aimed to evaluate the usefulness of [99mTc]sestamibi ([99mTc]MIBI) single photon emission computed tomography (SPECT)/X-ray computed tomography (CT)...     

Phase 1/2 study of the combination of 5-aza-2'-deoxycytidine with valproic acid in patients with leukemia

We conducted a phase 1/2 study of the combination of 5-aza-2'-deoxycytidine (decitabine) and the histone deacetylase inhibitor valproic acid (VPA) in patients with advanced leukemia, including older untreated patients. A group of 54 patients were treated with a fixed dose of decitabine (15 mg/m(2) by IV daily for 10 days) administered concomitantly with escalating doses of VPA orally for 10 days. A 50 mg/kg daily dose of VPA was found to be safe. Twelve (22%) patients had objective response, including 10 (19%) complete remissions (CRs), and 2 (3%) CRs with incomplete platelet recovery (CRp). Among 10 elderly patients with acute myelogenous leukemia or myelodysplastic syndrome, 5 (50%) had a response (4CRs, 1CRp's). Induction mortality was observed in 1 (2%) patient. Major cytogenetic response was documented in 6 of 8 responders. Remission duration was 7.2 months (range, 1.3-12.6+ months). Overall survival was 15.3 months (range, 4.6-20.2+ months) in responders. Transient DNA hypomethylation and global histone H3 and H4 acetylation were induced, and were associated with p15 reactivation. Patients with lower pretreatment levels of p15 methylation had a significantly higher response rate. In summary, this combination of epigenetic therapy in leukemia was safe and active, and was associated with transient reversal of aberrant epigenetic marks.     

Ebola Viral Hemorrhagic Disease Outbreak in West Africa- Lessons from Uganda

Background

There has been a rapid spread of Ebola Viral Hemorrhagic disease in Guinea, Liberia and Sierra Leone since March 2014. Since this is the first time of a major Ebola outbreak in West Africa; it is possible there is lack of understanding of the epidemic in the communities, lack of experience among the health workers to manage the cases and limited capacities for rapid response. The main objective of this article is to share Uganda''s experience in controlling similar Ebola outbreaks and to suggest some lessons that could inform the control of the Ebola outbreak in West Africa.

Methods

The article is based on published papers, reports of previous Ebola outbreaks, response plans and experiences of individuals who have participated in the control of Ebola epidemics in Uganda.Lessons learnt: The success in the control of Ebola epidemics in Uganda has been due to high political support, effective coordination through national and district task forces. In addition there has been active surveillance, strong community mobilization using village health teams and other community resources persons, an efficient laboratory system that has capacity to provide timely results. These have coupled with effective case management and infection control and the involvement of development partners who commit resources with shared responsibility.

Conclusion

Several factors have contributed to the successful quick containment of Ebola outbreaks in Uganda. West African countries experiencing Ebola outbreaks could draw some lessons from the Uganda experience and adapt them to contain the Ebola epidemic.