Epstein-Barr virus-associated B-cell proliferations of diverse clonal origins after bone marrow transplantation in a 12-year-old patient with severe combined immunodeficiency

A 12-year-old boy with severe combined immunodeficiency who had been kept in a gnotobiotic environment since birth received bone marrow from a histoincompatible sibling in an attempt to reconstitute immunologic function. To prevent graft versus host disease, the donor's marrow was treated in vitro with monoclonal antibody and complement to remove alloreactive T cells. Eighty days after transplantation, the patient had a systemic illness characterized by fever, thrombocytopenia, gastrointestinal pain, and bleeding; he died on the 124th post-transplantation day. Postmortem examination revealed multiple tumor-like B-cell proliferations, recipient in origin, in numerous organs. Epstein-Barr virus (EBV) was isolated from the patient's pharyngeal secretions; EBV nuclear antigen was found in spontaneously transformed peripheral-blood lymphocytes, inflammatory cells from peritoneal fluid, and bone marrow cells; and EBV genomes were discovered in all tumor tissues. The donor's serum showed evidence of past EBV infection. Analysis of cellular immunoglobulin and immunoglobulin gene DNA from the tumors indicated both monoclonal and oligoclonal B-cell proliferations. These findings provide evidence for the evolution of EBV-induced polyclonal activation of B cells to oligoclonal B-cell proliferation and finally to monoclonal B-cell lymphoma.     

Chemical resistance of the gram-negative bacteria to different sanitizers in a water purification system

Background  

Purified water for pharmaceutical purposes must be free of microbial contamination and pyrogens. Even with the additional sanitary and disinfecting treatments applied to the system (sequential operational stages), Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas alcaligenes, Pseudomonas picketti, Flavobacterium aureum, Acinetobacter lowffi and Pseudomonas diminuta were isolated and identified from a thirteen-stage purification system. To evaluate the efficacy of the chemical agents used in the disinfecting process along with those used to adjust chemical characteristics of the system, over the identified bacteria, the kinetic parameter of killing time (D-value) necessary to inactivate 90% of the initial bioburden (decimal reduction time) was experimentally determined.     

Organ donation and transplant: The Islamic perspective

Islam is the second most practiced religion globally, and the number of Muslims in Western countries has been increasing due to recent trends in migration. Studies have shown that Muslims in the Western world have more negative attitudes toward organ donation and transplantation compared with individuals from other religious backgrounds. Multiple barriers have been postulated that may prevent Muslims from exploring organ donation or transplantation. We conducted a literature review with the goal of summarizing the opinions of major Sunni and Shia scholars and Islamic bodies about organ donation and transplantation, including their opinions and rulings on the neurological determination of death to inform healthcare professionals, community members, and leaders. We also identified factors and attitudes that may prevent members of the Muslim community from achieving equitable access to transplantation or from consenting to donate organs during life or after death. Key factors or concerns identified included: lack of information regarding organ donation, mistrust of the healthcare system, family opinions, sacredness of the body, lack of clear understanding of religious rulings, and opinions of religious leaders. Studies have suggested that partnering with religious leaders to address these concerns may help foster positive attitudes toward organ donation and transplantation.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

A familial lymphoproliferative disorder presenting with primary pulmonary manifestations.

A familial lymphoproliferative disorder presented in three male siblings with primary pulmonary involvement manifested as either lymphoid interstitial pneumonia or an angiodestructive polymorphous infiltrate morphologically resembling lymphomatoid granulomatosis. The polymorphous infiltrate consisted chiefly of mature T-cells with a few B-cells and plasma cells, and gene rearrangement studies failed to show clonality. Epstein-Barr virus, frequently associated with proliferative lesions in males in the X-linked lymphoproliferative syndrome, was not demonstrated in any of the pulmonary lesions. An HLA haplotype shared among the affected siblings was A1, B8, DR4. The unusual clinical presentation plus the lack of involvement by EBV in the pulmonary lesions suggests that this is a previously undescribed familial lymphoproliferative disorder.     

Demand and access to mental health services: a qualitative formative study in Nepal

Background

Nepal is experiencing a significant ‘treatment gap’ in mental health care. People with mental disorders do not always receive appropriate treatment due to a range of structural and individual issues, including stigma and poverty. The PRIME (Programme for Improving Mental Health Care) programme has developed a mental health care plan to address this issue in Nepal and four other low and middle income countries. This study aims to inform the development of this comprehensive care plan by investigating the perceptions of stakeholders at different levels of the care system in the district of Chitwan in southern Nepal: health professionals, lay workers and community members. It focuses specifically on issues of demand and access to care, and aims to identify barriers and potential solutions for reaching people with priority mental disorders.

Methods

This qualitative study consisted of key informant interviews (33) and focus group discussions (83 participants in 9 groups) at community and health facility levels. Data were analysed using a framework analysis approach.

Results

As well as pragmatic barriers at the health facility level, mental health stigma and certain cultural norms were found to reduce access and demand for services. Respondents perceived the lack of awareness about mental health problems to be a major problem underlying this, even among those with high levels of education or status. They proposed strategies to improve awareness, such as channelling education through trusted and respected community figures, and responding to the need for openness or privacy in educational programmes, depending on the issue at hand. Adapting to local perceptions of stigmatised treatments emerged as another key strategy to improve demand.

Conclusions

This study identifies barriers to accessing care in Nepal that reach beyond the health facility and into the social fabric of the community. Stakeholders in PRIME’s integrated care plan advocate strategic awareness raising initiatives to improve the reach of integrated services in this low-income setting.

     

Sirolimus-based calcineurin inhibitor withdrawal immunosuppressive regimen in kidney transplantation: a single center experience

Background/aim  

This observational study was conducted to evaluate the safety and efficacy of the conversion from calcineurin inhibitors (CNIs) to sirolimus (SRL)-based immunosuppressive therapy in kidney transplantation.