Urinary bladder perforation, intra-corporeal knotting, and per-urethral extrusion of ventriculoperitoneal shunt in a single patient: case report and review of literature

Background

Ventriculoperitoneal shunt (VPS) surgery is the most common procedure performed for the treatment of hydrocephalus. Erosive bladder perforation by a peritoneal catheter is an extremely rare complication of VPS. Only ten cases involving the normal (non-augmented) urinary bladder have been reported so far.

Case

We report a case of erosive bladder perforation, intra-corporeal knot formation, and perurethral extrusion of the distal end of VPS. This is the second only case report so far in the world literature showing triad of uncommon VPS complications in a single patient.

Conclusion

Prompt management could avoid further complications. Patient’s parents should be aware about this rare complication, so that they can seek timely medical help.     

Strategic protein target analysis for developing drugs to stop dental caries

Dental caries is the most common disease to cause irreversible damage in humans. Several therapeutic agents are available to treat or prevent dental caries, but none besides fluoride has significantly influenced the disease burden globally. Etiologic mechanisms of the mutans group streptococci and specific Lactobacillus species have been characterized to various degrees of detail, from identification of physiologic processes to specific proteins. Here, we analyze the entire Streptococcus mutans proteome for potential drug targets by investigating their uniqueness with respect to non-cariogenic dental plaque bacteria, quality of protein structure models, and the likelihood of finding a drug for the active site. Our results suggest specific targets for rational drug discovery, including 15 known virulence factors, 16 proteins for which crystallographic structures are available, and 84 previously uncharacterized proteins, with various levels of similarity to homologs in dental plaque bacteria. This analysis provides a map to streamline the process of clinical development of effective multispecies pharmacologic interventions for dental caries.     

Copper mediated one-pot synthesis of quinazolinones and exploration of piperazine linked quinazoline derivatives as anti-mycobacterial agents

A facile method was developed for the synthesis of quinazolinone derivatives in a one-pot condensation reaction via in situ amine generation using ammonia as the amine source and with the formation of four new C–N bonds in good to excellent yields. With the optimised method, we synthesized a library of piperazine linked quinazoline derivatives and the synthesized compounds were evaluated for their inhibitory activity against Mycobacterium tuberculosis. The compounds 8b, 8e, 8f, 8m, 8n and 8v showed potent anti-mycobacterial activity with MIC values of 2–16 μg mL⁻¹. All the synthesized compounds follow Lipinski''s rules for drug likeness.

A facile method was developed for the synthesis of quinazolinone derivatives in a one-pot condensation reaction via in situ amine generation using ammonia as the amine source and with the formation of four new C–N bonds in good to excellent yields.     

Biomarkers in sarcoidosis

Introduction: Numerous biomarkers have been evaluated for the diagnosis, assessment of disease activity, prognosis, and response to treatment in sarcoidosis. In this report, we discuss the clinical and research utility of several biomarkers used to evaluate sarcoidosis.

Areas covered: The sarcoidosis biomarkers discussed include serologic tests, imaging studies, identification of inflammatory cells and genetic analyses. Literature was obtained from medical databases including PubMed and Web of Science.

Expert commentary: Most of the biomarkers examined in sarcoidosis are not adequately specific or sensitive to be used in isolation to make clinical decisions. However, several sarcoidosis biomarkers have an important role in the clinical management of sarcoidosis when they are coupled with clinical data including the results of other biomarkers.     

Human monoclonal antibody AVP-21D9 to protective antigen reduces dissemination of the Bacillus anthracis Ames strain from the lungs in a rabbit model

Dutch-belted and New Zealand White rabbits were passively immunized with AVP-21D9, a human monoclonal antibody to protective antigen (PA), at the time of Bacillus anthracis spore challenge using either nasal instillation or aerosol challenge techniques. AVP-21D9 (10 mg/kg) completely protected both rabbit strains against lethal infection with Bacillus anthracis Ames spores, regardless of the inoculation method. Further, all but one of the passively immunized animals (23/24) were completely resistant to rechallenge with spores by either respiratory challenge method at 5 weeks after primary challenge. Analysis of the sera at 5 weeks after primary challenge showed that residual human anti-PA levels decreased by 85 to 95%, but low titers of rabbit-specific anti-PA titers were also measured. Both sources of anti-PA could have contributed to protection from rechallenge. In a subsequent study, bacteriological and histopathology analyses revealed that B. anthracis disseminated to the bloodstream in some na?ve animals as early as 24 h postchallenge and increased in frequency with time. AVP-21D9 significantly reduced the dissemination of the bacteria to the bloodstream and to various organs following infection. Examination of tissue sections from infected control animals, stained with hematoxylin-eosin and the Gram stain, showed edema and/or hemorrhage in the lungs and the presence of bacteria in mediastinal lymph nodes, with necrosis and inflammation. Tissue sections from infected rabbits dosed with AVP-21D9 appeared comparable to corresponding tissues from uninfected animals despite lethal challenge with B. anthracis Ames spores. Concomitant treatment with AVP-21D9 at the time of challenge conferred complete protection in the rabbit inhalation anthrax model. Early treatment increased the efficacy progressively and in a dose-dependent manner. Thus, AVP-21D9 could offer an adjunct or alternative clinical treatment regimen against inhalation anthrax.     

Setting priorities in global child health research investments: assessment of principles and practice

This article reviews theoretical and practical approaches for setting priorities in global child health research investments. It also provides an overview of previous attempts to develop appropriate tools and methodologies to define priorities in health research investments. A brief review of the most important theoretical concepts that should govern priority setting processes is undertaken, showing how different perspectives, such as medical, economical, legal, ethical, social, political, rational, philosophical, stakeholder driven, and others will necessarily conflict each other in determining priorities. We specially address present research agenda in global child health today and how it relates to United Nation's (UN) Millennium Development Goal 4, which is to reduce child mortality by two-thirds between 1990 and 2015. The outcomes of these former approaches are evaluated and their benefits and shortcomings presented. The case for a new methodology for setting priorities in health research investments is presented, as proposed by Child Health and Nutrition Research Initiative, and a need for its implementation in global child health is outlined. A transdisciplinary approach is needed to address all the perspectives from which investments into health research can be seen as priorities. This prioritization requires a process that is transparent, systematic, and that would take into account many perspectives and build on advantages of previous approaches.     

Setting priorities in global child health research investments: addressing values of stakeholders

Aim

To identify main groups of stakeholders in the process of health research priority setting and propose strategies for addressing their systems of values.

Methods

In three separate exercises that took place between March and June 2006 we interviewed three different groups of stakeholders: 1) members of the global research priority setting network; 2) a diverse group of national-level stakeholders from South Africa; and 3) participants at the conference related to international child health held in Washington, DC, USA. Each of the groups was administered different version of the questionnaire in which they were asked to set weights to criteria (and also minimum required thresholds, where applicable) that were a priori defined as relevant to health research priority setting by the consultants of the Child Health and Nutrition Research initiative (CHNRI).

Results

At the global level, the wide and diverse group of respondents placed the greatest importance (weight) to the criterion of maximum potential for disease burden reduction, while the most stringent threshold was placed on the criterion of answerability in an ethical way. Among the stakeholders’ representatives attending the international conference, the criterion of deliverability, answerability, and sustainability of health research results was proposed as the most important one. At the national level in South Africa, the greatest weight was placed on the criterion addressing the predicted impact on equity of the proposed health research.

Conclusions

Involving a large group of stakeholders when setting priorities in health research investments is important because the criteria of relevance to scientists and technical experts, whose knowledge and technical expertise is usually central to the process, may not be appropriate to specific contexts and in accordance with the views and values of those who invest in health research, those who benefit from it, or wider society as a whole.When decisions on investments in health research are made, the term “stakeholders” refers to all individuals and/or groups who have interest in prioritization of those investments. The stakeholders will therefore comprise a large and highly heterogeneous group. Some apparent examples may include research funding agencies (eg, governmental agencies, private organizations, public-private partnerships, international and regional organizations, and taxpayers of a certain region), direct recipients of the funding (eg, researchers and research institutions), beneficiaries of the research (eg, policy makers and the general population of a country), and any other group with interest in prioritization process (eg, advocacy groups, journalists and media, lawyers, economists, experts in ethics, and many others).Two fundamental characteristics of any acceptable and successful priority setting process are legitimacy and fairness (1). In order to ensure the legitimacy and fairness of the priority setting decisions in health research investments, involvement of a wide range of stakeholders (and/or eliciting their values) is needed. Unfortunately, health research priorities are presently mainly driven by technical experts (2-5). The results of prioritization are therefore in danger of being mostly influenced by their personal views, with minimal input from representatives from the wider community who also may have interest in the process but lack technical expertise. Since the values and criteria important to scientists and technical experts may vary remarkably from those of other relevant stakeholders (6-8), the relevance of eliciting wider stakeholders’ input is increasingly being acknowledged (9-11). However, the main challenge is to develop a systematic, flexible, and repeatable strategy on how this can be achieved in different contexts.The literature on priority setting for health interventions identifies two main strategies: 1) stakeholders’ values may impact decisions through procedural processes (by having access to the decisions and the rationales behind the decisions, and by having the authority to deliberate on the decisions and influence the final outcome); 2) stakeholders’ values can be directly elicited using quantitative methods (through surveys where respondents rank, weigh, or rate their values) and qualitative methods (involving individual interviews, Delphi technique, complaints procedures or group discussions, concept mapping, citizen’s jury, and public meetings) (12). The main challenges in those attempts have mainly been the lack of capacity for some stakeholders to engage in meaningful deliberations (13) and how to practically incorporate the elicited stakeholders’ values in decision-making (12,14). This paper presents our suggestions and experiences on how the values and interests of large and diverse group of stakeholders could still be incorporated in decisions on health research investment priorities. We specified thresholds and weights needed to address stakeholders’ values within CHNRI methodology using three different versions of a questionnaire. We aimed to assess stakeholders’ values for priority setting in global health research investments. We tested questionnaires that presented different levels of complexity and detail of the questions that stakeholders’ representatives would be asked. We also aimed to evaluate different strategies of turning their responses into numerical thresholds and weights.     

Bacteriological evaluation of conjunctiva, contact lens storage cases and solutions during contact lens wear

A total of 90 subjects were investigated in this study, out of which 51 constituted the contact lens wearing group and 39 constituted the control group who had never worn contact lenses. Out of 51 contact lens wearing group, 41 were asymptomatic lens wearer subjects and 10 were symptomatic lens wearer subjects having some complications. All the subjects of contact lens wearing group had worn soft contact lenses on daily wear basis for a duration of 7 days to one year. In total 33 subjects were culture positive and remaining 57 culture negative. Staphylococcus epidermidis was isolated equally from asymptomatic and control group, however, significantly more gram negative organisms such as Pseudomonas aeruginosa and Serratia marcescens were isolated from the symptomatic lens wearers. P. aeruginosa and S. marcescens could also be isolated from lens storage cases. S. marcescens was the organism most commonly isolated from the contact lens solutions. Further, the results showed that both P. aeruginosa and S. marcescens adhere to injured cornea only and not to normal cornea when microscopic study of adherence of bacteria to uninjured and injured ex vivo mouse corneas was done.     

Epithelioid hemangioma of the temporal artery: a case report

Temporal or giant cell arteritis is the most common vasculitis affecting the temporal artery. We encountered an unusual case of involvement of the temporal artery, which showed marked proliferating capillaries admixed with a dense infiltrate of eosinophils affecting all layers of the vessel. It was concluded that these changes were those of an epithelioid hemangioma of the temporal artery.