Dacryocystitis: Systematic Approach to Diagnosis and Therapy

The objective of this paper is to review the main findings of the largest studies on the etiopathogenesis and microbiology of the development of dacryocystitis and to formulate clinical and surgical guidelines based on said studies and on our experience at Cruces Hospital, the Basque Country, Spain. The most common sign of this entity is the distal nasolacrimal duct obstruction, and this should be treated to prevent clinical relapse. The time when surgery should be indicated mainly depends on the clinical signs and symptoms, age and general status of a patient. Given the germs isolated in cases of dacryocystitis, antibiotic therapy against Gram positive (S. aureus, S. pneumoniae, S. epidermidis) and Gram negative bacteria (H. influenzae, P. aeruginosa) should be administered, orally in adults and intravenously in pediatric patients, prior to surgery. Gentamicin and amoxicillin-clavulanic acid have been found to be effective against the bacteria commonly implicated in the etiopathogenesis of this entity.     

Incorporating Budget Impact Analysis in the Implementation of Complex Interventions: A Case of an Integrated Intervention for Multimorbid Patients within the CareWell Study

Objectives

To develop a framework for the management of complex health care interventions within the Deming continuous improvement cycle and to test the framework in the case of an integrated intervention for multimorbid patients in the Basque Country within the CareWell project.

Comparison of different commercial methods for HPV detection in follow-up cytology after ASCUS/LSIL, prediction of CIN2-3 in follow up biopsies and spontaneous regression of CIN2-3

Objective

Different Human Papilloma Virus (HPV) tests are currently used. An integrated comparison of the Amplicor, Cobas4800, PreTect HPV-Proofer and APTIMA HPV tests has not been done.

Methods

We compared the high-risk HPV detection power of these HPV tests in 528 consecutive population-based follow-up Liquid-Based Cytology samples (LBC) after ASCUS/LSIL index cytology. Their sensitivity and specificity to detect HPV in LBC, their predictive values of histopathologic CIN2–3 in follow-up punch biopsies and CIN2–3 regression in the subsequent cones was assessed. The HPV subtypes detected by the Linear Array genotyping-test (LA), PreTect HPV-Proofer and Cobas4800 were also compared. The follow-up histopathology was consensus expert-reviewed and Ki67/p16-supported. The predictive values of the HPV results in LBC by the different tests for presence of CIN2–3 in follow-up biopsies, and regression in subsequent cones, was assessed.

Results

Amplicor, Cobas4800 and APTIMA show good agreement for HPV-positivity/negativity. PreTect HPV-Proofer has many discrepancies versus any of the other methods. The sensitivities for Amplicor, Cobas4800 and APTIMA to detect CIN2–3 were very high (96–100%), but rather low for PreTect HPV-Proofer (53%). Specificity in case of CIN1 or less in follow-up biopsies of Amplicor and Cobas4800 is lower than APTIMA and highest for PreTect HPV-Proofer. HPV subtyping by LA agreed in 90% with Cobas4800 but 70% with PreTect HPV-Proofer.

Conclusions

The Amplicor, Cobas4800 and APTIMA give comparable results but PreTect HPV-Proofer differs from the other tests, with low sensitivity but higher specificity. None of the methods predicted regression of CIN2–3.     

Pregnancy associated plasma protein-A (PAPP-A) is not a marker of the vulnerable atherosclerotic plaque

Objective

To investigate if pregnancy associated plasma protein-A (PAPP-A) was present in the vulnerable plaque, and if not, to find alternative hypothesis for the release of PAPP-A.

Design and methods

Vulnerable plaques and control tissues were examined by immunohistochemistry. Volunteers and patients with non-atherosclerotic disease were examined for release of PAPP-A during ischemia and medical treatment. Non-atherosclerotic tissue samples were examined after incubation with heparins.

Results

We were not able to detect PAPP-A in vulnerable plaques. Patients and volunteers experiencing ischemic events without atherosclerotic lesions only had elevated PAPP-A when treated with heparin. When tissue from normal artery wall was incubated with heparin, PAPP-A was eluted. This was not the case for non-arterial tissue samples.

Conclusion

Elevation of PAPP-A in patients with acute coronary syndromes seems to be caused by heparin induced release of PAPP-A from the arterial wall and not due to excretion from vulnerable plaques.     

Novel 1,2,3-triazole derivatives for use against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain

The purpose of this study was to prepare various 4-substituted N-phenyl-1,2,3-triazole derivatives using click chemistry. The derivatives were screened in vitro for antimicrobial activity against Mycobacterium tuberculosis strain H37Rv (ATCC 27294) using the Alamar Blue susceptibility test. The activity was expressed as the minimum inhibitory concentration (MIC) in μg/mL (μM). Derivatives of isoniazid (INH), (E)-N'-[(1-aryl)-1H-1,2,3-triazole-4-yl)methylene] isonicotinoyl hydrazides, exhibited significant activity with MIC values ranging from 2.5 to 0.62 μg/mL. In addition, they displayed low cytotoxicity against liver cells (hepatoma HepG2) and kidney cells (BGM), thereby providing a high therapeutic index. The results demonstrated the potential and importance of developing new INH derivatives to treat mycobacterial infections.     

Inflammatory effects of highly pathogenic H5N1 influenza virus infection in the CNS of mice

The A/VN/1203/04 strain of the H5N1 influenza virus is capable of infecting the CNS of mice and inducing a number of neurodegenerative pathologies. Here, we examined the effects of H5N1 on several pathological aspects affected in parkinsonism, including loss of the phenotype of dopaminergic neurons located in the substantia nigra pars compacta (SNpc), expression of monoamines and indolamines in brain, alterations in SNpc microglia number and morphology, and expression of cytokines, chemokines, and growth factors. We find that H5N1 induces a transient loss of the dopaminergic phenotype in SNpc and now report that this loss recovers by 90 d after infection. A similar pattern of loss and recovery was seen in monoamine levels of the basal ganglia. The inflammatory response in lung and different regions of the brain known to be targets of the H5N1 virus (brainstem, substantia nigra, striatum, and cortex) were examined at 3, 10, 21, 60, and 90 d after infection. In each of these brain regions, we found a significant increase in the number of activated microglia that lasted at least 90 d. We also quantified expression of IL-1α, IL-1β, IL-2, IL-6, IL-9, IL-10, IL-12(p70), IL-13, TNF-α, IFN-γ, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, eotaxin, interferon-inducible protein 10, cytokine-induced neutrophil chemoattractant, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP) 1α, MIP-1β, and VEGF, and found that the pattern and levels of expression are dependent on both brain region and time after infection. We conclude that H5N1 infection in mice induces a long-lasting inflammatory response in brain and may play a contributing factor in the development of pathologies in neurodegenerative disorders.