Ultrasound and Doppler findings in a rare case of Castleman's disease of the parotid

Castleman''s disease of the parotid gland is an extremely rare entity, with fewer than 20 cases reported in world literature so far and only 1 previous case report describing the ultrasound findings. The Doppler findings of parotid Castleman''s disease have never been described before to the best of the authors'' knowledge. This report describes the ultrasonographic and Doppler findings in a histopathologically proven case of Castleman''s disease of the left parotid gland in a young man.     

Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy

Background  

Phagocytosis of apoptotic cells by macrophages induces a suppressor phenotype. Previous data from our group suggested that this occurs via Platelet-activating factor receptor (PAF-R)-mediated pathways. In the present study, we investigated the impact of apoptotic cell inoculation or induction by a chemotherapeutic agent (dacarbazine, DTIC) on tumour growth, microenvironmental parameters and survival, and the effect of treatment with a PAF-R antagonist (WEB2170). These studies were performed in murine tumours: Ehrlich Ascitis Tumour (EAT) and B16F10 melanoma.     

Insights into the molecular pathogenesis of progression in multiple sclerosis: potential implications for future therapies

Despite recent advances in the diagnosis and treatment of multiple sclerosis, we still lack a consensus regarding the causes, pathogenesis, and mechanisms of disease progression. Current evidence indicates that multiple sclerosis is an inflammatory neurodegenerative disorder in which both adaptive and innate immunity play important roles in initiation and maintenance of the disease. Recent evidence supports the notion of molecular pathologic abnormalities beyond the plaques and dysfunction of neurons in normal appearing areas, in addition to the multifocal demyelination and axonal loss, as important features that may underlie early reversible changes in the disease. Chronic failure of remyelination, axonal regeneration, and neuronal dysfunction may contribute to disease progression. This article discusses the emerging molecular evidence for the progression of multiple sclerosis with particular focus on alterations in the local central nervous system microenvironment of neural and glial cells. The molecular pathways leading to structural and functional neurodegeneration and those that prevent regeneration need to be identified in order to design new therapeutic strategies that can halt or even reverse disease progression.     

Evidence that fibrinogen γ′ directly interferes with protofibril growth: implications for fibrin structure and clot stiffness

Summary. Background: Fibrinogen contains an alternatively spliced γ‐chain (γ′), which mainly exists as a heterodimer with the common γA‐chain (γA/γ′). Fibrinogen γ′ has been reported to inhibit thrombin and modulate fibrin structure, but the underlying mechanisms are unknown. Objective: We aimed to investigate the molecular mechanism underpinning the influence of γ′ on fibrin polymerization, structure and viscoelasticity. Methods: γA/γA and γA/γ′ fibrinogens were separated using anion exchange chromatography. Cross‐linking was controlled with purified FXIIIa and a synthetic inhibitor. Fibrin polymerization was analyzed by turbidity and gel‐point time was measured using a coagulometer. We used atomic force microscopy (AFM) to image protofibril formation while final clot structure was assessed by confocal and scanning electron microscopy. Clot viscoelasticity was measured using a magnetic microrheometer. Results: γA/γ′ fibrin formed shorter oligomers by AFM than γA/γA, which in addition gelled earlier. γA/γ′ clots displayed a non‐homogenous arrangement of thin fibers compared with the uniform arrangements of thick fibers for γA/γA clots. These differences in clot structure were not due to thrombin inhibition as demonstrated in clots made with reptilase. Non‐cross‐linked γA/γA fibrin was approximately 2.7 × stiffer than γA/γ′. Cross‐linking by FXIIIa increased the stiffness of both fibrin variants; however, the difference in stiffness increased to approximately 4.6 × (γA/γA vs. γA/γ′). Conclusions: Fibrinogen γ′ is associated with the formation of mechanically weaker, non‐uniform clots composed of thin fibers. This is caused by direct disruption of protofibril formation by γ′.     

What is the value of ENT specialist outreach clinics?

Ear, nose and throat (ENT) specialist outreach clinics, in which hospital-based consultants hold clinics in general practice surgeries, have been popular with general practitioners (GPs) and patients. This prospective study recorded data on 1155 consecutive patients seen by one ENT surgeon in two GP surgeries. At each consultation, a record was kept of the requirement for further investigations that would normally be done at the same time as the consultation in a hospital department. The results showed that 76 per cent of patients needed an investigation, which would be readily available in a hospital but not in a GP surgery (audiometry, endoscopy, microscopy of the ear, a minor procedure or X-ray). This study indicates that despite the apparent convenience of outreach ENT clinics to patients and GPs, patients may need to spend more time being assessed than they would if they were investigated in one visit to a hospital department. Unless an outreach clinic is used frequently, it is difficult to justify the cost of equipping it to the same level as a hospital department. Limited resources would be better spent providing good access to well-equipped regularly-used hospital ENT outpatient departments.     

Modulation of sensitivity to mitoxantrone in human chronic myeloid leukemia cells by the antidepressant sintamil

The utility of mitoxantrone (MTN) in the cytotoxic chemotherapy of human chronic myeloid leukemia (CML) is envisaged. In the present study we employed marginally toxic concentration of MTN and the antidepressant sintamil (SNT) as drug response modulator to evaluate the heterogeneous response to chemotherapy by CML cells and to potentiate the cytotoxicity of MTN. In vitro results from 26 different CML blood samples displayed variation in cytotoxicity of MTN (1 microgram/ml) alone alone and in the resulting synergistic inhibition of DNA biosynthesis with the combination of SNT (10 micrograms/ml). Of the 26 samples studied, 14 samples indicated synergistic, 2 additive, and 11 less than additive cytotoxic effects due to the combined treatment with MTN and SNT. The cytotoxicity induced by MTN alone and the combination with SNT was found to be irreversible. Data suggest the utility of MTN alone and in combination with SNT in the treatment of CML and warrant further studies for the evaluation in the clinics.