Modeling the response of a biofilm to silver-based antimicrobial.

Biofilms are found within the lungs of patients with chronic pulmonary infections, in particular patients with cystic fibrosis, and are the major cause of morbidity and mortality for these patients. The work presented here is part of a large interdisciplinary effort to develop an effective drug delivery system and treatment strategy to kill biofilms growing in the lung. The treatment strategy exploits silver-based antimicrobials, in particular, silver carbene complexes (SCC). This manuscript presents a mathematical model describing the growth of a biofilm and predicts the response of a biofilm to several basic treatment strategies. The continuum model is composed of a set of reaction-diffusion equations for the transport of soluble components (nutrient and antimicrobial), coupled to a set of reaction-advection equations for the particulate components (living, inert, and persister bacteria, extracellular polymeric substance, and void). We explore the efficacy of delivering SCC both in an aqueous solution and in biodegradable polymer nanoparticles. Minimum bactericidal concentration (MBC) levels of antimicrobial in both free and nanoparticle-encapsulated forms are estimated. Antimicrobial treatment demonstrates a biphasic killing phenomenon, where the active bacterial population is killed quickly followed by a slower killing rate, which indicates the presence of a persister population. Finally, our results suggest that a biofilm with a ready supply of nutrient throughout its depth has fewer persister bacteria and hence may be easier to treat than one with less nutrient.

Kaposi's sarcoma after long-acting steroids: time until remission and drug washout.

Long-acting steroids (LAS) are widely used to treat various inflammatory diseases and allergies. They have many adverse effects including the inhibition of the hypothalamopituitary axis that can last several months. LAS are also strong immunosuppressors and can result in severe opportunistic infections and immunodeficiency-related malignancies. However, the time needed for immune recovery after withdrawal of LAS is unknown. Here we report a case of Kaposi's sarcoma (KS) and severe immunosuppression after a chronic triamcinolone acetonide (TA) treatment. Six months after withdrawal, traces of TA were still detected in the serum by HPLC mass spectrometry. At 8 months, the drug became undetectable, and clinical and biological signs of immune recovery - beginning of KS regression, normalization of IgG levels and CD4 T lymphocyte counts - became noticeable. We then provide a review of the literature on the time until remission of KS after immunosuppression reduction. We also reviewed the cases of KS induced by TA, and the metabolic side effects of TA when compared to standard glucocorticoids.

[Cutaneous side effects of EGF receptor inhibitors]. / Manifestations cutanées associées aux inhibiteurs du récepteur de l'EGF.

EGFR receptor inhibitors are used for the treatment of a number of solid tumors. Their cutaneous toxicity is a specific and frequent side effect that has shown to be correlated to the antitumoral effect. Here, we present an overview of the cutaneous manifestations and management of EGF receptor inhibitors toxicity.

Fine-needle aspiration for the diagnosis of orbital hematolymphoid lesions.

Ocular and periocular hematolymphoid diseases are a diverse group of lesions affecting various soft tissue structures within the orbital cavity. Lymphoid proliferations in particular are among the most commonly diagnosed entities in orbital pathology. When noninvasive techniques fail to confirm or rule out the suspicion of orbital neoplasia, fine-needle aspiration (FNA) may be of use in establishing a diagnosis in a reliable, timely, cost-effective and safe manner. From 1986 to 1999, 79 orbital/ocular needle aspiration biopsies were conducted by staff ophthalmologists at Allegheny General Hospital. Slides from these cases and corresponding reports were pulled from the cytology files and grouped into the two broad categories of hematolymphoid and other. Specimens came from patients ranging in age from 14 to 88 years (mean, 64 years) with eight patients having known histories of hematolymphoid disorders. Immunocytochemical (ICC) studies were performed in 33% of the cases (14/43). Review of the diagnoses for the 79 aspiration specimens revealed 30 cases diagnosed as lymphoma/atypical lymphocytic infiltrate, cases diagnosed as inflammation or abscess, three cases diagnosed as plasmacytoma, three cases called suboptimal with scant inflammatory cells, and one case of Langerhans' cell histiocytosis. Hematolymphoid diagnoses accounted for 54% (43/79) of all diagnoses. Histologic correlation was available in 33% (14/43) of the cases (nine cases diagnosed as cytologically atypical/malignant and five cases called cytologically benign/suboptimal) with 100% correlation. Hematolymphoid lesions of the orbit are readily diagnosed by FNA. Because many hematolymphoid malignancies are treated as systemic or multiorgan system diseases and because ocular lymphomas may also involve the central nervous system, nonsurgical attempts at diagnosis have the potential to spare the patient procedural morbidity which may be associated with open biopsy. Our experience indicates that the combination of FNA, judicious use of immunocytochemical studies, and correlation with pertinent clinical information and imaging studies allows for reliable and effective classification and diagnosis of orbital hematolymphoid lesions.

Cytologic features useful for distinguishing small cell from non-small cell carcinoma in bronchial brush and wash specimens.

One blinded observer (C.D.S.) retrospectively reviewed 76 previously diagnosed and biopsy-confirmed malignant bronchial brush and wash specimens, 46 non-small cell and 30 small cell carcinomas, obtained from 55 patients. Each case was scored for the presence or absence of 36 standard criteria (architectural, cytoplasmic, and nuclear). Logistic regression analysis was used to determine which criteria were most useful for separating small cell from non-small cell lesions. Although no single criterion displayed 100% sensitivity and specificity for small cell cancer, univariate statistical analysis indicated that 3 individual criteria (nuclear molding, finely granular or "salt and pepper" chromatin, and scant delicate cytoplasm) were more than 90% sensitive and specific in cases of small cell carcinoma. The presence of nuclear molding alone provided the best fit for the logistic regression model. When nuclear molding was present, the odds of a small cell diagnosis increased more than 300-fold. Nuclear molding, finely granular or salt and pepper chromatin, and scant, delicate cytoplasm are the 3 most sensitive and specific cytomorphologic features traditionally used to separate small cell from non-small cell carcinoma. Nuclear molding alone represents the most significant cytomorphologic feature for distinguishing between these malignant lesions.