Micro-invasive vulvar Paget's disease and lymph node metastasis: a same disease?

Vulvar Paget's disease is sub-classified into three types based upon its origin. It might be a primary vulvar disease (type 1) or associated with a non-cutaneous adenocarcinoma-rectal, colonic, cervical (type 2) or linked with an urothelial neoplasia (type 3). Type 1lesions must be considered as potentially invasive. Their immunophenotype is CK7+/CK20-. Classically, in case of depth of invasion below 1mm, nodal metastases are exceptional. We report a case of type 1?Paget's disease in a postmenopausal woman with superficial invasion and multiple inguinal nodal metastases.     

Basaloid squamous carcinoma with a spindle cell component and osseous metaplasia presenting as a polyp of the hypopharynx

We report a case of basaloid squamous carcinoma with a spindle cell component of the hypopharynx, in a 61-years-old-man. An excisional biopsy of a pedonculated and polypoid tumour was performed by endoscopy. The histologic examination revealed a biphasic tumour with both a basaloid carcinomatous and a spindle cell component. Focally, osseous metaplasia was seen. The spindle cell component demonstrated immunoreactivity with the p63 epithelial marker. The patient was treated with chemotherapy followed by radiotherapy. The patient has been free of disease for one year. It's the ninth case reported in the literature of a biphasic carcinoma with both a basaloid squamous and a spindle cell component and the first case with osseous metaplasia.     

Bilateral tibial chronic osteomyelitis due to Pantoea agglomerans in a patient with sickle cell disease

A 20-yr-old Gabonese man with homozygous SS sickle cell diseaseand a mechanical aortic valve had leg pain, which was permanentfor 2 months. He was healthy and afebrile. A 4-cm abscess was     

A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis

Neuronal ceroid lipofuscinoses (NCLs) represent the most common group of inherited progressive encephalopathies in children. They are characterized by progressive loss of vision, mental and motor deterioration, epileptic seizures, and premature death. Rare adult forms of NCL with late onset are known as Kufs’ disease. Loci underlying these adult forms remain unknown due to the small number of patients and genetic heterogeneity. Here we confirm that a late-onset form of NCL recessively segregates in US and French pedigrees of American Staffordshire Terrier (AST) dogs. Through combined association, linkage, and haplotype analyses, we mapped the disease locus to a single region of canine chromosome 9. We eventually identified a worldwide breed-specific variant in exon 2 of the Arylsulfatase G (ARSG) gene, which causes a p.R99H substitution in the vicinity of the catalytic domain of the enzyme. In transfected cells or leukocytes from affected dogs, the missense change leads to a 75% decrease in sulfatase activity, providing a functional confirmation that the variant might be the NCL-causing mutation. Our results uncover a protein involved in neuronal homeostasis, identify a family of candidate genes to be screened in patients with Kufs'' disease, and suggest that a deficiency in sulfatase is part of the NCL pathogenesis.     

Flavocoxid,a dual inhibitor of cyclooxygenase and 5-lipoxygenase,blunts pro-inflammatory phenotype activation in endotoxin-stimulated macrophages

Background and purpose:

The flavonoids, baicalin and catechin, from Scutellaria baicalensis and Acacia catechu, respectively, have been used for various clinical applications. Flavocoxid is a mixed extract containing baicalin and catechin, and acts as a dual inhibitor of cyclooxygenase (COX) and 5-lipoxygenase (LOX) enzymes. The anti-inflammatory activity, measured by protein and gene expression of inflammatory markers, of flavocoxid in rat peritoneal macrophages stimulated with Salmonella enteritidis lipopolysaccharide (LPS) was investigated.

Experimental approach:

LPS-stimulated (1 µg·mL⁻¹) peritoneal rat macrophages were co-incubated with different concentrations of flavocoxid (32–128 µg·mL⁻¹) or RPMI medium for different incubation times. Inducible COX-2, 5-LOX, inducible nitric oxide synthase (iNOS) and inhibitory protein κB-α (IκB-α) levels were evaluated by Western blot analysis. Nuclear factor κB (NF-κB) binding activity was investigated by electrophoretic mobility shift assay. Tumour necrosis factor-α (TNF-α) gene and protein expression were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay respectively. Finally, malondialdehyde (MDA) and nitrite levels in macrophage supernatants were evaluated.

Key results:

LPS stimulation induced a pro-inflammatory phenotype in rat peritoneal macrophages. Flavocoxid (128 µg·mL⁻¹) significantly inhibited COX-2 (LPS = 18 ± 2.1; flavocoxid = 3.8 ± 0.9 integrated intensity), 5-LOX (LPS = 20 ± 3.8; flavocoxid = 3.1 ± 0.8 integrated intensity) and iNOS expression (LPS = 15 ± 1.1; flavocoxid = 4.1 ± 0.4 integrated intensity), but did not modify COX-1 expression. PGE₂ and LTB₄ levels in culture supernatants were consequently decreased. Flavocoxid also prevented the loss of IκB-α protein (LPS = 1.9 ± 0.2; flavocoxid = 7.2 ± 1.6 integrated intensity), blunted increased NF-κB binding activity (LPS = 9.2 ± 2; flavocoxid = 2.4 ± 0.7 integrated intensity) and the enhanced TNF-α mRNA levels (LPS = 8 ± 0.9; flavocoxid = 1.9 ± 0.8 n-fold/β-actin) induced by LPS. Finally, flavocoxid decreased MDA, TNF and nitrite levels from LPS-stimulated macrophages.

Conclusion and implications:

Flavocoxid might be useful as a potential anti-inflammatory agent, acting at the level of gene and protein expression.     

The clinical significance of Candida colonization of respiratory tract secretions in critically ill patients

PURPOSE: Clinical uncertainty exists regarding the significance of colonization confined to respiratory tract secretions with Candida sp in critically ill patients. Our objectives were to describe such colonization, its associated risk factors, and to examine the clinical outcomes in patients with a clinical suspicion of ventilator-associated pneumonia with isolated Candida colonization compared to those without. MATERIALS AND METHODS: In a retrospective analysis of the Canadian ventilator-associated pneumonia study, patients were divided into 2 groups according to the isolated presence or absence of Candida in the respiratory tract enrollment culture. We compared length of mechanical ventilation, intensive care unit and hospital stay, and mortality outcomes between groups. We used multiple logistic regression analysis to determine factors independently associated with Candida colonization and hospital mortality. RESULTS: Of the 639 eligible patients, 114 (17.8%) were colonized with Candida in the enrollment culture. A multivariate analysis identified female sex (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.02-2.65), number of comorbidities (OR, 1.35; 95% CI, 1.08-1.71), worsening or persistent infiltrate at randomization (OR, 1.92; 95% CI, 1.09-1.38), antibiotics started within 3 days of randomization (OR, 3.16; 95% CI, 1.71-5.83), and on antibiotics at randomization but all started more than 3 days before randomization (OR, 3.04; 95% CI, 1.68-5.50) as variables associated with Candida respiratory tract colonization. A significant increase in median hospital stay (59.9 vs 38.6 days, P = .006) and hospital mortality (34.2% vs 21.0%, P = .003) was observed in patients with Candida colonization. In a multivariate model, Candida colonization of the respiratory tract was independently associated with hospital mortality (OR, 2.47; 95% CI, 1.39-4.37). CONCLUSION: Respiratory tract Candida colonization is associated with worse clinical outcomes and is independently associated with increased hospital mortality. However, it is unclear whether Candida colonization is causally related to poor outcomes or whether it is a marker for increased morbidity and mortality.     

Role of Endothelium/Nitric Oxide and Cyclic AMP in Isoproterenol Potentiation of 17ß-Estradiol-Mediated Vasorelaxation

Background: Calcitonin gene-related peptide (CGRP) is known to have an extremely potent and prolonged vasodilator effect on the coronary arteries. Studies have shown that CGRP increased coronary blood flow and alleviated reperfusion injury in vitro. It is still unknown, however, whether exogenous CGRP has a protective effect on the reperfusion heart associated with cardiopulmonary bypass (CPB). Methods: An in vivo porcine model of CPB was established. Twenty pigs, 10 controls and 10 CGRP used animals (CGRP group), were performed a median sternotomy followed by a standard CPB. All the hearts were arrested for 45 minutes. In the CGRP group, 1mg/kg CGRP was added into the cardioplegia, and another 1mg/kg was reperfused just before the aortic cross-clamp was removed. In both groups, myocardial microvascular perfusion, coronary arterial microvessel diameter and microvessel blood flow were detected by a laser doppler flowmeter and a contact microscope with TV monitor on five consecutive time perioperatively. Result: Myocardial microvascular perfusion was significantly higher and coronary arterial microvessel diameter was larger in the CGRP group on every point of time of reperfusion compared to those in the control group. In the CGRP group, microvessel blood flow also improved significantly than that in the control group during reperfusion. Conclusion: CGRP improves myocardial microcirculation during cardiac ischemia-reperfusion associated with CPB and could become a new, potent myocardial protector.