Four cancer cases after esophageal atresia repair: Time to start screening the upper gastrointestinal tract

Esophageal atresia(EA) is one of the most common congenital digestive malformations and requires surgical correction early in life. Dedicated centers have reported survival rates up to 95%. The most frequent comorbidities after EA repair are dysphagia(72%) and gastroesophageal reflux(GER)(67%). Chronic GER after EA repair might lead to mucosal damage, esophageal stricturing, Barrett's esophagus and eventually esophageal adenocarcinoma. Several long-term follow-up studies found an increased risk of Barrett's esophagus and esophageal carcinoma in EA patients, both at a relatively young age. Given these findings, the recent ESPGHAN-NASPGHAN guideline recommends routine endoscopy in adults born with EA. We report a series of four EA patients who developed a carcinoma of the gastrointestinal tract: three esophageal carcinoma and one colorectal carcinoma in a colonic interposition. These cases emphasize the importance of lifelong screening of the upper gastrointestinal tract in EA patients.     

Systemic human Netrin-1 gene delivery by adeno-associated virus type 8 alters leukocyte accumulation and atherogenesis in vivo

Atherosclerosis is an inflammatory disorder of arteries. Atherosclerotic plaque, in its early to intermediate stages, is composed largely of lipid-engorged foam cells. These foam cells are derived from the trafficking of monocytes (Mo) into the arterial intima, attracted to the site by chemoattractants. Given that foam cells are derived from the trafficking of Mo, the use of Netrin-1, an Mo chemorepellent, may be useful in limiting Mo accumulation and subsequent plaque formation. To investigate the potential of Netrin-1 for limiting atherosclerosis, we systemically delivered its human (h) cDNA by adeno-associated virus type 8 (AAV8, single-stranded structure) delivery into low-density lipoprotein receptor knockout (LDLR-/-) mice and placed the animals on a high cholesterol diet (HCD). Compared with control neomycin resistance (Neo) gene delivery/HCD, hNetrin-1 delivery resulted in a significant reduction in plaque formation, as determined by larger aortic lumen size, thinner intima-media thickness and lower blood velocity than the Neo/HCD control (all statistically significant). Indices of monocyte/macrophage (Mo/MΦ) accumulation, CD68, integrin, alpha M (ITGAM) and egf-like module containing, mucin-like, hormone receptor-like 1 (EMR-1), were reduced in hNetrin-1/HCD-treated animal's aortas and spleens compared with Neo/HCD-treated animals. Unexpectedly, CD25 and foxp3 (regulatory T cells (Tregs)) in the aorta were strongly upregulated. This is the first time the Mo/MΦ chemorepellent approach, and specific Netrin-1 gene delivery, has been performed for the reduction of Mo/MΦ burden and atherosclerosis. In addition, Netrin-1 has never before been linked to altered Treg levels. These data strongly suggest that hNetrin-1 gene delivery can reduce Mo/MΦ accumulation, inflammation and subsequent plaque formation.     

Aetiological factors for oral manifestations of HIV

OBJECTIVES: Describe the oral diseases in HIV-infected individuals in London, UK and identify social and medical factors related to the presence of specific oral diseases.
DESIGN: Cross-sectional analytic study.
SETTING: Dental clinics.
SUBJECTS: Consecutive sample of 456 patients with HIV infection.
METHODS: Social and medical history and clinical examinations. Univariate and logistic regression analysis.
OUTCOMES: Presence of HIV-associated oral disease.
RESULTS: 80% of patients with AIDS and 50% of patients with HIV had a specific oral disease. The most common diseases were hairy leukoplakia (30%), erythematous candidiasis (24%), pseudomembranous candidiasis (14%), angular chielitis (6%), necrotising periodontal disease (8%) and non-recurrent ulceration (6%).
CONCLUSIONS: The presence of erythematous candidiasis was not related to advanced HIV disease. Pseudomembranous candidiasis, hairy leukoplakia and mucosal ulceration were significantly associated with advanced HIV disease. Smoking was also identified as a strong aetiological factor in oral diseases. Longitudinal studies are required to further explore the prognostic significance of oral diseases in HIV infection.     

Calcinosis cutis following contact with calcium chloride solution

Calcinosis cutis is the deposition of insoluble calcium in the cutaneous tissue. Calcinosis cutis can be classified as metastatic, dystrophic, idiopathic or exogenous. We report a 48‐year‐old white man who was dismantling a portable ice skating rink when calcium chloride solution from the pipes spilt onto his clothing. Several days later, he started to develop mildly pruritic erythematous papules, some studded with white deposits and some with umbilication over the exposed areas corresponding to the spillage of the calcium chloride solution. Histological features revealed interstitial fibrohistiocytic reaction with calcium‐encrusted degenerated collagen bundles in the dermis which was further confirmed by von Kossa stain. He was commenced on topical corticosteroid cream twice daily and the lesions cleared completely between 6 to 10 weeks.     

Papillomavirus Microbicidal Activities of High-Molecular-Weight Cellulose Sulfate, Dextran Sulfate, and Polystyrene Sulfonate

The high-molecular-weight sulfated or sulfonated polysaccharides or polymers cellulose sulfate, dextran sulfate, and polystyrene sulfonate were tested for microbicidal activity against bovine papillomavirus type 1 (BPV-1) and human papillomavirus type 11 (HPV-11) and type 40 (HPV-40). In vitro assays included the BPV-1-induced focus-forming assay and transient infection of human A431 cells with HPVs. The compounds were tested for microbicidal activity directly by preincubation with virus prior to addition to cell cultures and indirectly by addition of virus to compound-treated cells and to virus-coated cells to test inactivation of the virus after virus-cell binding. The data indicated that all three compounds showed direct microbicidal activity with 50% effective concentrations between 10 to 100 microg/ml. These concentrations were nontoxic to cell cultures for both assays. When a clone of C127 cells was tested for microbicidal activity, approximately 10-fold-less compound was required to achieve a 50% reduction in BPV-1-induced foci than for the uncloned parental C127 cells. Pretreatment of cells with compound prior to addition of virus also demonstrated strong microbicidal activity with dextran sulfate and polystyrene sulfonate, but cellulose sulfate required several orders of magnitude more compound for virus inactivation. Polystyrene sulfonate prevented subsequent infection of HPV-11 after virus-cell binding, and this inactivation was observed up to 4 h after addition of virus. These data indicate that the polysulfated and polysulfonated compounds may be useful nontoxic microbicidal compounds that are active against a variety of sexually transmitted disease agents including papillomaviruses.     

Experimental results and related clinical implications of PET detection of epidermal growth factor receptor (EGFr) in cancer

The epidermal growth factor receptor (EGFr) is one of the most studied molecules as a target for cancer therapy. Over these last few years, several studies attempting to identify predictive biomarkers of treatment response, such as the receptor status or other molecules related to the downstream signalling pathway, have been conducted. However, from a clinical point of view, the information obtained from ex vivo analyses still has various limitations that may be overcome by the combination with molecular imaging technologies which may provide a noninvasive, global, in vivo evaluation of the molecular tumour background. The aim of this review is to report the preclinical results of all positron emission tomography (PET) tracers synthesized until now for in vivo detection of EGFr in cancer. Two classes of PET compounds have been developed: labelled small molecules such as tyrosine kinase inhibitors and labelled monoclonal antibodies. The in vitro and in vivo results of these PET tracers are very different depending on the chemical properties, positron emission radionuclide, or animal models. As a consequence, various critical questions are still open, and the implications of a translation in the clinical setting for EGFr imaging in cancer patients is discussed.     

Experimental Lead Neuropathy: Ultrastructural And Molecular Changes In The Rat Sciatic Nerve

Experimental lead intoxication is an important model for the study of cellular and molecular mechanisms of segmental demyelination in peripheral nerve. In this report we have compared pathological changes with the molecular and immunohistochemical expression of the proteins of compact and non-compact myelin in the demyelinating neuropathy induced in Sprague-Dawley rats after chronic administration (3 and 6 months) of lead acetate in drinking water. All the rats underwent the neurophysiological determination of the conduction velocity in the tail nerve at baseline and 3, 4.5 and 6 months after the beginning of the lead acetate administration. At the end of the treatment period the rats were sacrificed and sciatic nerve specimens were obtained. The neurophysiological study demonstrated a significant decrease in the nerve conduction velocity, which was already evident at the first determination (3 months) and persisted along the entire experiment. The neurophysiological results were in agreement with the pathological observations performed in the sciatic nerve, where several large demyelinated fibers were observed in the lead-intoxicated rats. Northern and Western blot analysis demonstrated that steady state mRNA and protein levels for P0, MBP, PMP22 and PLP were not changed comparing treated and control rats. Immunohistochemistry on teased fibers revealed that those proteins were distributed in areas of compact myelin along the internodes. In control fibers, as expected, MAG was found in the periaxonal cytoplasm, at nodes of Ranvier, and in the Schmidt-Lanterman incisures. In lead neuropathy, MAG was still limited to discrete regions, but the intensity of staining was reduced, in accordance with changes of paranodal structures. Immunohistochemical localization of other proteins of non-compacted myelin, including connexin-32, E-cadherin and β-catenin was also examined. Our data further suggest that chronic lead intoxication in the rat produces segmental demyelination due primarily to Schwann cell dysfunction.