Hennekam lymphangiectasia syndrome

Hennekam lymphangiectasia syndrome is a rare autosomal recessive condition. Onset is usually in childhood. The prevalence is unknown but less than 50 cases have been reported in the literature. Incidence is about 1 in 100000 and occurs in all ethnic groups. The syndrome is characterized by the association of lymphedema, intestinal lymphangiectasia, intellectual deficit and facial dysmorphism. Here is a case presented with distension of abdomen with ascites, bilateral pedal oedema, macrocephaly, left half facial edema, left half hypertrophied tongue, dental anomalies, acanthosis nigricans, acrochordons and syndactyly consistent with a diagnosis of Hennekam syndrome. The diagnosis of Hennekam is suspected on the basis of clinical phenotypic features. This is one of the very few cases reported from India

Myopericarditis and Pericardial Effusion as the Initial Presentation of Systemic Lupus Erythematosus

Myopericarditis with a pericardial effusion as the initial presenting feature of SLE is uncommon. We report an unusual case of myopericarditis and pericardial effusion with subsequent heart failure, as the initial manifestation of SLE. The timely recognition and early steroid administration are imperative in SLE-related myopericarditis with cardiomyopathy to prevent the mortality associated with this condition

Incidence, severity, prognostic significance of thrombocytopenia in malaria

Background: Malaria is an infectious disease caused by plasmodium parasite. P. falciparum account for majority of morbidity and mortality. Thrombocytopenia and anaemia are the most frequently associated hematological complications in malaria. The low platelet count together with acute febrile syndrome emerged as the strongest predictor of malaria a finding that is frequent and present even before anemia and splenomegaly sets in. Severe thrombocytopenia is a good predictor of poor prognosis than mild and moderate thrombocytopenia. The aim is to study the incidence, severity, prognostic significance of thrombocytopenia in malaria.Methods: This was an observational and prospective study. The study enrolled 100 patients with thrombocytopenia and fever who were proven to have malaria either by peripheral smear or Quantitative Buffy Coat (QBC) test or malarial antigen assay were included in the study and patients with thrombocytopenia due to other causes were excluded from the study. Platelet count was estimated on a fully automated quantitative analyzer. All the 100 patients were followed during the hospital stay and upto discharge or till the outcome.  Results: The incidence of thrombocytopenia was 73% indicating a common association in malaria. Complicated malaria was observed in 58.80% of P. falciparum infection whereas 66% of P. vivax infection was associated with uncomplicated malaria. Severe thrombocytopenia showed positive correlation with severity of malaria. Thrombocytopenic patients with effective anti-malarial treatment showed 95.90% recovery and 3 patients 4.10% had mortality. Patients with severe thrombocytopenia were 8.5 times more likely to have complicated malaria with P <0.001 according to student ‘t’ test.  Conclusion: Thrombocytopenia is the most common hematological finding in malaria. Severe thrombocytopenia showed positive correlation with complicated malaria and a good predictor of poor prognosis. Patients with classical malarial fever and thrombocytopenia who were negative for malaria parasite were not included in the study.

Synergistic effect of scaffold composition and dynamic culturing environment in multi-layered systems for bone tissue engineering

Bone extracellular matrix (ECM) is composed of mineralized collagen fibrils which support biological apatite nucleation that participates in bone outstanding properties. Understanding and mimicking bone morphological and physiological parameters at a biological scale is a major challenge in tissue engineering scaffolding. Using emergent (nano)technologies scaffold designing may be critically improved, enabling highly functional tissue substitutes for bone applications. This study aims to develop novel biodegradable composite scaffolds of tricalcium phosphate (TCPs) and electrospun nanofibers of poly(e-caprolactone) (PCL), combining TCPs osteoconductivity with PCL biocompatibility and elasticity, mimicking bone structure and composition. We hypothesized that scaffolds with such structure/composition would stimulate the proliferation and differentiation of bone marrow stromal cells (BMSCs) towards the osteogenic phenotype. Composite scaffolds, developed by electrospining using consecutive stacked layers of PCL and TCPs, were characterized by FTIR spectroscopy, X-Ray diffraction and scanning electronic microscopy. Cellular behavior was assessed in goat BMSCs seeded onto composite scaffolds and cultured in static or dynamic conditions, using basal or osteogenic media during 7, 14 or 21 days. Cellular proliferation was quantified and osteogenic differentiation confirmed by alkaline phosphatase activity, alizarin red staining and immunocytochemistry for osteocalcin and collagen I. Results suggest that PCL-TCP scaffolds provide a 3D support for gBMSCs proliferation and osteogenic differentiation with production of ECM. TCPs positively stimulate the osteogenic process, especially under dynamic conditions, where PCL-TCP scaffolds are sufficient to promote osteogenic differentiation even in basal medium conditions. The enhancement of the osteogenic potential in dynamic conditions evidences the synergistic effect of scaffold composition and dynamic stimulation in gBMSCs osteogenic differentiation.Fundação para a Ciência e a Tecnologia (FCT)European NoE EXPERTISSUES (NMP3-CT- 2004-500283

Multi-stimuli-responsive Self-immolative Polymer Assemblies

Self-immolative polymers (SIPs) undergo depolymerization in response to the cleavage of stimuli-responsive end-caps from their termini. Some classes of SIPs, including polycarbamates, have depolymerization rates that depend on environmental factors such as solvent and pH. In previous work, hydrophobic SIPs have been incorporated into amphiphilic block copolymers and used to prepare nanoassemblies. However, stimuli-responsive hydrophilic blocks have not previously been incorporated. In the current work, we synthesized amphiphilic copolymers composed of a hydrophobic polycarbamate SIP block and a hydrophilic poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) block connected by a UV light-responsive linker end-cap. It was hypothesized that after assembly of the block copolymers into nanoparticles, chain collapse of the PDMAEMA above its lower critical solution temperature (LCST) might change the environment of the SIP block, thereby altering its depolymerization rate. Self-assembly of the block copolymers was performed, and the depolymerization of the resulting assemblies was studied by fluorescence spectroscopy, dynamic light scattering, and NMR spectroscopy. At 20 °C, the system exhibited a selective response to the UV light. At 65 °C, above the LCST of PDMAEMA, the systems underwent more rapid depolymerization, suggesting that the increase in rate arising from the higher temperature dominated over environmental effects arising from chain collapse

The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation

Although targeted therapies are often effective systemically, they fail to adequately control brain metastases. In preclinical models of breast cancer that faithfully recapitulate the disparate clinical responses in these microenvironments, we observed that brain metastases evade phosphatidylinositide 3-kinase (PI3K) inhibition despite drug accumulation in the brain lesions. In comparison to extracranial disease, we observed increased HER3 expression and phosphorylation in brain lesions. HER3 blockade overcame the resistance of HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases to PI3K inhibitors, resulting in marked tumor growth delay and improvement in mouse survival. These data provide a mechanistic basis for therapeutic resistance in the brain microenvironment and identify translatable treatment strategies for HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases

The Artelon CMC spacer compared with tendon interposition arthroplasty: A randomized, controlled, multicenter study of 109 patients with osteoarthritis followed for 1 year

Background and purpose The Artelon CMC spacer is designed for surgical treatment of osteoarthritis (OA) in the carpometacarpal joint of the thumb (CMC-I). Good results using this degradable device were previously presented in a pilot study. We now present results from a larger randomized, controlled, multicenter study