Atorvastatin treatment is effective when used in combination with mefloquine in an experimental cerebral malaria murine model.

BACKGROUND: One of the major complications of Plasmodium falciparum infection is cerebral malaria (CM), which causes one million deaths worldwide each year, results in long-term neurological sequelae and the treatment for which is only partially effective. Statins are recognized to have an immunomodulatory action, attenuate sepsis and have a neuroprotective effect. Atorvastatin (AVA) has shown in vitro anti-malarial activity and has improved the activity of mefloquine (MQ) and quinine. METHODS: The efficiency of 40 mg/kg intraperitoneal AVA, alone or in association with MQ, was assessed in an experimental Plasmodium berghei ANKA rodent parasite model of CM and performed according to different therapeutic schemes. The effects on experimental CM were assessed through the evaluation of brain histopathological changes and neuronal apoptosis by TUNEL staining. RESULTS: AVA alone in the therapeutic scheme show no effect on survival, but the prophylactic scheme employing AVA associated with MQ, rather than MQ alone, led to a significant delay in mouse death and had an effect on the onset of CM symptoms and on the level of parasitaemia. Histopathological findings show a correlation between brain lesions and CM onset. A neuronal anti-apoptotic effect of AVA in the AVA + MQ combination was not shown. CONCLUSIONS: The combination of AVA and MQ therapy led to a significant delay in mouse mortality. There were differences in the incidence, time to cerebral malaria and the level of parasitaemia when the drug combination was administered to mice. When used in combination with MQ, AVA had a relevant effect on the in vivo growth inhibition and clinical outcome of P. berghei ANKA-infected mice.

Intestinal Necrosis Associated with Orally Administered Calcium Polystyrene Sulfonate Without Sorbitol.

OBJECTIVE: To describe a case of extensive intestinal necrosis with oral intake of calcium polystyrene sulfonate without sorbitol. CASE SUMMARY: A 73-year-old woman was admitted to the emergency department with abdominal pain. Abdominal computed tomography (CT) scan showed widespread dilatation of the bowel. The diagnosis of acute colonic pseudoobstruction was made. On day 3, her serum potassium level rose to 5.6 mEq/L. It was treated with hydrocortisone 100 mg/day and calcium polystyrene sulfonate 15 g/day via nasogastric tube from day 3 to day 6. On day 6, the severe abdominal pain recurred, with abdominal tenderness. CT scan showed pneumoperitoneum and peritoneal effusion. At surgery, 2 lenticular jejunal perforations and an ischemic cecum were found. Microscopic findings indicated that the transmural abscess contained massive inflammatory infiltrate and the cecal mucosa showed ulceration and inflammation with a fibrinous and purulent coating. Small gray-purple or blue angulated crystals were embedded in the cecal and most of the jejunal mucosal ulcers. On day 19, the patient died of multiple organ failure after her third laparotomy. DISCUSSION: Ion-exchanging resins are given orally or by retention enema for the treatment of hyperkalemia. The most commonly used and best-established resin is sodium polystyrene sulfonate. However, it is known to promote colonic necrosis when sorbitol is also given or especially in patients with renal failure or postoperative ileus. Calcium polystyrene sulfonate is another ion-exchange resin. There are few reports of adverse effects in the literature. Our case is interesting for 2 reasons: the resin given was calcium polystyrene sulfonate and sorbitol was not used. CONCLUSIONS: Like sodium polystyrene sulfonate, calcium polystyrene sulfonate is an ion-exchanging resin that can promote bowel necrosis. We believe that it should not be used with sorbitol or when bowel transit time is slowed.

Meningeal chondroblastic osteosarcoma: case report and review of the literature.

Primary meningeal osteosarcomas are exceedingly rare. We report a case of a 51-year-old man with a chondroblastic osteosarcoma treated with pre-operative embolization, surgical removal, followed by adjuvant chemotherapy and radiation therapy. Patient is alive without any recurrence 43 months after diagnosis.

Towards Understanding Therapeutic Failures in Masquelet Surgery: First Evidence that Defective Induced Membrane Properties are Associated with Clinical Failures.

The two-stage Masquelet induced-membrane technique (IMT) consists of cement spacer-driven membrane induction followed by an autologous cancellous bone implantation in this membrane to promote large bone defect repairs. For the first time, this study aims at correlating IMT failures with physiological alterations of the induced membrane (IM) in patients. For this purpose, we compared various histological, immunohistochemical and gene expression parameters obtained from IM collected in patients categorized lately as successfully (Responders; n = 8) or unsuccessfully (Non-responders; n = 3) treated with the Masquelet technique (6 month clinical and radiologic post-surgery follow-up). While angiogenesis or macrophage distribution pattern remained unmodified in non-responder IM as compared to responder IM, we evidenced an absence of mesenchymal stem cells and reduced density of fibroblast-like cells in non-responder IM. Furthermore, non-responder IM exhibited altered extracellular matrix (ECM) remodeling parameters such as a lower expression ratio of metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinases (TIMP-1) mRNA as well as an important collagen overexpression as shown by picrosirius red staining. In summary, this study is the first to report evidence that IMT failure can be related to defective IM properties while underlining the importance of ECM remodeling parameters, particularly the MMP-9/TIMP-1 gene expression ratio, as early predictive biomarkers of the IMT outcome regardless of the type of bone, fracture or patient characteristics.

Gas nuclei, their origin, and their role in bubble formation.

Gas bubbles are the primary agent in producing the pathogenic effects of decompression sickness. Bubble formation during decompression is not simply the consequence of inert gas supersaturation. Numerous experiments indicate that bubbles originate as pre-existing gas nuclei. Radii are on the order of 1 microm or less. Heterogeneous nucleation processes are involved in generating these gas entities. Musculoskeletal activity could be the main promoter of gas nuclei from stress-assisted nucleation. The half-life and faculty for nuclei to initiate bubble formation during decompression depend on many factors. Oxygen window and surface tension are involved in resolving bubbles. Two factors have been proposed to stabilize gas nuclei against dissolution: gas nuclei trapped in hydrophobic crevices and gas nuclei coated with surface-active molecules such as surfactants. Diffusion and surface tension could play an important role in the formation of gas nuclei crevices. However, while the concept of in vivo hydrophobic crevices remains a theoretical possibility, none have yet been identified in tissues and/or in microcapillaries. Moreover, while surfactants seem present in numerous tissues and could play a role in gas nuclei stabilization, they could also be involved in bubble elimination. The understanding of such mechanisms is of primary importance to neutralize nuclei and for modeling bubble growth. Here we present in a single document a summary of the original findings and views from authors in this field.

Malignant melanoma revealed by testicular metastasi.

We report the case of an 83 years old man supported for painless indurated and nodular lesion of the left testicle. Histological analysis identified a primary cutaneous melanoma metastasis although it has never been found on physical examination. The discovery of a testicular mass should suggest first a germ cell tumor, despite in some populations (age over 60 years), other diagnosis are more frequent, including metastasis. Due to rapid disease progression and high mortality rate within a short interval, a complete staging looking for other secondary locations must be done and a multidisciplinary care and palliative involvement must also be initiated in the context of metastatic melanoma.

Osteogenic Potential of Mesenchymal Stromal Cells Contributes to Primary Myelofibrosis.

Primary myelofibrosis is a myeloproliferative neoplasm that is a precursor to myeloid leukemia. Dysmegakaryopoiesis and extramedullary hematopoiesis characterize primary myelofibrosis, which is also associated with bone marrow stromal alterations marked by fibrosis, neoangiogenesis, and osteomyelosclerosis. In particular, contributions to primary myelofibrosis from mesenchymal stromal cells (MSC) have been suggested by mouse studies, but evidence in humans remains lacking. In this study, we show that bone marrow MSCs from primary myelofibrosis patients exhibit unique molecular and functional abnormalities distinct from other myeloproliferative neoplasms and these abnormalities are maintained stably ex vivo in the absence of leukemic cells. Primary myelofibrosis-MSC overexpressed heparin-binding cytokines, including proinflammatory TGFß1 and osteogenic BMP-2, as well as glycosaminoglycans such as heparan sulfate and chondroitin sulfate. Transcriptome and functional analyses revealed alterations in MSC differentiation characterized by an increased osteogenic potential and a TGFß1 signaling signature. Accordingly, phospho-Smad2 levels were intrinsically increased in primary myelofibrosis-MSC along with enhanced expression of the master bone regulator RUNX2, while inhibition of the endogenous TGFß1 receptor TGFßR1 impaired osteogenic differentiation in these MSCs. Taken together, our results define the source of a critical osteogenic function in primary myelofibrosis that supports its pathophysiology, suggesting that combined targeting of both the hematopoietic and stromal cell compartments in primary myelofibrosis patients may heighten therapeutic efficacy.

Osteochondrolipoma of the submandibular region: a case report and review of the literature.

Lipoma is an extremely common and ubiquitous benign soft tissue tumor composed of mature adipose tissue, with frequent differentiation towards other mesenchymal elements such as blood vessels, fibrous tissue, or muscle. They are typically slow-growing, encapsulated, superficial or deep, and have a wide range in size depending on their location. The presence of cartilage or bone is very rare, with most reported cases in the head and neck area. We report the case of an osteochondrolipoma of the submandibular region with associated benign bone marrow elements, with a review of the literature and discussion of the differential diagnosis.

Fulminant adult-onset subacute sclerosing panencephalitis: a case report.

We present the case of a young adult who developed acute encephalopathy with severe status epilepticus and rapid deterioration to vegetative state and death within 6 weeks. Although the clinical picture, MRI and EEG findings were atypical, the hypothesis of subacute sclerosing panencephalitis (SSPE) was suggested by markedly increased intrathecal IgG synthesis in the cerebrospinal fluid, and diagnosis was confirmed by the presence of high antimeasles antibodies in cerebrospinal fluid and brain biopsy findings. Acute SSPE is an exceptionally rare and little-known form of SSPE with protean symptomatology, and this case is to our knowledge the first observation of SSPE presenting with status epilepticus in adults. Our case reinforces the need to include, even in developed countries, SSPE as a diagnostic possibility in unexplained acute encephalopathies.