Current treatment approaches to early childhood medulloblastoma.

Treatment of medulloblastoma, the most common malignant brain tumor of childhood, is particularly challenging in very young children, owing to the increased susceptibility of the immature brain to treatment-induced neurocognitive deficits. Three promising strategies have been developed in combination with systemic postoperative chemotherapy, to avoid craniospinal irradiation for young children with nonmetastatic medulloblastoma, these include: high-dose chemotherapy, with and without local radiotherapy; intraventricular chemotherapy; and local radiotherapy. More intensified strategies may be required for metastatic medulloblastoma.

Natural IgM antibodies: the orphaned molecules in immune surveillance.

Natural IgM antibodies are typical victims of prejudices which originated in the mid 80 s. Over the years, these molecules were considered as the pariahs among the immune competent molecules and their characteristic properties, like low affinity, cross-reactivity and pentameric structure, were assessed as useless, difficult, nebulous, etc. Today, mainly based on a few scientists' persistent work and the key discoveries on innate immune recognition, natural IgM antibodies are "back on stage".

Freeze-thawing of breast milk does not prevent cytomegalovirus transmission to a preterm infant.

Freezing human milk is recommended to inactivate cytomegalovirus (CMV). A case of a preterm infant exclusively receiving frozen breast milk from his CMV seropositive mother showed that storage of breast milk for two months at -20 degrees C did not prevent symptomatic postnatal CMV infection.

Role of immune cells in animal models for inherited peripheral neuropathies.

Mice expressing half of the normal dose of protein zero (P0+/- mice) or completely deficient gap-junction protein connexin 32 -/- mice mimic demyelinating forms of inherited neuropathies, such as Charcot-Marie-Tooth (CMT) neuropathies type 1B and CMT type 1X, respectively. In both models, an almost normal myelin formation is observed during the first months of life, followed by a slowly progressing demyelinating neuropathy. In both models, there is a substantial increase of CD8+ T-lymphocytes and macrophages within the demyelinating nerves.

Inflammation and bronchopulmonary dysplasia: a continuing story.

Increasing evidence indicates that bronchopulmonary dysplasia (BPD) results, at least in part, from an imbalance between pro-inflammatory and anti-inflammatory mechanisms, with a persistent imbalance that favours pro-inflammatory mechanisms. The inflammatory response is characterised by an accumulation of neutrophils and macrophages in the airways and pulmonary tissue of preterm infants and, moreover, by an arsenal of pro-inflammatory mediators which affect the alveolar capillary unit and tissue integrity. As well as pro-inflammatory cytokines and toxic oxygen radicals, various lipid mediators as well as potent proteases may be responsible for acute lung injury.

High efficiency transfection of glioma cell lines and primary cells for overexpression and RNAi experiments.

In order to investigate the impact of signalling proteins on the phenotype and malignant behavior of glioblastoma cells, we optimized the transfection procedure of human glioblastoma cell lines U251, U373, GaMG and of primary cells obtained from a patient's tumor using nucleofection technology in conjunction with plasmid pmaxGFP. We describe the optimization procedure, show that a high percentage of the cells can be transfected and that nucleofection does not cause phenotypic alterations of the cells. Therefore, we conclude that nucleofection is a highly efficient tool to deliver plasmids for transient protein overexpression and siRNA for specific protein knock-down to different glioblastoma cell lines or primary cells.

Clinical review: Adrenocortical carcinoma: clinical update.

Context: Adrenocortical carcinoma (ACC) is a rare and heterogeneous malignancy with incompletely understood pathogenesis and poor prognosis. Patients present with hormone excess (e.g.

Attenuated demyelination in the absence of the macrophage-restricted adhesion molecule sialoadhesin (Siglec-1) in mice heterozygously deficient in P0.

Mouse mutants heterozygously deficient for the myelin component P0 mimic some forms of inherited neuropathies in humans. We have previously shown that both T lymphocytes and macrophages contribute to the demyelinating neuropathy. Both cell types appear to influence each other mutually, i.

Neurodegeneration and clinical relevance for early treatment in multiple sclerosis.

The treatment of MS with immunomodulatory agents such as interferon beta and glatiramer acetate, early in the disease course, is increasingly recognized as benefiting patient outcome. MS is a chronic inflammatory disease of the central nervous system with morphological hallmarks of inflammation, demyelination, axonal loss and gliosis. While inflammation and demyelination induce neurological deficit, which is at least partly reversible, axonal loss beyond the threshold of compensation is always accompanied by irreversible clinical disease progression.

Progression of heart failure in right univentricular pacing compared to biventricular pacing.

Background: Cardiac resynchronization therapy (CRT) improves hemodynamics and symptoms of heart failure by reducing ventricular dyssynchronity. Conversely, recent studies have demonstrated that right univentricular pacing in patients with an ejection fraction below 40% aggravates heart failure. In this retrospective study, we compared progression of disease in patients with mild to moderate heart failure that were treated with a right univentricular pacing device and patients with congestive heart failure that were treated with a biventricular system.

Management of adrenal insufficiency in different clinical settings.

Adrenal insufficiency is a rare disease, but its prevalence is increasing. The most frequent cause of primary adrenal insufficiency in western countries is autoimmune adrenalitis, whereas secondary adrenal insufficiency is most often caused by pituitary tumours and their treatment (e.g.

Glucose requirement for hypoxic accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha).

Hypoxia-inducible factor-1alpha (HIF-1alpha) is both a potential endogenous marker of tumor hypoxia and therapeutic target, and elevated HIF-1alpha protein levels have been shown to be associated with increased hypoxic radiation resistance in FaDu human pharyngeal carcinoma cells in vitro. Here, we found that in FaDu xenografts, no significant HIF-1alpha protein accumulation was detectable by either flow cytometry or Western blot, despite the presence of hypoxic (pimonidazole-positive, radiation resistant) cells. To investigate the effect of different tumor microenvironment conditions on hypoxic HIF-1alpha accumulation, we performed in vitro hypoxia experiments (0.

Tumor stroma-associated antigens for anti-cancer immunotherapy.

Immunotherapy has been widely investigated for its potential use in cancer therapy and it becomes more and more apparent that the selection of target antigens is essential for its efficacy. Indeed, limited clinical efficacy is partly due to immune evasion mechanisms of neoplastic cells, e.g.

Subcutaneous interferon-beta injections in patients with multiple sclerosis initiate inflammatory skin reactions by local chemokine induction.

Subcutaneous Interferon-beta (IFN-beta) injections for the treatment of multiple sclerosis (MS) frequently cause inflammatory injection site reactions. To study the role of chemokines we obtained skin biopsies from 7 MS patients 24 h after injection. At the IFN-beta but not at the contralateral placebo injection sites, we observed strong IP-10/CXCL10 and moderate MCP-1/CCL2 expression associated with extensive perivascular, highly CXCR3-positive T cell and macrophage infiltrates.

The estrogen receptor-alpha agonist 16alpha-LE2 inhibits cardiac hypertrophy and improves hemodynamic function in estrogen-deficient spontaneously hypertensive rats.

Objective: Cardiac mass increases with age and with declining estradiol serum levels in postmenopausal women. Although the non-selective estrogen receptor-alpha and -beta agonist 17beta-estradiol attenuates cardiac hypertrophy in animal models and in observational studies, it remains unknown whether activation of a specific estrogen receptor subtype (ERalpha or ERbeta) might give similar or divergent results. Therefore, we analyzed myocardial hypertrophy as well as cardiac function and gene expression in ovariectomized, spontaneously hypertensive rats (SHR) treated with the subtype-selective ERalpha agonist 16alpha-LE2 or 17beta-estradiol.

Congenital brachydactyly and nail hypoplasia: clue to bone-dependent nail formation.

Congenital hyponychia and anonychia are rare malformations which may form part of syndromes such as nail-patella syndrome, ectodermal dysplasias and brachydactylies, or may occur as an isolated finding. Congenital hyponychia and anonychia are frequently accompanied by underlying skeletal abnormalities. A 20-year-old woman showed congenital bilateral hypoplasia or aplasia of the second, third and fourth toenails with corresponding phalanx dysplasia or aplasia of the affected toes.

Mitotane for adrenocortical carcinoma treatment.

Adrenocortical carcinoma (ACC) is a rare neoplasm with poor prognosis. Mitotane is the only adrenal-specific agent available for the treatment of ACC, and although it has been used for several decades, many of its pharmacological properties, as well as its exact mechanism of action, remain to be fully elucidated. It is known that metabolic activation is essential for the adrenolytic activity of mitotane.

Single or combined oblique muscle surgery in acquired and congenital superior oblique palsy.

Oblique muscle surgery with weakening of the inferior oblique muscle alone or in combination with a tuck of the superior oblique tendon reduces in a dose-dependent relationship the vertical deviation in patients with an acquired or congenital superior oblique palsy. Reduction of cyclotropia and the V-sign is less dose dependent.

rhTSH-aided radioiodine ablation and treatment of differentiated thyroid carcinoma: a comprehensive review.

Traditionally, withdrawal of thyroid hormone has been used to attain the increase in serum TSH concentrations that are believed to optimize the trapping and retention of radioiodine for diagnostic procedures, thyroid remnant ablation and treatment of patients with differentiated thyroid cancer (DTC). However, withdrawal frequently causes clinical hypothyroidism, with resultant cognitive impairment, emotional dysfunction, physical discomfort, health risks in patients who are elderly, frail or have concomitant illness, and impaired quality of life and ability to work. Recombinant human TSH (rhTSH) was developed to provide TSH stimulation without withdrawal of thyroid hormone and the associated morbidity.

Osteomyelitis and skin ulcers caused by Mycobacterium szulgai in an AIDS patient.

Mycobacterium szulgai is a ubiquitious non-tuberculous mycobacterium causing infection in immunocompetent and immunocompromized patients. Clinically mimicking pulmonary tuberculosis in most cases described, rarely other manifestations occur. Here we report the case of an AIDS patient with osteomyelitis of the hand and toe, accompanied by multiple cutaneous ulcers of the chest and forearm.

Metastatic signet ring cell gastric carcinoma presenting as an infrarenal aortic aneurysm.

Metastases to liver, lungs, bone, and adrenal glands are common events in advanced gastric carcinoma. Occasionally, metastases to other parts of the body, such as the prostate gland [1] the gluteal muscle [2], or the cervix [3] are described. However, these are rare events in the natural history of the disease.

No influence of the P-glycoprotein polymorphisms MDR1 G2677T/A and C3435T on the virological and immunological response in treatment naïve HIV-positive patients.

Background: In a retrospective study of HIV-infected patients, we investigated the influence of the MDR1 genotype (G2677T/A and C3435T) on the virological and immunological response of treatment naive patients.

Methods: The MDR1 genotype was analysed from 72 patients in whom antiretroviral therapy was initiated between 1998 and 2004. Data were obtained at week 4, 12, 24 and 48 and were analysed by the Kruskal-Wallis test.