Long-term add-on therapy (compassionate use) with oral artesunate in patients with metastatic breast cancer after participating in a phase I study (ARTIC M33/2).

Background: The antimalarial artesunate (ART), a semisynthetic derivative of artemisinin from the Chinese herb artemisia annua has remarkable anticancer properties in vitro and in vivo. Its excellent safety profile known from short-term therapy in malaria was confirmed in an open phase I trial (ARTIC M33/2) for dose-finding as add-on therapy for four weeks.

Purpose: Patients with metastatic breast cancer, who had not experienced any clinically relevant adverse events (AE) during participation in ARTIC M33/2, were offered to continue ART as compassionate use (CU).

Prospective open uncontrolled phase I study to define a well-tolerated dose of oral artesunate as add-on therapy in patients with metastatic breast cancer (ARTIC M33/2).

Purpose: The antimalarial drug artesunate (ART) is a promising candidate for cancer treatment as it displays anticancer effects in various models. While in short-term treatment of malaria, an excellent safety profile has been found for ART, the potential long-term treatment of cancer patients demands a phase I dose-finding clinical trial determining the daily ART dose which would be well tolerated as add-on therapy.

Methods: Patients with metastatic breast cancer were to receive either 100 or 150 or 200 mg oral ART daily as add-on to their guideline-based oncological therapy for a study period of four weeks with frequent clinical and laboratory monitoring until 4-8 weeks thereafter.

Interferon versus methotrexate in intermediate uveitis with macular edema: results of a randomized controlled clinical trial.

Purpose: To compare interferon (IFN) beta with methotrexate (MTX) in the treatment of intermediate uveitis with macular edema.

Design: Monocentric, prospective, randomized, controlled clinical trial.

Setting: Specialized uveitis center at the University of Heidelberg.

An unusual case of optic neuritis.

Optic neuritis is a frequent disease with well established tests and therapeutic strategies. However, possible differential diagnoses cover a broad spectrum. Therefore, clinical work-up can be challenging and routine testing and therapies may not be sufficient.

Rippling muscle disease: variable phenotype in a family with five afflicted members.

We report a family with rippling muscle disease (RMD) who had an autosomal dominant mode of inheritance. The father, mother, and one daughter proved to be heterozygous, and two sons were homozygous for the A92T mutation of the caveolin-3 gene. The cardinal features of RMD, particularly percussion-induced rapid contractions, muscle mounding, and muscle rippling, varied considerably among these subjects.

Aquaporin-4 antibody positive longitudinally extensive transverse myelitis following varicella zoster infection.

Longitudinally extensive transverse myelitis (LETM) is a condition shown to confer high risk of conversion into neuromyelitis optica (NMO). Increasing evidence from immunological and histopathological studies suggests that LETM is an autoimmune disorder caused by pathogenic antibodies to aquaporin-4 (AQP4-Ab), the most abundant water channel in the CNS, at least in a subset of patients. However, cases of infectious or parainfectious NMO/LETM (mostly associated with herpes zoster) have been repeatedly reported in the previous literature, raising the question of aetiological diversity in NMO/LETM.

Specific recruitment of regulatory T cells into the CSF in lymphomatous and carcinomatous meningitis.

Whereas regulatory T (Treg) cells play an important role in the prevention of autoimmunity, increasing evidence suggests that their down-regulatory properties negatively affect immune responses directed against tumors. Treg cells selectively express chemokine receptors CCR4 and CCR8, and specific migration occurs following the release of various chemokines. Neoplastic meningitis (NM) resulting from leptomeningeal spread of systemic non-Hodgkin lymphoma (NHL) or carcinoma has a poor prognosis.

Linezolid-induced posterior reversible leukoencephalopathy syndrome.

Objective: To describe a 71-year-old woman who developed clinical and neuroradiological features of posterior reversible leukoencephalopathy syndrome with a compromised blood-brain barrier after 5 days of intravenous linezolid therapy for an infected hip prosthesis.

Design: Case report.

Setting: Academic research.

Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis.

Immunoregulatory T cells of (CD4+)CD25+ phenotype suppress T cell function and protect rodents from organ-specific autoimmune disease. The human counterpart of this subset of T cells expresses high levels of CD25 and its role in human autoimmune disorders is currently under intense investigation. In multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), the activation of circulating self-reactive T cells with specificity for myelin components is considered to be an important disease initiating event.

Single-cell PCR analysis of the immunoglobulin heavy-chain CDR3 region for the diagnosis of leptomeningeal involvement of B-cell malignancies using standard cerebrospinal fluid cytospins.

The diagnosis of leptomeningeal B-cell malignancies is based on the identification of malignant B cells in the cerebrospinal fluid (CSF). We have established a polymerase chain reaction (PCR) approach to characterize the clonally diverse gene encoding the immunoglobulin heavy-chain (IgH) third complementarity determining region (CDR3) of single B cells. We demonstrate that single-cell PCR is readily applicable to individual cells derived from routine CSF cytospins and is a powerful method to discriminate monoclonal neoplastic from polyclonal reactive B-cell responses.

Thymic export function and T cell homeostasis in patients with relapsing remitting multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory and possibly autoimmune mediated demyelinating disease of the CNS. Autoimmunity within the CNS may be triggered by dysfunction of peripheral immune tolerance mechanisms via changes in the homeostatic composition of peripheral T cells. We have assessed the release of naive T lymphocytes from the thymus in patients with relapsing remitting MS (RRMS) to identify alterations in the equilibrium of the peripheral T cell compartment.

Intravascular lymphomatosis presenting with a conus medullaris syndrome mimicking disseminated encephalomyelitis.

We describe the clinical, radiologic, and postmortem findings of a 42-year-old man with intravascular lymphomatosis. The patient presented with a conus medullaris syndrome followed by progressive, disseminated spinal and cerebral symptoms. Disseminated encephalomyelitis was suspected due to the clinical, radiologic, and cerebrospinal fluid findings and the results of a stereotactic brain biopsy, all of which were compatible with inflammatory CNS disease.

Inducible nitric oxide synthase and argininosuccinate synthetase: co-induction in brain tissue of patients with Alzheimer's dementia and following stimulation with beta-amyloid 1-42 in vitro.

In Alzheimer's disease (AD), amyloid plaques within the brain are surrounded by activated glial cells (microglia and astrocytes). The mechanisms of glial activation and its effect on disease progression are not fully understood. Growing evidence suggests that beta-amyloid (Abeta) peptide, a major constituent of the amyloid plaque, is critically involved in the induction of an inflammatory response.