Alignment of new tuberculosis drug regimens and drug susceptibility testing: a framework for action.

New tuberculosis drug regimens are creating new priorities for drug susceptibility testing (DST) and surveillance. To minimise turnaround time, rapid DST will need to be prioritised, but developers of these assays will need better data about the molecular mechanisms of resistance. Efforts are underway to link mutations with drug resistance and to develop strain collections to enable assessment of new diagnostic assays.

New drugs for the treatment of tuberculosis: needs, challenges, promise, and prospects for the future.

For the first time in 40 years, a portfolio of promising new compounds for the treatment of tuberculosis is on the horizon. The introduction of new drugs in combination treatment for all forms of tuberculosis raises several issues related to patients' access to novel treatments, programmatic feasibility, cost effectiveness, and implications for monitoring and surveillance, particularly with regard to the development of drug resistance. Particular attention should be given to the identification of optimal drug combination(s) for the treatment of all forms of tuberculosis, particularly in high-risk and vulnerable groups, such as human immunodeficiency virus-coinfected persons and children, and to the rational use of new drugs.

Safety and pharmacokinetics of the neuroprotective drug lubeluzole in patients with ischemic stroke.

A total of 22 patients with acute ischemic stroke participated in two randomized, single-masked, placebo-controlled studies that evaluated the safety and pharmacokinetics of single escalating intravenous doses of lubeluzole. The first dose of study medication in all patients was given within 6 hours of the first sign of stroke onset. In the first study, 6 patients received a single 1-hour intravenous infusion of 5 mg of lubeluzole; 4 of these patients received an additional 10-mg dose 3 to 4 days later.

The safety and tolerability of single intravenous doses of lubeluzole (Prosynap) in healthy volunteers.

The safety and tolerability of single escalating doses of lubeluzole were evaluated in healthy male volunteers in 2 studies. In the first of 2 randomized, single-blind, placebo-controlled, dose-escalation studies, 6 subjects received single 30-minute infusions of 2.5, 5, and 10 mg of lubeluzole, and 2 additional subjects received placebo.

Hospital referral of stroke patients: a survey of attitudes in general practice, and consideration of entry times for clinical trials.

Two major issues in clinical trials in stroke are the criteria used for the selection of patients expected to benefit from the proposed treatment, and the entry time of those patients. We surveyed 507 Belgian general practitioners (GPs) on their opinions on referral of stroke patients to hospital and also on their actual referral behaviour. The feasibility of a 6-hour entry time was included in the investigation.

Reciprocal translocation between the proximal regions of the long arms of chromosomes 13 and 15 resulting in unbalanced offspring: characterization by fluorescence in situ hybridization and DNA analysis.

We describe two female siblings with similar clinical features consisting of hydrocephalus, scaphocephaly, hypotonia, mongoloid eye slant, blepharophimosis, micrognathia, supernumerary mouth frenula and mental retardation. Routine cytogenetic studies in the elder patient did not reveal any abnormality, and initially it was assumed that the syndrome had an autosomal recessive inheritance. However, a slightly larger chromosome 13 was seen in routine G-banded metaphases of the mother and the youngest of the two siblings.

Immunocytochemical detection of the growth-associated protein B-50 by newly characterized monoclonal antibodies in human brain and muscle.

The growth-associated protein B-50 also termed GAP-43, F1, pp46, P-57 and neuromodulin is a nervous tissue-specific protein kinase C (PKC) substrate that is considered to play a major role in neurite formation, regeneration, and neuroplasticity. We describe the isolation of seven mouse monoclonal antibodies (Mabs) directed against B-50. The Mabs are produced against the bovine B-50, selected by ELISA for cross-reactivity with its human counterpart, and evaluated on Western blots in comparison with the well-characterized affinity-purified rabbit polyclonal antibodies to rat-B-50.

Affinity purification of human tau proteins and the construction of a sensitive sandwich enzyme-linked immunosorbent assay for human tau detection.

Immunoaffinity chromatography with a monoclonal antibody produced against bovine tau protein was used to purify tau proteins from human brain. Fifty grams of brain tissue yielded approximately 2 mg of pure tau proteins. The affinity-purified human tau was used to produce a high-titered rabbit anti-human tau serum.

Monoclonal antibodies with selective specificity for Alzheimer Tau are directed against phosphatase-sensitive epitopes.

A modified form of the microtubule-associated protein Tau is the major component of the paired helical filaments (PHF) found in Alzheimer's disease. The characterization of these posttranslational Tau modifications is hindered by the lack of sufficient PHF-Tau-specific markers. Here we describe several monoclonal antibodies, prepared by immunization with PHF, two of which showed a selective specificity for PHF-Tau without cross-reactivity with normal Tau.

Specific monoclonal antibodies against normal microtubule-associated protein-2 (MAP2) epitopes present in Alzheimer pathological structures do not recognize paired helical filaments.

We have developed monoclonal antibodies that detect normal microtubule-associated protein-2 (MAP2) epitopes in routinely fixed, paraffin-embedded tissue. The somatodendritic distribution of MAP2 in bovine and human nervous tissue was confirmed with several of these antibodies. Furthermore, some of these antibodies immunohistochemically labeled certain pathological structures in Alzheimer brain, especially neurites in senile plaques.

Long term follow-up of multiple sclerosis by standardized, non-contrast-enhanced magnetic resonance imaging.

The usefulness of non-contrast-enhanced, standardized magnetic resonance imaging for the longterm follow-up of MS patients was evaluated in a retrospective study in 36 patients with clinically definite MS. All had remitting-relapsing diseases courses. Sixteen patients remained clinically stable during follow-up.

Demonstration of a novel neurofilament associated antigen with the neurofibrillary pathology of Alzheimer and related diseases.

A monoclonal antibody, termed NFT200, was raised after in vitro immunization with sonicated neurofibrillary tangle (NFT)-enriched fractions prepared from Alzheimer brain. The antigen to which NFT200 is directed was expressed in the paired helical filaments of NFT in sporadic and familial Alzheimer disease (AD), in the straight filaments of NFT in AD, progressive supranuclear palsy and of Pick bodies, and the NFT in several other conditions such as Parkinson-dementia complex of Guam and subacute sclerosing panencephalitis. Granulovacuolar degeneration of AD was also labeled with NFT200.

Isolation of IgG1-secreting switch variants from IgM hybridomas produced after in vitro immunization.

IgG1-secreting variants have been isolated from three different IgM-secreting hybridomas, in two instances following in vitro immunization. The method used was based on sequential sublining in combination with selection by an IgG1-specific two-site ELISA system employing two different IgG1-specific polyclonal antisera. Idiotypic identity between the IgG1 variants and their respective IgM parent was demonstrated using syngeneic anti-idiotypic antisera.

Early-onset Alzheimer's disease in 2 large Belgian families.

Familial Alzheimer's disease (FAD) is a dominantly inherited condition that may present with an early onset, and myoclonus occurs frequently in the course of the disease. We report clinical and neuropathologic data on 2 large Belgian families with FAD in which we obtained 17 autopsies of the CNS. In family A, each of 11 autopsies had the typical neuropathologic features of Alzheimer's disease (AD), and there were a few cerebellar plaques in the molecular layer.

Assignment of the Charcot-Marie-Tooth neuropathy type 1 (CMT 1a) gene to 17p11.2-p12.

Charcot-Marie-Tooth disease type 1a (CMT 1a) is an autosomal dominant peripheral neuropathy linked to the DNA markers D17S58 and D17S71, located in the pericentromeric region of the chromosome 17p arm. We analyzed an extended 5-generation Belgian family, multiply affected with CMT 1a, for linkage with eight chromosome 17 markers. The results indicated that the CMT 1a mutation is localized in the chromosomal region 17p11.

A monoclonal antibody raised against Alzheimer cortex that specifically recognizes a subpopulation of microglial cells.

A monoclonal antibody (MAb), termed AMC30, was raised after in vitro immunization with sonicated neurofibrillary tangle (NFT)-enriched fractions prepared from Alzheimer's brain. The antigen to which AMC30 is directed was expressed by microglial cells in senile plaques of Alzheimer's disease (AD). Microglia in the parenchyma surrounding brain tumors or infarctions, multinuclear giant cells, perivascular and parenchymal macrophages throughout the brain of AIDS patients were also labeled.

Improved correlation of magnetic resonance imaging (MRI) with clinical status in multiple sclerosis (MS) by use of an extensive standardized imaging-protocol.

In a previous study we have shown that the sensitivity of magnetic resonance imaging (MRI) for the detection of multiple sclerosis (MS) lesions was improved significantly, especially in the infratentorial region, by use of an extensive standardized MRI-protocol consisting of sagittal T1, axial protondensity and axial T2, and sagittal protondensity and sagittal moderately T2-weighted images. The goal of the present study was to assess whether the clinical correlation of the visualized lesions had improved accordingly. Using a scoring system based on lesion dimensions, we compared 70 MRI examinations performed in 25 patients with definite MS, with the relevant clinical data as given by the Expanded Disability Status Scale (EDSS) and Functional System scale (FS).

Localization of the mutation in an extended family with Charcot-Marie-Tooth neuropathy (HMSN I).

Hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth (CMT) disease is an autosomal dominant peripheral neuropathy. In some CMT families linkage has been reported with either the Duffy blood group or the APOA2 gene, both located on chromosome 1q. More recently, linkage has been found in six CMT families with two chromosome 17p markers.

Lazarus sign and extensor posturing in a brain-dead patient. Case report.

A man was declared brain dead after having sustained a gunshot wound to the head. All clinical criteria for the diagnosis of brain death were met. The electroencephalogram was isoelectric, and four-vessel angiography demonstrated the absence of cerebral blood flow.

Absence of genetic linkage of Charcot-Marie-Tooth disease (HMSN Ia) with chromosome 1 gene markers.

We previously reported a large Charcot-Marie-Tooth family not linked to the Duffy blood group marker, supporting the existence of genetic heterogeneity in this neuropathy. In order to investigate the possibility of another disease locus on chromosome 1, we analyzed this family further, using DNA polymorphisms of 6 genes. Absence of linkage makes a second disease locus on chromosome 1 unlikely.