Multiple sclerosis: Identification and clinical evaluation of novel CSF biomarkers.

Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that results in damage to myelin sheaths and axons in the central nervous system and which preferentially affects young adults. We performed a proteomics-based biomarker discovery study in which cerebrospinal fluid (CSF) from MS and control individuals was analyzed (n=112). Ten candidate biomarkers were selected for evaluation by quantitative immunoassay using an independent cohort of MS and control subjects (n=209). In relapsing-remitting MS (RRMS) patients there were significant increases in the CSF levels of alpha-1 antichymotrypsin (A1AC), alpha-1 macroglobulin (A2MG) and fibulin 1 as compared to control subjects. In secondary progressive MS (SPMS) four additional proteins (contactin 1, fetuin A, vitamin D binding protein and angiotensinogen (ANGT)) were increased as compared to control subjects. In particular, ANGT was increased 3-fold in SPMS, indicating a potential as biomarker of disease progression in MS. In PPMS, A1AC and A2MG exhibit significantly higher CSF levels than controls, with a trend of increase for ANGT. Classification models based on the biomarker panel could identify 70% of the RRMS and 80% of the SPMS patients correctly. Further evaluation was conducted in a pilot study of CSF from RRMS patients (n=36), before and after treatment with natalizumab.

Identification of novel candidate protein biomarkers for the post-polio syndrome - implications for diagnosis, neurodegeneration and neuroinflammation.

Survivors of poliomyelitis often develop increased or new symptoms decades after the acute infection, a condition known as post-polio syndrome (PPS). The condition affects 20-60% of previous polio patients, making it one of the most common causes of neurological deficits worldwide. The underlying pathogenesis is not fully understood and accurate diagnosis is not feasible. Herein we investigated whether it was possible to identify proteomic profile aberrations in the cerebrospinal fluid (CSF) of PPS patients. CSF from 15 patients with well-defined PPS were analyzed for protein expression profiles. The results were compared to data obtained from nine healthy controls and 34 patients with other non-inflammatory diseases which served as negative controls. In addition, 17 samples from persons with secondary progressive multiple sclerosis (SPMS) were added as relevant age-matched references for the PPS samples. The CSF of persons with PPS displayed a disease-specific and highly predictive (p=0.0017) differential expression of five distinct proteins: gelsolin, hemopexin, peptidylglycine alpha-amidating monooxygenase, glutathione synthetase and kallikrein 6, respectively, in comparison with the control groups. An independent ELISA confirmed the increase of kallikrein 6. We suggest that these five proteins should be further evaluated as candidate biomarkers for the diagnosis and development of new therapies for PPS patients.

The vulnerability of orphans in Thyolo District, southern Malawi.

It is estimated that Malawi has about 900,000 orphans, the majority of whom are orphaned as a result of AIDS. Orphans in rural areas are mostly neglected by economic and social empowerment initiatives. This study was conducted to explore the living situation of orphans in rural Thyolo District, southern Malawi. Qualitative methodology was used in data collection and analysis to explore orphan children's living situation and specifically with regard to access to health care, education, food and basic needs. In addition, issues of love and companionship, discrimination and the future. Twenty-three orphan children and four adults were interviewed. The children reported experience with lack of food, school drop out and truancy, lack of social support to obtain present needs and prepare for the future. Public health programs aimed to prevent and mitigate the effects of AIDS in Malawi should be tailored to provide support to orphan children.

[Old gender patterns still used when physicians are pictured in medical journals. Male physicians are portrayed as active leaders, women physicians as listening, compassionate]. / Bilder av läkare i fackpress visar gamla genusmtönster i ny stöpning. Män framställs som aktiva, ledande--kvinnor som lyssnande, inkännande.

As a part of a medical student' s research project on medical socialisation, the 2002 issue of two Swedish medicaljournals, Läkartidningen and Moderna Läkare, were scrutinized regarding how male and female physicians were represented on pictures. The outward façade was mostly male; 87% of portrays of editorials pictured a man, 81% of career announcements displayed men. Authors of articles and chroniclers more often presented a female face (55%). Photos in reports showed around 60% men and 40 % women, both regarding area and number of photos. These shares corresponded well to the actual share of male and female physicians in Sweden. The content analysis of pictures, however, demonstrated gender features: men were to a much higher degree focused in leading, demonstrating and speaker positions, while women to a higher degree were portrayed as taking part in consultations or caring activities.

Extraction and proteomic analysis of proteins from normal and multiple sclerosis postmortem brain.

In this study, a reproducible fractionation procedure was developed to reduce levels of the abundant cytoskeletal proteins that are present in normal and pathological central nervous system (CNS) tissues. The fractionation and proteomic analysis techniques employed greatly facilitated comparison of the spectrum of proteins in normal postmortem brain with proteins in samples from patients with multiple sclerosis, an inflammatory demyelinating disease in which complex changes in protein expression occur as lesions develop. This approach may be of value for the proteomic identification and quantitation of proteins which undergo disease-related changes in CNS disorders, and also for protein expression studies on normal adult and developing CNS tissues.