Multiple sclerosis with clinical and radiological features of cerebral tumour

Three cases of multiple sclerosis, all confirmed pathologically, are described in whom both the unusual clinical features and the CT scan appearances suggested cerebral tumours. The failure of mass effect reliably to differentiate plaques and tumours on a CT scan is stressed and the literature relating to CT scanning in multiple sclerosis is reviewed.     

Preferences for rehabilitation services among women with major limb amputations

Purpose

We present five cases of adult females with major limb amputations, their concerns and preferences for services across the life span.

Design

A convenience sample of five veteran and nonveteran women aged 19–58 with major limb amputations participating in a regional VA Prosthetics Conference in 2010 took part in a panel interview.

Findings

The concerns identified by these women as high priorities included independence and participation in a full range of life activities, limitations in access, patient decision‐making and body image concerns, and preferences for selected services. Maximizing function and quality of life for women amputees requires identifying patient preferences for rehabilitation and prosthetic services. Lessons learned could inform development of clinic‐based rehabilitation care, prosthetic services, and studies of women with major limb amputations.

Conclusions

As the current conflicts in Iraq and Afghanistan wind down, the number of women veterans seeking rehabilitation and prosthetic services will increase. With this information, rehabilitation and prosthetic service providers and organizations will be uniquely positioned to provide prevention and treatment of amputations for this growing population of women veterans in national care delivery systems and in communities.

Clinical Relevance

An open‐ended facilitated discussion among a panel of women with major limb amputations provided insights for providers and organizations with respect to needs, concerns, and preferences for rehabilitation and prosthetic services.     

Pharmacodynamic analysis of a serine protease inhibitor, MK-4519, against hepatitis C virus using a novel in vitro pharmacodynamic system

The development of new antiviral compounds active against hepatitis C virus (HCV) has surged in recent years. In order for these new compounds to be efficacious in humans, optimal dosage regimens for each compound must be elucidated. We have developed a novel in vitro pharmacokinetic/pharmacodynamic system, the BelloCell system, to identify optimal dosage regimens for anti-HCV compounds. In these experiments, genotype 1b HCV replicon-bearing cells (2209-23 cells) were inoculated onto carrier flakes in BelloCell bottles and treated with MK-4519, a serine protease inhibitor. Our dose-ranging studies illustrated that MK-4519 inhibited replicon replication in a dose-dependent manner, yielding a 50% effective concentration (EC(50)) of 1.8 nM. Dose-fractionation studies showed that shorter dosing intervals resulted in greater replicon suppression, indicating that the time that the concentration is greater than the EC(50) is the pharmacodynamic parameter for MK-4519 linked with inhibition of replicon replication. Mutations associated with resistance to serine protease inhibitors were detected in replicons harvested from all treatment arms. These data suggest that MK-4519 is highly active against genotype 1b HCV, but monotherapy is not sufficient to prevent the amplification of resistant replicons. In summary, our findings show that the BelloCell system is a useful and clinically relevant tool for predicting optimal dosage regimens for anti-HCV compounds.     

Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis

Apoptosis, or programmed cell death, is a general mechanism for removal of unwanted cells from the immune system. It is characterized by chromatin condensation, a reduction in cell volume, and endonuclease cleavage of DNA into oligonucleosomal length fragments. Apoptosis is also accompanied by a loss of membrane phospholipid asymmetry, resulting in the exposure of phosphatidylserine at the surface of the cell. Expression of phosphatidylserine at the cell surface plays an important role in the recognition and removal of apoptotic cells by macrophages. Here we describe a new method for the detection of apoptotic cells by flow cytometry, using the binding of fluorescein isothiocyanate-labeled annexin V to phosphatidylserine. When Burkitt lymphoma cell lines and freshly isolated germinal center B cells are cultured under apoptosis inducing conditions, all cells showing chromatin condensation strongly stain with annexin V, whereas normal cells are annexin V negative. Moreover, DNA fragmentation is only found in the annexin V-positive cells. The nonvital dye ethidium bromide was found to stain a subpopulation of the annexin V-positive apoptotic cells, increasing with time. Our results indicate that the phase in apoptosis that is characterized by chromatin condensation coincides with phosphatidylserine exposure. Importantly, it precedes membrane damage that might lead to release from the cells of enzymes that are harmful to the surrounding tissues. Annexin V may prove important in further unravelling the regulation of apoptosis.