Irwin M. Siegel

Human neural stem cell transplants improve motor function in a rat model of Huntington's disease

The present study investigated the neuroanatomical and behavioral effects of human stem cell transplants into the striatum of quinolinic acid (QA)‐lesioned rats. Twenty‐four rats received unilateral QA (200 nM/μl) injections into the striatum. One week later, rats were transplanted with stem cells derived from human fetal cortex (12 weeks postconception) that were either 1) pretreated in culture media with the differentiating cytokine ciliary neurotrophic factor (CNTF; n = 9) or 2) allowed to grow in culture media alone (n = 7). Each rat was injected with a total of 200,000 cells. A third group of rats (n = 8) was given a sham injection of vehicle. Rats transplanted with human stem cells performed significantly better over the 8 weeks of testing on the cylinder test compared with those treated with vehicle (P ≤ 0.001). Stereological striatal volume analyses performed on Nissl‐stained sections revealed that rats transplanted with CNTF‐treated neurospheres had a 22% greater striatal volume on the lesioned side compared with those receiving transplants of untreated neurospheres (P = 0.0003) and a 26% greater striatal volume compared with rats injected with vehicle (P ≤ 0.0001). Numerous human nuclei‐positive cells were visualized in the striatum in both transplantation groups. Grafted cells were also observed in the globus pallidus, entopeduncular nucleus, and substantia nigra pars reticulata, areas of the basal ganglia receiving striatal projections. Some of the human nuclei‐positive cells coexpressed glial fibrillary acidic protein and NeuN, suggesting that they had differentiated into neurons and astrocytes. Taken together, these data demonstrate that striatal transplants of human fetal stem cells elicit behavioral and anatomical recovery in a rodent model of Huntingtons disease. J. Comp. Neurol. 475:211–219, 2004.

'On' freezing in Parkinson's disease: Resistance to visual cue walking devices

To measure “on” freezing during unassisted walking (UW) and test if two devices, a modified inverted stick (MIS) and a visual laser beam stick (LBS) improved walking speed and number of “on” freezing episodes in patients with Parkinsons disease (PD).

Maintenance of Ambulation in Duchenne Muscular Dystrophy: The Role of the Orthopedic Surgeon

As the processes of pseudohypertrophic muscular dystrophy advance, contractures about joints in the lower extremities progress until an unstable base of support secondary to equinovarus and weakened pelvic balance produced by hip flexion prohibit ambulation. Properly timed surgery and bracing have helped some patients to extend significantly their ability to ambulate. Because severe weakness can result from prolonged restraint, opera tive procedures must permit immediate mobilization without fear of excessive pain or wound dehiscence. The primary aims of surgery are to maintain standing balance and prolong independent ambulation. Conditions requiring surgical correction are lower extremity flexion contracture, metatarsus adductus, and rigid forefoot equinocavovarus. Techniques designed to improve these deformities and permit early postoperative mobilization include subcutaneous release of contracted tendons and percutaneous removal of cancellous bone with corrective manipulation of the feet. Postoperative plastic bracing enhances balance through mild knee flexion and ischial seating. Maintenance of the upright posture extends the ability of these patients to attend to their tasks of daily living. In addition, these techniques offer a method of prolonging ambulation in the patient with pseudohypertrophic muscular dystrophy. In so doing, confinement to a wheelchair with its inevitable downhill course may be significantly postponed.

Charcot and Duchenne: Of Mentors, Pupils, and Colleagues

In the history of medicine, there have been notable mentors, famous pupils, and celebrated colleagues. Seldom, however, have two renowned physicians simultaneously been mentors, pupils, and colleagues to each other, as was the case with Jean-Martin Charcot (Fig. 1) and Guillaume Benjamin Amand Duchenne (Fig. 2). Notwithstanding a 19-year difference in age and the fact that each was a well-published neurological scientist in his own right, these investigators developed a multifaceted relationship which served to reciprocally foster their separate vocations, enhance their mutual endeavors, and enrich the field of neurology. This study examines the teaching, learning, and scientific sharing that uniquely marked the careers of Charcot and Duchenne.

Mommy, Kiss It and Make It Well saliva reconsidered—some reflections on alloantisepsis

Human saliva is a two-edged sword. The mouth can infect, and it can also heal. Saliva is a component of the immune system. Many antibacterial factors as well as digestive enzymes are present in sputum, and oxidizing agents abet oral defense mechanisms. The biological equilibrium of the mouth enhances its antimicrobial environment. Saliva cleans the wound by lavage, promoting healing while protecting injured tissues. Awareness of both the adverse and salubrious effects of sputum should inform the treatment of wounds with oral contact.