Mid- to long-term outcome of disc excision in adolescent disc herniation.

BACKGROUND CONTEXT: Adolescent disc herniation and its surgical treatment have been the subjects of many published clinical series. The majority of these series were heterogeneous; the number of adolescent patients (12-17 years) as opposed to young adults (18-20 years) was generally small and the length of follow-up varied greatly. Although the short-term outcome of disc excision in adolescents was mostly favorable, their long-term outcome is unknown. OBJECTIVES: To evaluate the mid- and long-term results of discectomy in patients younger than 17 years of age. STUDY DESIGN: Retrospective examination of a series of adolescent patients under the age of 17 years who underwent surgery for lumbar intervertebral disc herniation. PATIENT SAMPLE: The medical records of 26 patients (15 males, 11 females, 12-17 years old [average 14.6]) who were operated for lumbar intervertebral disc herniation in three spine centers between 1984 and 2002 were reviewed. These subjects represented the total number of patients meeting the criteria of adolescents undergoing discectomy for lumbar disc herniation in these institutions during the study period. All patients were located and contacted by an independent observer not involved in the care of these patients. Low back pain associated with leg pain was the main clinical symptom in 20 patients (77%), leg pain in 4 (15%), and back pain in 2 (8%). They all underwent posterior disc excision: 23 (88%) patients had one level discectomy, and 3 (12%) had simultaneous discectomy at two levels. The L4-L5 interspace was involved 19 times, and the L5-S1 interspace 10 times. Slipped vertebral apophysis was diagnosed in 4 patients (15%). Twelve of the 26 patients (46%) had a first-degree relative with a history of lumbar disc herniation. OUTCOME MEASURES: Telephone interviews provided follow-up data for 26 patients. Results were classified as excellent, good, moderate, or poor according to current symptom status, the need for additional surgery, the Oswestry Disability Index, and back and leg pain scores. RESULTS: The average time from surgery to follow-up was 8.9 years (range 3-21 years). At follow-up, the clinical results were excellent in 13 patients (50%), good in 4 (15%), moderate in 8 (31%), and poor in 1 (4%). Four subjects (15%) underwent a subsequent disc excision in the lumbar region, and one of them later underwent fusion. CONCLUSIONS: Discectomy provides satisfactory clinical results in young patients with disc herniation. The rate of reintervention (15%) is comparable to that in adults, indicating that discectomy for young patients should be approached similarly to that in adults.     

Analysis of gene expression in MOG-induced experimental autoimmune encephalomyelitis after treatment with a novel brain-penetrating antioxidant

Accumulating data from experimental studies indicate that oxidative stress has a major role in the pathogenesis of multiple sclerosis (MS). It has been suggested that local production of reactive oxygen species, probably by macrophages, mediates axonal damage in both MS patients and the mouse model experimental autoimmune encephalomyelitis (EAE). We have shown previously that our novel brain-penetrating antioxidant, N-acetylcysteine amide (AD4), reduces the clinical and pathological symptoms, including inflammation and axonal damage in myelin oligodendrocyte glycoprotein (MOG)-induced chronic EAE in mice. The aim of this study was to examine the molecular mechanism by which AD4 exerts protection in MOG-induced EAE mice. Therefore, we analyzed gene-expression profile in the spinal cords of MOG-induced chronic EAE mice and compared them with MOG-induced mice treated with AD4, using a cDNA microarray. We found that MOG treatment up-regulated genes encoding growth factors, cytokines, death receptors, proteases, and myelin structure proteins, whereas MOG- and AD4-treated mice demonstrated gene expression profiles similar to that seen in na?ve healthy mice. In conclusion, our study shows that chronic AD4 administration suppresses the induction of various pathological pathways that play a role in EAE and probably in MS.     

The early recognition of dementia in the elderly: A preliminary communication about a longitudinal study using the gms–agecat package (community version)

A random community sample of 1070 subjects aged over 65 was interviewed by trained non-medical interviewers using the Geriatric Mental State, community version (GMSA). A sub-sample of 126 subjects was selected so as to contain possible early cases of dementia, pseudo-dementia, and normal subjects; and re-interviewed, a mean 1 year and 23 weeks later, by a group of psychiatrists in training. The computer diagnosis AGECAT, based on GMSA applied by non-medical raters, had predicted at initial interview, nine out of twelve cases of dementia at follow-up and five out of nine borderline cases. An Organic/Depression Index may prove useful in predicting which of those cases with early organic levels will eventually develop dementia, depression or recover.     

Stress signaling through Ca2+/calmodulin-dependent protein phosphatase calcineurin mediates salt adaptation in plants

Calcineurin (CaN) is a Ca²⁺- and calmodulin-dependent protein phosphatase (PP2B) that, in yeast, is an integral intermediate of a salt-stress signal transduction pathway that effects NaCl tolerance through the regulation of Na⁺ influx and efflux. A truncated form of the catalytic subunit and the regulatory subunit of yeast CaN were coexpressed in transgenic tobacco plants to reconstitute a constitutively activated phosphatase in vivo. Several different transgenic lines that expressed activated CaN also exhibited substantial NaCl tolerance, and this trait was linked to the genetic inheritance of the CaN transgenes. Enhanced capacity of plants expressing CaN to survive NaCl shock was similar when evaluation was conducted on seedlings in tissue culture raft vessels or plants in hydroponic culture that were transpiring actively. Root growth was less perturbed than shoot growth by NaCl in plants expressing CaN. Also, NaCl stress survival of control shoots was enhanced substantially when grafted onto roots of plants expressing CaN, further implicating a significant function of the phosphatase in the preservation of root integrity during salt shock. Together, these results indicate that in plants, like in yeast, a Ca²⁺- and calmodulin-dependent CaN signal pathway regulates determinants of salt tolerance required for stress adaptation. Furthermore, modulation of this pathway by expression of an activated regulatory intermediate substantially enhanced salt tolerance.     

Duchenne muscular dystrophy and idiopathic hyperCKemia segregating in a family

A 7-month-old boy with gross motor delay and failure to thrive presented with rhabdomyolysis following an acute asthmatic episode. During hospitalization an electrocardiographic conversion to a Wolff-Parkinson-White type 1 (WPW) pattern took place. Duchenne muscular dystrophy (DMD) was suspected based on elevated creatine kinase (CK) serum levels, muscle biopsy, and family history. The diagnosis was confirmed by molecular analysis, which documented a deletion corresponding to cDNA probe 1-2a in the dystrophin gene, in the propositus and in an affected male cousin of his mother. “Idiopathic” hyperCKemia was found in the propositus, his father, and 5 of his relatives. We suggest that the unusually early and severe manifestations of DMD in this patient may be related to the coincidental inheritance of the maternal DMD gene and of a paternal gene, causing hyperCKemia. © 1995 Wiley-Liss, Inc.     

From the Cover: Echolocating bats rely on an innate speed-of-sound reference

Animals must encode fundamental physical relationships in their brains. A heron plunging its head underwater to skewer a fish must correct for light refraction, an archerfish shooting down an insect must “consider” gravity, and an echolocating bat that is attacking prey must account for the speed of sound in order to assess its distance. Do animals learn these relations or are they encoded innately and can they adjust them as adults are all open questions. We addressed this question by shifting the speed of sound and assessing the sensory behavior of a bat species that naturally experiences different speeds of sound. We found that both newborn pups and adults are unable to adjust to this shift, suggesting that the speed of sound is innately encoded in the bat brain. Moreover, our results suggest that bats encode the world in terms of time and do not translate time into distance. Our results shed light on the evolution of innate and flexible sensory perception.

Every organism must reliably sense its environment in order to survive and reproduce (1). Some sensory systems are innate and unalterable (2), allowing for efficient use even by naïve newborn animals (3–5). Others require learning or experience-dependent development—usually during a critical period during ontogeny (6, 7), though sometimes retained through adulthood (8), allowing for adapting sensing to changing environments (9, 10). The ability to accurately estimate distances with sub-centimeter accuracy is a hallmark of bat echolocation (11–13). Bats achieve this accuracy by means of delay-tuned neurons—neurons that are activated by specific call–echo time delays, supposedly encoding target distance (14–19), although it should be noted that some work suggests that the tuning width of delay-tuned neurons might not allow the accuracy that bats exhibit in delay perception (20). Though delay tuning has been shown to be (at least partially) innate at the neural level (21), this has never been tested behaviorally. Namely, when a newborn bat takes off for the first time, does its brain correctly translate time delays into distance?Translating time into distance relies on a reference of the speed of sound (SOS). This physical characteristic of the environment is not as stable as it may seem. The SOS may change considerably due to various environmental factors such as humidity, altitude, and temperature (22). Bats (Chiroptera) are a specious and widely distributed order of highly mobile and long-lived animals. They therefore experience a range of SOSs (with more than 5% variation, see below) between species, among species, and even within the life of a single individual. We therefore speculated that the reference of the SOS may not be innate to allow for the environmentally dependent SOS experienced by each animal.To test this, we examined the acquisition of the SOS reference by exposing neonatal bats to an increased SOS environment from birth (Materials and Methods). We reared two groups of bats from birth to independent flight in two flight chambers: six bats in normal air (henceforth: “air pups”) and five bats in a helium-enriched air environment (Heliox), where the speed of sound was 15% higher (henceforth: “Heliox pups”). Notably, Heliox pups were never active and did not echolocate in non-Heliox environment (Materials and Methods). This 15% shift is higher than the ecological range and was chosen because it is high enough to enable us to document behavioral changes but low enough so as to allow the bats to function (that is, to fly despite the change in air density). In order to feed, the bats had to fly to a target positioned 1.3 m away from their wooden slit roost. Once the bats learned to fly to the target independently (after ca. 9 wk), we first documented their echolocation in the environment where they were brought up, and we then moved them to the other treatment for testing (Materials and Methods). Because bats adjust their echolocation parameters to the distance of the target, before and during flight (23), we used their echolocation to assess the bats’ target range estimates. If the SOS reference is learned based on experience, the bats raised in Heliox should have learned a faster reference, so that when they flew in normal air, they would have perceived the target as farther than it really was. We also ran the same experiments on adult bats to test adult plasticity.     

Umbilical cord blood transplantation--how, when and for whom?

In recent years, umbilical cord blood (UCB) has emerged as a feasible alternative source of hematopoietic progenitors (CD34+) for allogeneic stem cell transplantation, mainly in patients who lack HLA-matched marrow donors. Since the first case reported in 1998, more than 3500 patients have received UCB transplants for a variety of malignant and non-malignant diseases. The vast majority of recipients were children with an average weight of 20 kg; however, more than 500 UCB transplantations (UCBTs) have already been performed in adults. The "naive" nature of UCB lymphocytes also permits the use of HLA-mismatched grafts at 1-2 loci without higher risk for severe graft versus host disease (GvHD) relative to bone marrow transplantation (BMT) from a full matched unrelated donor. Furthermore, UCB is rich in primitive CD16(-)CD56++ NK cells, which possess impressive proliferative and cytotoxic capacities and can be induced to expand using IL-12 or IL-15, so as to mount a substantial graft versus leukemia (GvL) effect. The main disadvantage of UCB is the low stem cell yields, resulting in higher rates of graft failure as well as delayed time to engraftment compared to BMT. One rational approach to overcome this limitation involves ex vivo expansion of UCB derived hematopoietic precursors. In this review we tried to answer the question: UCBT how, when and for whom. This procedure is mostly applicable for children and especially those with indication for full allogeneic transplantation but who lack a matched sibling donor. Experimental approaches including ex vivo expansion of CB with cocktail of hematopoietic growth factors, with or without differentiation blocking agents, co-transplantation of haploidentical and CB cells or co-transfusion of CB and mesenchymal cells may enable successful UCBT in adults and probably will result in expanding the indication to solid tumors or autoimmune disorders.