Transport in a grooved perfusion flat-bed bioreactor for cell therapy applications

We retrospectively reviewed the cases of seventy-two consecutive patients who had a lumbar discectomy, between 1950 and 1983, when they were sixteen years of age or younger. There were forty boys and thirty-two girls. At the time of the lumbar discectomy, twelve patients (17 per cent) also had a spinal arthrodesis. The mean duration of follow-up was 27.8 years (range, twelve to forty-five years). Twenty patients (28 per cent) had one reoperation or more, with the first reoperation performed at a mean of 9.7 years after the initial discectomy. Fourteen patients had one reoperation, four had two reoperations, one had three, and one had five. Fifty-two patients (72 per cent) did not need a reoperation. At the time of the latest follow-up, forty-eight (92 per cent) of the fifty-two patients either had no pain or had occasional pain related to strenuous activity and fifty-one (98 per cent) could participate in daily activities with no or mild limitations. Survivorship analysis showed that the overall probability that a patient would not need a reoperation was 80 per cent at ten years and 74 per cent at twenty years after the initial operation. With the numbers available for study, we could not show that age, gender, or an arthrodesis performed at the time of the initial operation were risk factors for a reoperation. We could not detect a difference, with respect to pain or the level of activity, between the patients who had had an arthrodesis at the initial operation and those who had not or between those who had a coexisting structural abnormality of the lumbar spine and those who did not.     

Waiting lists for psychogeriatric nursing home admissions: insight into the problematic waiting times

The distribution, morphological features, and postnatal development of parvalbumin (PV) immunoreactive neurons in the main olfactory bulb (MOB) of the house musk shrew, Suncus murinus, were studied to report for the first time on PV positive bulbar interneurons in the order Insectivora. In adult animals, PV neurons are distributed in the glomerular layer (GL), the external plexiform layer (EPL), the internal plexiform layer (IPL) and the granule cell layer (GCL) of the MOB. These neurons were identified as a subpopulation of periglomerular cells and perinidal cells [Alonso et al., 1995] in the GL and at the GL-EPL border, respectively, and as bipolar and multipolar neurons in the EPL and four types of the interneurons (horizontal cells, Cajal cells, Golgi cells, and bitufted cells) in the layers deeper than the mitral cell layer. During development of PV neurons, neurons exhibiting extremely faint PV immunoreactivity first appeared in the GCL at postnatal day 14 and increased markedly in number and intensity of their PV immunoreactivity from postnatal days 14 to 28. At postnatal day 21, PV neurons were identified as periglomerular cells in the GL, perinidal cells at the GL-EPL border, and morphologically unidentifiable neurons in the EPL, IPL and GCL. At postnatal day 28, PV neurons exhibited a nearly adult pattern with respect to distribution and structural features. The present results strongly suggest that a wide variety of PV positive neurons in the MOB of the house musk shrew may develop postnatally.     

Closely spaced recurrent hippocampal seizures elicit two types of heightened epileptogenesis: a rapidly developing, transient kindling and a slowly developing, enduring kindling

Kindling is widely accepted as a model of chronic epilepsy as well as a model of plasticity in the nervous system. Conventional kindling studies have used infrequent stimuli (separated by many hours) to establish a fully kindled state in which enhanced responses (kindled motor seizures and protracted afterdischarges) are consistently triggered by stimuli that initially did not elicit such responses. The enhanced responses occur even after a prolonged stimulus-free interval. Whereas the establishment of a kindled state with traditional stimulus protocols takes several weeks, our previous work showed that kindling could take place much more quickly when the interstimulus interval was set at 30 min (rapid kindling). In this report we tested whether rapid kindling protocols share with traditional kindling protocols the ability to establish a fully kindled state. Using different stimulus protocols involving recurrent hippocampal seizures, we characterized two types of kindling. 'Rapid kindling' developed over hours, but was transient, with a decay rate of a few days so that a fully kindled state did not persist. In contrast, 'slow kindling' developed over several weeks and was enduring, apparently permanent, being associated with a fully kindled state. These findings suggest that, while having certain similarities, the two types of kindling arise from dissimilar mechanisms. The existence of these two types of kindling has implications for epileptogenesis in humans. Moreover, the protocols developed in this work provide a useful means to control for the effects of seizures that are not related to mechanisms underlying a fully kindled state.     

Effect of vitamin E on the anticoagulant response to warfarin

To clarify whether vitamin E enhances the pharmacologic effect of warfarin, we completed a double-blind clinical trial in which 21 subjects taking chronic warfarin therapy were randomized to receive either vitamin E or placebo. None of the subjects who received vitamin E had a significant change in the international normalized ratio, and thus it appears that vitamin E can safely be given to patients who require chronic warfarin therapy.     

Naloxone''s effects on operant responding depend upon level of deprivation

Treadmill exercise activates the hypothalamic-pituitary-adrenal axis and evokes metabolic responses proportional to exercise intensity and duration. To determine whether glucocorticoid administration would alter humoral and metabolic regulation during exercise, we administered 4 mg dexamethasone (DEX) or placebo to 11 normal, moderately trained men (19-42 yr old) in a double blinded random fashion 4 h before high intensity intermittent treadmill running. Plasma levels of ACTH, cortisol, arginine vasopressin (AVP), lactate, and glucose were measured before, during, and after exercise. A wide range of ACTH responses were seen in the DEX-treated group and arbitrarily defined as two subsets of individuals according to their responses to dexamethasone: DEX nonsuppressors and DEX suppressors. Exercise-induced increases in heart rate and circulating concentrations of cortisol, AVP, lactate, and glucose were all significantly greater (P < 0.05) in nonsuppressors (n = 4) compared to suppressors (n = 7) after both placebo and DEX administration. Interestingly, heart rate, AVP, and lactate responses were unaltered by DEX alone in both groups. In summary, this study demonstrates that normal individuals exhibit differential neuroendocrine and metabolic responses to exercise and pituitary/adrenal suppression after pretreatment with DEX. These findings reflect marked individual differences in the stress response to exercise that may derive from or lead to differential glucocorticoid negative feedback sensitivity in humans.     

alpha-Melanocyte stimulating hormone inhibits tumour necrosis factor-alpha stimulated intercellular adhesion molecule-1 expression in normal cutaneous human melanocytes and in melanoma cell lines

alpha-Melanocyte stimulating hormone (alpha-MSH) was found significantly to reduce tumour necrosis factor-alpha (TNF-alpha) stimulated upregulation of intercellular adhesion molecule-1 (ICAM-1) in normal adult cutaneous melanocytes. The maximum inhibitory response to alpha-MSH was obtained at around 10(-10) mol/L alpha-MSH when cells were coincubated with alpha-MSH and TNF-alpha for 24 h. alpha-MSH had little or no effect on basal ICAM-1 expression in melanocytes and the effects of alpha-MSH could be mimicked with 3-isobutyl-1-methylxanthine (IBMX). Preliminary data in three human melanoma cell lines also showed alpha-MSH and forskolin to be effective in significantly reducing TNF-alpha stimulated ICAM-1 expression over 24 h. The extent of the inhibition varied from cell line to cell line and was greatest in those cells with the highest number of alpha-MSH receptors. These data suggest that alpha-MSH has the ability to oppose the action of the pro-inflammatory cytokine TNF-alpha on melanocytes and melanoma cells.