Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up

By using stereotaxic surgical techniques, ventral mesencephalic tissues from aborted human fetuses of 8 to 10 weeks' gestational age were implanted unilaterally into the striata in two patients with advanced Parkinson's disease. The patients were treated with a cyclosporine, azathioprine, and steroid regimen to minimize the risk for graft rejection. They were examined for 6 months preoperatively and 6 months postoperatively and continued to receive the same doses of antiparkinsonian medication. There were no significant postoperative complications. No major therapeutic effect from the operation was observed. However, in the clinical tests, both patients showed small but significant increases of movement speed for repeated pronation-supination, fist clenching, and foot lifting. The rate of walking also increased in the one patient tested. For both patients, there was an initial worsening postoperatively, followed by improvement vs preoperative performance at 1 to 3 months. Both patients also showed significant improvement in the magnitude of response to a single dose of levodopa (L-dopa), but there was no increase in the duration of drug action. The motor readiness potential increased in both patients postoperatively, primarily over the operated hemisphere. Neurophysiological measurements also showed a more rapid performance of simple and complex arm and hand movements on the side contralateral to transplantation in one patient at 5 months postoperatively. Positron emission tomography demonstrated no increased uptake of 6-L-(18F)-fluorodopa in the transplanted striatum at 5 and 6 months. Taken together, these results suggest that the fetal nigral implants may have provided a modest improvement in motor function, consistent with the presence of small surviving grafts. Although our results support further scientific experimentation with transplantation in Parkinson's disease, widespread clinical trials with this procedure are probably not warranted at this time.     

Exploring Theta Burst Stimulation as an intervention to improve motor recovery in chronic stroke.

OBJECTIVE: To explore the effects of a single session of repetitive Transcranial Magnetic Stimulation, given as Theta Burst Stimulation, on behavioural and physiological measures of hand function in chronic stroke patients. METHODS: Six chronic stroke patients with incomplete recovery of the hand were tested under three conditions: excitatory TBS over the stroke hemisphere (iTBS(SH)), inhibitory TBS (cTBS(IH)) over the intact hemisphere and sham stimulation. Behavioural outcomes included simple and choice reaction time paradigms. Physiological effects were assessed using single pulse TMS on both sides. Changes were sought for up to 40min after TBS. RESULTS: Immediately after iTBS(SH) simple reaction times in the paretic hands were decreased and, compared to sham stimulation, remained significantly shorter throughout the testing period. The amplitude of the MEPs at rest and during background contraction and the area under the Input-Output curves were also increased on the stroke side after iTBS(SH). cTBS(IH) suppressed the MEPs evoked in the healthy hands but did not change motor behaviour or the electrophysiology of the paretic hands. No side effects were encountered. CONCLUSIONS: TBS seems safe in chronic stroke patients. iTBS over the stroke hemisphere transiently improved motor behaviour and corticospinal output in the paretic hands. SIGNIFICANCE: Excitatory TBS may represent a useful rTMS protocol to apply to the stroke hemisphere in future longer term therapy trials.     

Anulus fibrosus in bulging intervertebral disks

In this investigation the association of radial tears of the anulus fibrosus and bulging of the intervertebral disk was studied. An index of disk bulging was measured in sagittal anatomic sections in 149 lumbar disks from 31 cadavers. The indexes of disk bulging were correlated with stages of disk development and the presence of an annular tear. The largest disk-bulging indexes were always associated with radial tears of the anulus. Eighty-four percent of the disks with radial tears had disk-bulging indexes greater than 2.5 mm. Most normal adult disks had an index of less than 2.5 mm. The results challenge the concept that the anulus fibrosus is intact in bulging disks, although ruptured in herniated disks.     

How brief is solution focussed brief therapy? a comparative study

Solution Focused Brief Therapy (SFBT) focuses on clients' strengths and expressed goals in an attempt to produce therapeutic change as quickly as possible. This study examined whether clients seen for SFBT were seen for fewer sessions than those seen for cognitive behaviour therapy (CBT) in a clinical psychology service taking adult referrals from primary care. The study was a retrospective one using pseudo-randomization. The results indicated that SFBT clients (n = 41) were seen for two sessions on average compared to five for CBT (n = 119). This difference was accounted for by a higher proportion of the SFBT group being seen for one session only, which is consistent with the approach. A simple therapist-rated outcome scale showed no significant difference between the two groups. Copyright © 2005 John Wiley & Sons, Ltd.     

The role of TNF-alpha in fever: opposing actions of human and murine TNF-alpha and interactions with IL-beta in the rat.

1. The role of tumour necrosis factor-alpha (TNF-alpha) in fever is controversial. Some studies have indicated that TNF-alpha acts as a cryogen to inhibit fever, while others suggest that TNF-alpha is an endogenous pyrogen which mediates fever. The majority of studies in experimental animals supporting a cryogenic action have been conducted using human (h)TNF-alpha, which has been shown to bind only to one (p55) of the two TNF-alpha receptors in rodents. 2. The aim of the present investigation was to study the role of TNF-alpha in fever by comparing effects of hTNF-alpha, which binds only to the p55 receptor, with those of murine (m) TNF-alpha, which binds to both p55 and p75 TNF-alpha receptors, and to investigate the relationship between TNF-alpha and interleukin-1 (IL-1), an important endogenous pyrogen. 3. Injection of hTNF-alpha (0.3-10 micrograms kg-1, i.p.) had no effect on core temperature in conscious rats (measured by remote radiotelemetry), whereas mTNF-alpha (3 micrograms kg-1) induced fever which was maximal 1 h after the injection (38.2 +/- 0.2 degrees C compared to 37.3 +/- 0.1 degrees C in controls). Intracerebroventricular (i.c.v.) administration of either form of TNF-alpha elicited dose-dependent fever at doses higher than 0.12 microgram kg-1. 4. Peripheral injection of hIL-1 beta (1 microgram kg-1) resulted in fever (38.3 +/- 0.2 degree C compared to 37.2 +/- 0.1 degrees C in controls at 2 h), which was significantly attenuated (P < 0.01) by co-administration of a sub-pyrogenic dose of hTNF-alpha (1 microgram kg-1), but was unaffected by co-administration of mTNF-alpha (0.1 or 0.3 microgram kg-1, i.p.). In contrast, intracerebroventricular (i.c.v.) co-administration of a sub-pyrogenic dose (0.12 microgram kg-1) of hTNF-alpha did not attenuate fever induced by intraperitoneal (i.p.) injection of IL-1 beta, and sub-pyrogenic dose (0.12 microgram kg-1, i.c.v.) of mTNF-alpha significantly prolonged the febrile response to IL-1 beta. Pretreatment of animals with anti-TNF-alpha antiserum (i.c.v.) did not affect the febrile response to systemic IL-1 beta. 5. Animals injected i.p. with a pyrogenic dose of mTNF-alpha developed fever (38.2 +/- 0.2 degrees C compared to 37.3 +/- 0.1 degrees C in controls 2 h after the injection) that was completely abolished by peripheral administration of IL-1ra (2 mg kg-1, P < 0.001), while i.c.v. administration of IL-1ra (400 micrograms/rat) did not affect mTNF-alpha-induced fever. 6. These data indicate that endogenous TNF-alpha is probably a pyrogen and that previous results suggesting cryogenic actions of TNF-alpha resulted from the use of a heterologous protein in the rat. The markedly contrasting effects of mTNF-alpha and TNF-alpha could result from different interactions with the two TNF-alpha receptor subtypes. The data also suggest that fever induced by exogenous TNF-alpha is mediated via release of IL-1 beta in peripheral tissues, but not in the brain.     

Bilaterally coherent tremor resembling enhanced physiological tremor: report of three cases.

The contribution of the central nervous system to tremor pathogenesis is unclear. Poor side-to-side coherence in physiological, essential, and parkinsonian tremors suggests distinct bilateral generators. By contrast, significant bilateral coherence demonstrated in orthostatic tremor and in enhanced physiological tremor (EPT) in patients with persistent mirror movements favours single or closely linked bilateral oscillators. We describe three patients (aged 21-37 years) who developed unusual bilateral postural and kinetic tremors at 6-13 Hz resembling EPT. The tremor involved all limbs, and in two cases the face or jaw, in the absence of other significant neurological features. Significant side-to-side coherence was demonstrated in each case using cross-correlation of electromyographic recordings from homologous muscle pairs. We postulate that these unusual tremors originate from a single brainstem source or from bilateral oscillators closely linked at or below this level.     

The role of brown fat in diet-induced thermogenesis

Laboratory rodents can be induced to overeat voluntarily when exposed to a choice of highly palatable human foods so-called "cafeteria diet". The hyperphagia of these animals is associated with marked increases in energy expenditure and reduced levels of energetic efficiency. Increases in Diet-Induced-Thermogenesis (DIT) in response to overfeeding have been demonstrated in several species including man. The studies with the cafeteria-fed rats confirm the large potential for DIT in young animals. In older (26-week-old rats) a dramatic decline in the capacity for DIT is observed. Increases in energy expenditure resulting from hyperphagia appear to be mediated by the sympathetic nervous system, which causes activation of heat production in brown adipose tissue (BAT). The high thermogenic potential of BAT is due to the physiological uncoupling of oxidative phosphorylation in the inner mitochondrial membrane. This activity is enhanced by overfeeding, which causes hypertrophy. DIT and BAT are controlled by hormonal action: noradrenaline appears to be the primary activator of BAT and insulin may be required for DIT and may even activate thermogenesis. Other hormones such as glucagon, thyroid, melatonin, TSH, endorphins and sex hormones are also implicated in one way or another in the regulation of energy balance and the control of thermogenesis.