Deep brain stimulation for essential tremor

We examined the effects and safety of deep brain stimulation (DBS) as a treatment for essential tremor (ET). Ten ET patients with disabling medication-refractory tremor underwent stereotactic implantation of a DBS lead in the left Vim thalamic nucleus and completed a 6-month follow-up. The Clinical Tremor Rating Scale and disability assessments were performed at baseline, 1-, 3-, and 6-month follow-up. There were significant improvements in dressing, drinking, eating, bathing, and handwriting as reported by the subjects. Tremor severity, writing, pouring, and spiral and line drawing were significantly improved as rated by the examiner. Improvements persisted through the 6-month follow-up period. Although global disability significantly lessened in the group as a whole, one subject with hand-finger tremor accentuated by writing had no change in disability status. In this 6-month open-label study, DBS was effective and safe in reducing tremor and functional disability in ET.     

Urinary stone proteins: an update

The discovery of an organic component in kidney stones dates back to 1684. More than 150 years elapsed before the incrustation of this organic component, which is now called the matrix, was proposed as the mechanism of stone formation. The composition of the matrix remained largely unknown until the development of electron microscopy and the advances in biochemistry combined in the 1950's to usher in the modern era of renal stone matrix investigation. Composed mainly of selectively incorporated proteins generally characterized by high glutamic and aspartic acid content and the frequent occurrence of gamma-carboxyglutamic acid, the matrix displays a variable and complex composition and shares a few proteins in many stones. The embryonic stone may first appear in the renal tubules where it can acquire the blood and cell membrane proteins recently found by analysis of stone protein extracts. The combination of supersaturation, an appropriate environment, the availability of calcium binding proteins which may be abnormal, and the incorporation of proteins extracted from leukocytes and cell wall membranes may induce stone formation.     

Estimation and hypothesis testing of treatment effects in animal reproductive toxicology studies

Healy (1) and Dempster et al. (8) proposed statistical methods to evaluate the treatment effects in animal reproductive toxicology research. Both methods assume homogeneous variance for the dams and the pups, respectively, in all the treatment groups. In this paper, via mixed effect modeling, we propose a method to estimate the treatment effects allowing heterogeneous variances for the dams and the pups, respectively, in different treatment groups. Covariates will also be included in the model. A procedure to test the fixed effects is also discussed. An example from an animal reproductive toxicological study is used to illustrate the procedures.     

Tongue flicking in agamid lizards: morphology, kinematics, and muscle activity patterns

We wanted to examine whether a relation between foraging strategy, morphology, the mechanics of tongue protrusion, and prey chemical detection and discrimination exists in agamid lizards. Tongue-flick behavior was observed in two species of this family: Uromastix acanthinurus and Plocederma stellio. Potential prey chemical discrimination by means of tongue flicking was examined by using applicator tests. Tongue flicks were subsequently recorded by high-speed video in combination with the electrical activity of a number of jaw and hyolingual muscles. The kinematics of jaws and tongue and the muscle activity patterns were quantified. To investigate if the observed differences in tongue-flick behavior (mainly in the frequency of use) are translated into corresponding differences in tongue morphology, the tongues of both species were examined by light and scanning electron microscopy. The species differed mainly in the surface morphology of the foretongue and in the abundance and distribution of taste buds on the tongue and oral cavity. These differences can be related to behavioural observations; whereas U. acanthinurus readily uses tongue flicks to detect and discriminate between food items, P. stellio does not. However, differences in tongue-flick mechanics (kinematics, electromyograms) between both species were minor. Based on the data gathered in this study and from previously published data, an evolutionary transformation series leading to the complex tongue-flick cycles as observed in snakes is proposed. The required morphological and mechanical changes that accompany such an evolutionary sequence are discussed.     

Purification of a tumoral marker recognized by monoclonal antibody Po66 and associated with human lung squamous cell carcinoma

This paper reports on the production of tumor necrosis factor (TNF) and granulocyte macrophage colony-stimulating factor (GM-CSF) by cultured mononuclear adherent cells derived from bone marrow of 25 patients affected by myelodysplastic syndrome (MDS) of different FAB subtypes. Mean production of GM-CSF was much lower than in controls, without significant differences among different subtypes. Mean production of TNF was similar in MDS patients and in controls, but noteworthy differences were observed between patients with RA, RAEB and RAEB-t and patients with RARS and CMML. Growth of bone marrow granulocyte macrophage and erythroid progenitors did not correlate with TNF and GM-CSF production, although in MDS subtypes with higher GM-CSF levels, colony growth was slightly higher than in subtypes with lower GM-CSF production.     

Breast implants

We describe the case - to our knowledge unique - of an 8-year-old boy who presented with acute onset of lower cranial nerve palsy and tetraparesis caused by a hematoma in a dorsal exophytic pilocytic astrocytoma of the medulla oblongata. The boy showed near-complete recovery after neurosurgical management in two stages: first, emergency evacuation of the hematoma with tumor biopsy, and second, complete tumor removal 5 months after the initial event. Intraoperative electrophysiological monitoring techniques for the lower cranial nerves are of value in preserving their functional integrity. Ultrasonography is helpful in assessing the extent of tumor removal. Although the pathological diagnosis of a pilocytic astrocytoma would not justify radiotherapy, local field radiotherapy was added mainly because of the unexpectedly rapid tumor progression during the interval between the two surgical procedures. The literature on brainstem and tumor hematoma in children is reviewed.     

Effect of nadroparin, a low-molecular-weight heparin, on clinical and angiographic restenosis after coronary balloon angioplasty: the FACT study. Fraxiparine Angioplastie Coronaire Transluminale

BACKGROUND: Experimental studies suggest that the antiproliferative effect of heparin after arterial injury is maximized by pretreatment. No previous studies of restenosis have used a pretreatment strategy. We designed this study to determine whether treatment with nadroparin, a low-molecular-weight heparin, started 3 days before the procedure and continued for 3 months, affected angiographic restenosis or clinical outcome after coronary angioplasty. METHODS AND RESULTS: In a prospective multicenter, double-blind, randomized trial, elective coronary angioplasty was performed on 354 patients who were treated with daily subcutaneous nadroparin (0.6 mL of 10,250 anti-Xa IU/mL) or placebo injections started 3 days before angioplasty and continued for 3 months. Angiography was performed just before and immediately after angioplasty and at follow-up. The primary study end point was angiographic restenosis, assessed by quantitative coronary angiography 3 months after balloon angioplasty. Clinical follow-up was continued up to 6 months. Clinical and procedural variables and the occurrence of periprocedural complications did not differ between groups. At angiographic follow-up, the mean minimal lumen diameter and the mean residual stenosis in the nadroparin group (1.37+/-0.66 mm, 51.9+/-21.0%) did not differ from the corresponding values in the control group (1.48+/-0.59 mm, 48.8+/-18.9%). Combined major cardiac-related clinical events (death, myocardial infarction, target lesion revascularization) did not differ between groups (30.3% versus 29.6%). CONCLUSIONS: Pretreatment with the low-molecular-weight heparin nadroparin continued for 3 months after balloon angioplasty had no beneficial effect on angiographic restenosis or on adverse clinical outcomes.     

Aldosterone and dexamethasone stimulate calcineurin activity through a transcription-independent mechanism involving steroid receptor-associated heat shock proteins

1. PD 81,723 has been shown to enhance binding of adenosine to A1 receptors by stabilizing G protein-receptor coupling ('allosteric enhancement'). Evidence has been provided that in the perfused hearts and isolated atria PD 81,723 causes a sensitization to adenosine via this mechanism. 2. We have studied the effect of PD 81,723 in guinea-pig isolated atrial myocytes by use of whole-cell measurement of the muscarinic K+ current (I[K(ACh)]) activated by different Gi-coupled receptors (A1, M2, sphingolipid). PD 81,273 caused inhibition of I[K(ACh)] (IC50 approximately 5 microM) activated by either of the three receptors. Receptor-independent I[K(ACh)] in cells loaded with GTP-gamma-S and background I[K(ACh)], which contributes to the resting conductance of atrial myocytes, were equally sensitive to PD 81,723. At no combination of concentrations of adenosine and PD 81,723 could an enhancing effect be detected. 3. The compound was active from the outside only. Loading of the cells with PD 81,723 (50 microM) via the patch pipette did not affect either I[K(ACh)] or its sensitivity to adenosine. We suggest that PD 81,723 acts as an inhibitor of inward rectifying K+ channels; this is supported by the finding that ventricular I(K1), which shares a large degree of homology with the proteins (GIRK1/GIRK4) forming I[K(ACh)] but is not G protein-gated, was also blocked by this compound. 4. It is concluded that the functional effects of PD 81,723 described in the literature are not mediated by the A1 adenosine receptor-Gi-I[K(ACh)] pathway.     

Interleukin-12 induces relapse in experimental allergic encephalomyelitis in the Lewis rat

Acute, monophasic experimental allergic encephalomyelitis (EAE) in the Lewis rat shows pathological similarities to the human disease multiple sclerosis (MS). Rats that recover from EAE are essentially resistant to disease reinduction, unlike MS in which relapses are frequently associated with common bacterial and viral infections. As macrophage-derived interleukin (IL)-12 is a critical component of innate resistance to bacterial infection and appears to directly activate encephalitogenic T cells in vivo, the ability of this cytokine to reinduce paralysis in EAE was examined. Paralytic disease was exacerbated by intraperitoneal IL-12 administration and could be reinduced up to 1 week after recovery from the primary clinical episode. Concomitant with worsening of initial clinical signs and relapse was an increase in the ratio of macrophages to T cells in brain stem perivascular cuffs and the expression of inducible nitric oxide synthase in cells with both macrophage and microglial morphology. These findings suggest that IL-12 may contribute to macrophage-mediated disease exacerbation and relapse in patients with MS.