Symptomatic and functional outcome of surgical treatment of cervical dystonia

OBJECTIVES: Previous studies of surgical treatment for cervical dystonia have reported highly variable rates of postoperative symptomatic benefit and morbidity. Little is known about functional improvement and long term results. This study evaluates the symptomatic and functional outcome of surgical treatment of cervical dystonia in a consecutive series of 46 patients. METHODS: The most affected muscles were selected for denervation after clinical examination and confirmation by four channel EMG studies. Surgical treatment, aiming at selective elimination of pathological activity while preserving normal motor function and avoiding side effects, was achieved by using a broad scope of techniques including intradural denervation, extradural denervation, and myotomy. Rather than carrying out standard operations, the treatment was tailored to the needs of the patient according to the individual pattern of dystonic activity. Long term benefit was assessed with a global outcome score, and a modified Toronto western spasmodic torticollis rating scale (TWSTRS) in those 34 patients who were available for a recent follow up evaluation. RESULTS: The 46 patients underwent a total of 70 procedures with intradural approaches in 33 instances, extradural approaches in 21, and muscle sections (singly or combined) in 22 instances. Transient mild postoperative side effects occurred in 10% of the procedures. The mean duration of long term follow up was 6.5 years. The global outcome was rated as excellent in nine patients (21%), as marked in 12 (27%), as moderate in nine (21%), as mild in nine (21%), and as no improvement in five (11%). A persistent side effect consisting of mild difficulty with balance was noted in one case. There were highly significant changes of the preoperative and postoperative mean values for almost all TWSTRS subscores for severity of cervical dystonia, functional disability, and pain. Patients with excellent outcome underwent a higher number of surgical procedures on average than those patients who achieved no benefit. CONCLUSIONS: Surgical treatment tailored to the specific pattern of dystonic activity in the individual patient is a valuable alternative in the long term management of cervical dystonia.     

Improved quantitation of minimal residual disease in multiple myeloma using real-time polymerase chain reaction and plasmid-DNA complementarity determining region III standards

The complementarity determining region III of the rearranged immunoglobulin heavy chain gene has been the target for tumor-specific PCR assays for the detection and follow-up of B-cell malignancies. Previously, these assays have relied on gel-based end point data collection methods (i.e., band densitometry) and, thus, have provided at best a semiquantitative assessment of tumor levels. We show the development of a novel, real-time TaqMan PCR assay to quantitate residual multiple myeloma cells in clinical samples after high-dose chemotherapy and autologous stem cell transplantation. We provide evidence that real-time PCR is reproducible, sensitive, and quantitative. In a 40-replicate PCR experiment targeting the beta-actin gene, the coefficient of variation for threshold cycle data was 1.6%, whereas it increased to 13.6% and 31%, respectively, for end point fluorescence and gel densitometry. Moreover, in an experiment directly comparing standard curves obtained from band densitometry and threshold cycle data, the standard curve constructed from threshold cycle data had a multiple R2 value of 1.00 and demonstrated a dynamic range >4 logs, compared with the 2-log linear range of gel densitometry. Finally, we show that when a complementarity determining region III-specific PCR primer is used in conjunction with a consensus primer for the immunoglobulin heavy chain joining gene, plasmid DNA can be used as a readily available and effective substitute for clonal plasma-cell genomic DNA when preparing standards. By applying real-time PCR to the analysis of clinical samples, we are able to quantitate levels of tumor involvement with unparalleled reproducibility and statistical confidence. Real-time PCR technology may well provide the accuracy and reliability necessary for minimal residual disease detection to have real prognostic significance.     

Use of bedside activated partial thromboplastin time monitor to adjust heparin dosing after thrombolysis for acute myocardial infarction: results of GUSTO-I. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries

Multiple five-day testing of rats in the open field and elevated plus-maze revealed a regressive dynamics of the integral characteristics of the exploratory behavior. The integral quantitative indices of searching activity in Henderson's test of extrapolation deliverance (modified by N. A. Bondarenko) and in active shock avoidance in N. R. Grigor'ev's problem box, on the contrary, displayed a progressive dynamics, like quantitative characteristics of cognitive activity. We established the differences between the determinants and control mechanisms of exploratory behavior and searching activity. This allowed us to differentiate these forms of behavior as different functional states.     

Immunoglobulin A in saliva of children: age dependence and effect of respiratory tract diseases

Immunoglobulin A (IgA) plays an essential role in the local defence mechanism and is part of the immunologic system. It is transported to the endothelial surface either as a monomer or as a dimer of two molecules of IgA connected by a j-chain and attached to a secretory component. The aim of the present study was to assess the relation of salivary IgA to the age of children and to assess a possible influence by acute and chronic respiratory diseases. IgA was measured in the saliva of altogether 230 children by means of radial immunodiffusion (LC-IgA Partigen, Behring) following a standardised protocol. Relation to age was measured in 159 healthy children aged one month to 15 years. The median of IgA was 36 mg/l with a range of 3.5-291 mg/l. There was no statistically significant relationship between salivary IgA and the age of the children. Median IgA in the saliva of children without any respiratory disorders (n = 169) was 36 mg/l (3.5-291 mg/l), of children with acute respiratory diseases (n = 33) 51 mg/l (3.5-257 mg/l) and of children with chronic respiratory diseases (n = 28) 47 mg/l (3.5-165 mg/l). There was no statistically significant difference between these three groups. In conclusion, the results of this study show that IgA in the saliva of children may not be related to age or influenced by acute or chronic respiratory diseases.     

Alternate iron transport pathway. Mobilferrin and integrin in K562 cells

A transferrin-independent iron transport system in cells containing transferrin receptors was described previously by several investigators. Prior studies did not identify the proteins involved in this alternate iron transport pathway. Using a human-derived erythroleukemia tissue culture line, iron-binding proteins were isolated from cytosol and cell membranes. The cytosol protein was soluble in 60% ammonium sulfate, had a molecular mass similar to mobilferrin (56 kDa), and reacted with anti-mobilferrin antibodies. The water-insoluble radiolabeled protein was solubilized with Nonidet P-40 and immunoprecipitated with monoclonal antibody against beta 3 human integrin. Pulse-chase studies suggested sequential passage of iron to integrin, mobilferrin, and ferritin, respectively. Thus, the alternate iron transport pathway contained proteins similar to those observed in intestinal cells which did not possess transferrin receptors on their absorptive surface. The alternate iron transport pathway is only partially shared with zinc and cadmium. Mobilferrin bound zinc and iron competitively, but the two metals were not transported competitively into K562 cells. Immunoprecipitates of integrin containing radiozinc were obtained with a monoclonal antibody against beta 1 human integrin. This suggested iron and zinc may utilize different integrins to passage the cell membrane.