An automatic algorithm for stationary segmentation of extracellular microelectrode recordings.

Extracellular microelectrode recordings (MER) often contain artifact from a variety of sources that confound traditional signal-processing techniques that require stationary signal segments. We designed an algorithm to locate the longest stationary segment of MER signals. In this paper we provide a description of the segmentation algorithm and its performance assessment. Simulation results demonstrate that the automatic segmentation algorithm we proposed is capable of accurately identifying the boundaries of the longest stationary segments in MER signals. In our simulation study the segmentation algorithm correctly identified the boundaries of the longest MER stationary segments in 99.5% of the cases.

Plasma concentrations of N-terminal brain natriuretic peptide in healthy children, adolescents, and young adults: effect of age and gender.

Children with congenital heart disease need adequate diagnostic classification regarding their cardiovascular status (CVS). N-terminal brain natriuretic peptide (N-BNP) plasma concentration indicates dysfunction of the cardiovascular system and guides decisions concerning treatment and prognosis. Reference values are established for adults, with age-dependent increasing values and higher values in women. To avoid misclassification concerning the CVS, a large group of healthy children and adolescents can be used show the relationship between gender, age, and N-BNP and these can serve as reference values. N-BNP was measured in 434 healthy subjects (240 female and 194 male) with ages ranging from 0 to 32 years without any cardiovascular disease or renal or hepatic impairment. Measurements were performed with an electrochemiluminescence immunoassay from Roche Diagnostics. Mean N-BNP decreased from 12.6 fmol/ml (0-9 years; n = 79) to 9.41 fmol/ml (10-14 years; n = 154) and in adolescents from 6.1 (15-19 years; n = 99) to 4.8 fmol/ml (> 19 years; n = 102) in adults (p < 0.05). Mean N-BNP concerning gender did not differ in any age group younger than 19 years. In contrast, the adult female group had 78% higher N-BNP compared to the male group (p < 0.05). There was a significant peak in N-BNP at the age of 12-14 years. This study shows that reference values for N-BNP differed profoundly in children compared to adults and were up to 260% higher in children without any gender difference. Therefore, these reference values will help to avoid CVS misclassification in children for the biomarker N-BNP.

Stimulated muscle force assessment of the sternocleidomastoid muscle in humans.

The aim of this study was to configure a force assessment device and determine potential testing protocols for quantitative evaluation of human neck muscles. The study design consisted of non-randomized control trials, with repeated measures; data from 12 normal subjects were obtained. Several apparatuses were designed, constructed and tested, i.e. single or short trains of supramaximal stimuli were used to activate sternocleidomastoid muscles in a seated position with strain gauges (6.2% variability with double-pulse stimulations) or in supine positions with load cells (5.2% variability with similar activation). Using a final configuration, maximum elicited peak forces were 1742 +/- 323 g for single-pulse and 3976 +/- 484 g for double-pulse stimulations (n = 12). There were no significant differences in maximum recorded peak torques between sessions per individual. Yet, detectable muscle activities were simultaneously recorded in the contralateral sternocleidomastoid muscles. This non-invasive, quantitative assessment approach has novel value for determining treatment efficacy, disease progression, and/or approach has novel value for determining determining treatment efficacy, disease progression, and/or relative distribution of muscle strength in patients with abnormal neck muscle function.

Surface EMG activity of the back musculature during axial spinal unloading using an LTX 3000 Lumbar Rehabilitation System.

Electromyographic (EMG) analysis has been used successfully to identify back muscle impairment in patients with low back pain. EMG signals from normal subjects during axial spinal unloading using an LTX 3000 device were obtained and spectral parameters of the electromyographic (EMG) signal were analyzed. The purpose of the study was to determine the optimal time for effective traction using the LTX 3000 rehabilitation device. These data will serve as a baseline for future studies to help assess back muscle function in low back patients undergoing rehabilitation. Three time points during axial spinal unloading were compared to pre-unloading to detect alterations in median power frequency (MPF), root-mean-square (RMS) and rectified integrated EMG (riEMG) during axial spinal unloading. There were reductions of riRMG during 0-10 minutes of axial spinal unloading in all muscle groups, followed by an increase in riEMG value from 10 to 15 minutes. A similar trend was seen in the RMS values. The MPF did not change during the course of unloading, indicating that there was likely no change in fatigue properties of the paraspinal muscles during axial spinal unloading. The optimal time for effective axial spinal unloading on the basis of muscle activity was determined to be 10 minutes of axial spinal unloading, and a back assessment procedure was presented that uses surface EMG electrodes to objectively characterize muscle activity and relative fatigue properties. Future studies will use this methodology to assess treatment outcome in a chronic low back pain population.

Physiological assessment of muscle strength in vitro after direct injection of doxorubicin into rabbit sternocleidomastoid muscle.

Doxorubicin chemomyectomy is a potent method for the permanent removal of a muscle or group of muscles after direct local injection, and has been used successfully to treat blepharospasm and hemifacial spasm patients. The efficacy of doxorubicin chemomyectomy on reducing muscle strength after direct injection of doxorubicin into rabbit sternocleidomastoid muscle was tested. One- and 6-month postinjection force assessment was performed in vitro to measure alterations in peak twitch and tetanic force generation, as well as fatigue responses for the treated muscles compared to control. There were significant reductions of both twitch and tetanic peak amplitudes in the doxorubicin-treated muscles. One month after treatment, the decreases in force were greater after 2 mg doxorubicin injections than after 1 mg doxorubicin. While there was a significant reduction in force generation after doxorubicin treatment, fatigue resistances for the doxorubicin-treated muscles were increased compared to the controls. There were significant reductions in muscle mass after doxorubicin treatment, and by 6 months, the myosin heavy chain isoform distribution was similar to normal sternocleidomastoid, except for an increase in slow myosin-positive fibers. Doxorubicin chemomyectomy resulted in a significant reduction in functional force generation in the treated sternocleidomastoid muscles. These findings suggest a potential clinical use of doxorubicin chemomyectomy to treat cervical dystonia patients.

Doxorubicin chemomyectomy as a treatment for cervical dystonia: histological assessment after direct injection into the sternocleidomastoid muscle.

The sternocleidomastoid muscle (SCM) is one of the major muscles involved in producing abnormal head position in cervical dystonia patients. This study tested whether doxorubicin chemomyectomy, direct injection of doxorubicin into the SCM to permanently remove muscle fibers, has the potential to be a nonsurgical, permanent treatment for cervical dystonia. The right SCM of rabbits was injected with either 1 or 2 mg doxorubicin. Animals were sacrificed 1-2 months postinjection. The SCM was prepared for histological examination of muscle fiber loss and fiber type composition. In all cases, direct injection of doxorubicin resulted in significant decreases in total muscle cross-sectional areas ranging from 75% up to 98%. Individual myofiber cross-sectional areas were smaller than normal after 2 mg doxorubicin treatment, but similar to normal fiber size after 1 mg doxorubicin. There were increased numbers of myofibers that expressed slow and neonatal myosin heavy chain isoforms in these remaining muscle fibers compared to the untreated SCM on the contralateral side. Developmental myosin heavy chain (MHC) was also present in 53% of the remaining myofibers of the treated muscles. The fiber type composition of muscles contralateral to the doxorubicin injections was compared to the fiber type composition of SCM from normal, untreated controls; no difference was seen in the proportions of fast, slow, and neonatal MHC fiber types in these SCM muscles. In summary, the direct injection of doxorubicin into the SCM resulted in significant muscle loss. This supports the use of doxorubicin chemomyectomy as a potential permanent, nonsurgical treatment for cervical dystonia.

Ribavirin approved with a big fat price.

AIDS: Schering-Plough has received FDA approval to market a combination of Ribavirin and Interferon-Alpha for the treatment of hepatitis C. The approval has only been granted for patients who have relapsed after previously being treated by Interferon only. The approval was granted based on two clinical trials, and the manufacturer has announced positive results from another trial that has not yet been published. Schering-Plough has applied to the FDA for expanded approval to include patients who have not been previously treated. The company's prices for the combination drug are very high, and are estimated to be 265 percent higher than prices in Mexico.^ieng

Protease inhibitors: resistance, resistance, resistance.

AIDS: Current anti-HIV drugs are plagued by problems with development of resistance. Reports at the 4th Annual Conference on Retroviruses and Opportunistic Infections proposed various ways to use protease inhibitor-containing combinations to build a high enough genetic barrier against HIV breakthrough. Two studies confirmed that potent highly active antiretroviral therapy combination therapies can be beneficial even to people with advanced AIDS and with extensive past exposure to anti-HIV therapy. While nelfinavir has shown itself to be a respectable protease inhibitor, optimum dosage questions still persist and the issue of cross-resistance is a concern. Abbott laboratories revealed its new protease inhibitor ABT-378. ABT-378 is highly active against HIV, even more so than ritonavir. Toxicity information about ABT-378 or what drug levels to use to avoid resistance are not known. Two studies that achieved some success in HIV treatment by combining protease inhibitors are also reported. Currently, there are 12 possible double protease inhibitor combinations using the three protease inhibitors on the market and nelfinavir. However, while ritonavir works with saquinavir and possibly ABT-378, there may be interference between protease inhibitors because they compete for the same binding sites on HIV protease, thus weakening the overall effect to less than the sum of their individual effects.^ieng

Dethroning AZT.

AIDS: Several trials have found that AZT added little benefit when included in two drug regimens. Human tolerance to AZT and HIV's propensity for becoming resistant to AZT are major problems. AZT remains the most prescribed HIV therapy, particularly in combination with 3TC. A popular solution for patients failing or intolerant to AZT or AZT/3TC has been d4T/3TC. AZT is known to penetrate the blood/brain barrier, thus helping to prevent or treat AIDS-related dementia. Over time, however, studies show AZT/3TC and d4T/3TC were essentially equivalent and that both should be helpful for dementia. Another study using d4T/ddI showed reduction in viral loads by 80 to 90 percent at 24 weeks, accompanied by a CD4 rise of about 40, but with significant neurological adverse effects. Combining d4T/ddI with protease inhibitors presents problems, such as a complicated dosing schedule and harsh gastrointestinal side effects. Combining hydroxyurea with d4T/ddI appears to strengthen this combination's effects. One study showed that the combination of ddI and hydroxyurea was unable to prevent the emergence of mutations that confer ddI resistance; however, the mutants were still sensitive to standard doses of ddI in the presence of hydroxyurea. One other conference report presented results of a two-arm trial comparing DuPont Merck's new DMP 266 plus indinavir to indinavir alone for 24 weeks. At trial's end, viral loads were down 2.2 logs (99.4 percent) in the indinavir arm, and CD4 counts, initially averaging 224, were up about 100 cells in both groups. The results achieved with DMP 266/indinavir rival those achieved with indinavir plus AZT/3TC or any two nucleoside analogs. DMP 266 not only is potent, but is taken only once a day.^ieng