Quantification of jiggle in real electromyographic signals

Two parameters have been defined for quantifying jiggle: normalized consecutive amplitude differences (CAD) and the cross-correlational coefficient of consecutive discharges (CCC). In real recordings, artifacts from several sources may increase the variability of these parameters as they were originally defined. Two methodological modifications designed to overcome such a limitation are proposed: estimation of baseline fluctuation from segments of the recording free from nearby concurrent motor unit potentials (MUPs), and waveform alignment of consecutive discharges by correlation maximization (CM). The results obtained by the original and modified methods were compared for MUPs from normal subjects and patients with amyotrophic lateral sclerosis and chronic neurogenic diseases. With the modified method, CAD and CCC showed fewer extreme values and less scatter. The number of successfully aligned MUPs with the CM method was 18.8% higher (n = 394; Chi-square = 54.6; P < 0.001), including irregular and unstable MUPs. The proposed modifications improve our capability to quantify the jiggle of real signals and reduce the necessity of manual interventions although low-interference recordings and operator supervision are still required.     

An increased risk for non allo-immunization related intrauterine fetal death in RhD-negative patients.

OBJECTIVE: To investigate immediate perinatal outcome of RhD-negative patients carrying RhD-positive fetuses who received antenatal Rh immunoglobulin for the prevention of RhD-mediated hemolytic disease of the fetus and newborn. METHODS: A retrospective population-based analysis was conducted comparing pregnancies of all RhD-negative women who received antenatal Rh immunoglobulin prophylaxis (anti-D), to RhD-positive parturients, during the years 1988-2003. All women were RhD-negative without evidence of RhD sensitization. Patients received anti-D during the 28-30th week of pregnancy, and an additional dosage within 72 hours following delivery after confirmation of the newborn's RhD status. RESULTS: Of 145,437 deliveries during the study period, 6.8% were of RhD-negative women (n = 9961). Perinatal mortality rate was significantly higher among the RhD-negative women who received antenatal prophylaxis rhesus immunoglobulin as compared with the controls (17/1000 vs. 12/1000, OR = 1.3, 95%CI 1.2-1.6; p < 0.001). This higher mortality rate was related to a higher rate of intrauterine fetal demise (IUFD) (10/1000 vs. 6/1000, OR = 1.5, 95%CI 1.2-1.9; p < 0.001). The association remained significant after controlling for RhD isoimmunization leading to hydrops fetalis, using the Mantel-Haenszel technique (weighted OR = 1.3; 95% CI 1.1-1.5; p = 0.001). The rate of RhD isoimmunization was 0.6% (n = 58). Using a multivariable analysis with IUFD as the outcome variable, controlling for known confounders for fetal demise, RhD-negative status was an independent risk factor for IUFD. CONCLUSION: RhD-negative women carrying RhD-positive newborns are at an increased risk for IUFD despite Rh immunoprophylaxis.     

Radiation Therapy Oncology Group Phase I-II study on fast neutron teletherapy for carcinoma of the bladder

From June 1977 through March 1981, the Radiation Therapy Oncology Group sponsored a Phase I-II study (RTOG 77-05) on the use of fast neutrons for treating carcinomas of the urinary bladder. Patients entered on the study had Stage B1 (grade III or IV histology) or Stage B2, C, or D1 (any grade histology) disease. Thirteen patients received preoperative mixed-beam (neutron/photon) irradiation to 50 photon Gy-equivalent, and in 12 of these a cystectomy was performed in 4 to 6 weeks. The incidence of pathologic downstaging to Po was 58% in the cystectomy specimens. The projected survival at 30 months is 32%. Twenty-six patients were treated definitively with mixed-beam irradiation consisting of 50 photon Gy-equivalent to the pelvis followed by a 20 photon Gy-equivalent boost to the bladder itself. Eighteen of 26 patients (69%) achieved tumor clearance at some time during their follow-up but 8/18 (44%) of these ultimately exhibited some component of local failure. The projected survival at 30 months for this group of patients is 34%. However, the subset of patients with Stage B or C disease had a projected survival at 30 months of 60%. Four patients received definitive neutron irradiation alone and 3/4 achieved tumor clearance at some time during their follow-up. Actuarial curves are presented for patient survival and duration of local control, and results are compared with comparably staged patients treated with megavoltage photon irradiation. Treatment-related morbidity is also discussed.     

Neutron therapy for head and neck cancer: II. Further follow-up on the M. D. Anderson TAMVEC randomized clinical trial

Between January 1977 and February 1980, 95 patients with inoperable squamous carcinomas of the head and neck were treated in a two-armed randomized clinical trial comparing 1) mixed schedule irradiation using two neutron and three photon fractions per week and 2) standard photon irradiation. Complete tumor regression was achieved in 80% of patients treated with mixed-schedule irradiation, and in 68% of patients treated with photons. The local control rate was 44% in patients treated with mixed-schedule irradiation and 41% in patients treated with photons. There were four complications of treatment in each treatment arm. Absolute survival was 20% with mixed-schedule treatment and 17% in photons. Actuarial analysis shows superior local control and survival rates with mixed-schedule irradiation over photons only in the first two years.     

Evidence that (-)-7-hydroxy-4'-dimethylheptyl-cannabidiol activates a non-CB(1), non-CB(2), non-TRPV1 target in the mouse vas deferens

Previous experiments showed that R-(+)-WIN55212-induced inhibition of electrically-evoked contractions of mouse vasa deferentia could be antagonized by cannabidiol in a manner that appeared to be competitive but not to involve direct competition for established cannabinoid receptors. We have now discovered that (−)-7-hydroxy-4′-dimethylheptyl-cannabidiol (7-OH-DMH-CBD) inhibits electrically-evoked contractions of the vas deferens (EC₅₀ = 13.3 nM). This it appeared to do by acting on prejunctional neurones as 100 nM 7-OH-DMH-CBD did not attenuate contractile responses to phenylephrine or β,γ-methylene-ATP. Although 7-OH-DMH-CBD was antagonized by SR141716A, it was less susceptible to antagonism by this CB₁ receptor antagonist than R-(+)-WIN55212. 7-OH-DMH-CBD was also antagonized by cannabidiol (1 μM; apparent K_B = 222.2 nM) but not by the CB₂ receptor antagonist, SR144528 (32 nM), or by naloxone (300 nM), ruthenium red (1 μM) or capsazepine (10 μM). Yohimbine (100 nM) enhanced the ability of 7-OH-DMH-CBD to inhibit electrically-evoked contractions. R-(+)-WIN55212 was also potentiated by 100 nM yohimbine, possibly reflecting ongoing sequestration of G_i/o proteins from CB₁ receptors by ₂-adrenoceptors. Our results suggest that 7-OH-DMH-CBD may activate a neuronal target in the vas deferens that is not a CB₁, CB₂, TRPV1, opioid or ₂-adrenergic receptor but do not exclude the possibility that it also activates CB₁ receptors.     

Low-energy laser irradiation promotes cellular redox activity

Low-energy visible light (LEVL) has been shown to stimulate cell functions. This is called "photobiostimulation" and has been used successfully over the last three decades for treating a range of conditions, including soft tissue injuries, severe wounds, chronic pain, and more. Nevertheless, the mechanism of photobiostimulative processes is still being debated. It is obvious that, in order to interact with the living cell, light has to be absorbed by intracellular chromophores. In a search for chromophores responsible for photobiostimulation, endogenous porphyrins, mitochondrial and membranal cytochromes, and flavoproteins were found to be suitable candidates. The above-mentioned chromophores are photosensitizers that generate reactive oxygen species (ROS) following irradiation. As the cellular redox state has a key role in maintaining the viability of the cell, changes in ROS may play a significant role in cell activation. In the present review, we summarize evidence demonstrating that various ROS and antioxidants are produced following LEVL illumination. We found that very little evidence for NO formation in illuminated non-vascular smooth muscle cells exists in the literature. We suggest that the change in the cellular redox state which plays a pivotal role in maintaining cellular activities leads to photobiostimulative processes.     

Pick bodies in a family with presenilin-1 Alzheimer's disease

Presenilin-1 (PS-1) mutations can cause Pick's disease without evidence of Alzheimer's disease (AD). We describe a family with a PS-1 M146L mutation and both Pick bodies and AD. Sarkosyl-insoluble hyperphosphorylated tau showed three bands consistent with AD, although dephosphorylation showed primarily three-repeat isoforms. M146L mutant PS-1 may predispose to both Pick's disease and AD by affecting multiple intracellular pathways involving tau phosphorylation and amyloid metabolism.