Electrophysiological studies in a mouse model of Schwartz–Jampel syndrome demonstrate muscle fiber hyperactivity of peripheral nerve origin

Schwartz–Jampel syndrome (SJS) is an autosomal‐recessive condition characterized by muscle stiffness and chondrodysplasia. It is due to loss‐of‐function hypomorphic mutations in the HSPG2 gene that encodes for perlecan, a proteoglycan secreted into the basement membrane. The origin of muscle stiffness in SJS is debated. To resolve this issue, we performed an electrophysiological investigation of an SJS mouse model with a missense mutation in the HSPG2 gene. Compound muscle action potential amplitudes, distal motor latencies, repetitive nerve stimulation tests, and sensory nerve conduction velocities of SJS mice were normal. On electromyography (EMG), neuromyotonic discharges, that is, bursts of motor unit action potentials firing at high rates (120–300 HZ ), were constantly observed in SJS mice in all muscles, except in the diaphragm. Neuromyotonic discharges were not influenced by general anesthesia and disappeared with curare administration. They persisted after complete motor nerve section, terminating only with Wallerian degeneration. These results demonstrate that perlecan deficiency in SJS provokes a neuromyotonic syndrome. The findings further suggest a distal axonal localization of the generator of neuromyotonic discharges. SJS should now be considered as an inherited disorder with peripheral nerve hyperexcitability. Muscle Nerve, 2009     

Salvage Therapy with Methyl-gag, High-Dose Ara-C, M-Amsa, and Ifosfamide (MAMI) for Recurrent or Refractory Lymphoma

Thirty adult patients with relapsed or refractory malignant lymphoma underwent a Phase I-II trial of salvage chemotherapy combining methyl-gag, high-dose Ara-C, M-Amsa, and ifosfamide (MAMI protocol). All patients had been extensively pretreated. At the time of salvage therapy, 21 patients had visceral involvement and 23 patients were refractory. The overall response rate was 50% (11 patients in complete remission and 3 patients in partial remission). The main toxicity was myelosuppression; 4 treatment-related deaths occurred and 17 patients died of tumor progression with a median of 5 months. The MAMI protocol showed similar antitumoral efficacy to that of other salvage chemotherapy regimens used for poor prognosis malignant lymphoma but was more toxic. However, a response rate of 45 % in refractory patients should be taken into account and this drug association deserves further investigation with regard to the selection of patients for bone marrow transplants.     

Dosimetric Quality Assurance for Intensity–Modulated Radiotherapy Feasibility Study for a Filmless Approach

Purpose:  

Test and comparison of various 2–D real–time detectors for dosimetric quality assurance (QA) of intensity–modulated radiotherapy (IMRT) with the vision to replace radiographic films for 2–D dosimetry.     

Effect of Clarithromycin on Inflammatory Markers in Patients with Atherosclerosis

Atherosclerosis can to a certain extent be regarded as an inflammatory disease. Also, inflammatory markers may provide information about cardiovascular risk. Whether macrolide antibiotics, especially clarithromycin, have an anti-inflammatory effect in patients with atherosclerosis is not exactly known. To study this phenomenon, a placebo-controlled, randomized, double-blind study was performed. A total of 231 patients with documented coronary artery disease received a daily dose of either 500 mg of slow-release clarithromycin or placebo until the day of surgery. Levels of inflammatory markers (C-reactive protein, interleukin-2 receptor [IL-2R], IL-6, IL-8, and tumor necrosis factor alpha) were assessed during the preoperative outpatient visit, on the day of surgery, and 8 weeks after surgery. Also, changes in the levels of inflammatory markers between visits were determined by delta calculations. Baseline patient characteristics were balanced between the two treatment groups: the average age was 66 years (standard deviation [SD] = 9.0), 79% of the patients were male, and the average number of tablets used was 16 (SD = 9.3). The inflammatory markers of the groups as well as the delta calculations were not significantly changed. Treatment with clarithromycin did not influence the inflammatory markers in patients with atherosclerosis.     

Effects of Antidepressants on G Protein-coupled Receptor Signaling and Viability in Xenopus laevis Oocytes

Background: Tricyclic antidepressants are structurally related to local anesthetics, suggesting that part of their analgesic action may result from properties shared with local anesthetics. Because local anesthetics block G protein-coupled receptor signaling (which explains, in part, their inflammatory modulating properties), the authors studied whether antidepressants have similar effects.

Methods: Peak Ca-activated Cl currents induced in Xenopus laevis oocytes by lysophosphatidic acid (10-4 m) were measured using a voltage clamp. The effects of a 30-, 120-, or 240-min incubation in amitriptyline, nortriptyline, imipramine, or fluoxetine were determined.

Results: After a 30-min incubation, low concentrations (10-7-10-5 m) of antidepressants had no effect on lysophosphatidic acid-induced currents. After prolonged incubation, only amitriptyline or nortriptyline inhibited lysophosphatidic acid signaling (each to 58% of the control response at 10-7 m after 240 min). At low concentrations, none of the compounds induced membrane damage (defined as a holding current of > 1 [mu]A, 2% in control cells). Imipramine at 10-3 m induced damage in 100% of oocytes, and fluoxetine at 10-4 m induced damage in 71% of oocytes (P < 0.05 vs. control). Amitriptyline and nortriptyline had no effect.     

Porotic hyperostosis as a marker of health and nutritional conditions during childhood: Studies at the transition between imperial rome and the early middle ages

Porotic hyperostosis, characterized by small and localized perforations on the surface of cranial bones, is considered a good indicator for assessing the health and nutritional status of past human populations. The most widely accepted theory at present indicates that anemias, either acquired or of genetic origin, are responsible for the bony lesions described as porotic hyperostosis. In this paper, the prevalence of these lesions in two skeletal samples from Latium (central Italy) was used to evaluate health and life conditions in Italy after the collapse of the Roman Empire. One sample belongs to the Roman Imperial Age (1st–3rd centuries A.D.) rural town of Lucus Feroniae; the other comes from the 7th century A.D. Lombard necropolis of Selvicciola. The prevalence of cribra orbitalia and cribra cranii was quite similar in the two samples but slightly more frequent in the Medieval community. Differential diagnosis suggested iron deficiency anemia in early childhood as the causative agent of the hyperostotic lesions in both samples. These results may be interpreted in light of previous examinations of same samples and according to their respective historical and socio‐economical characteristics. Am. J. Hum. Biol. 13:709–717, 2001. © 2001 Wiley‐Liss, Inc.