Failure of bone induction by bone matrix in adult monkeys

Extraskeletal bone formation can be induced in rodents by implantation of demineralised bone matrix and such implantation has been used to treat bone defects in man, but it is uncertain if induction or merely conduction occurs. We studied bone induction in primates by excising segments of the fibulae of adult squirrel monkeys, defatting and demineralising them before reimplanting them into the quadriceps of the same animal. As a control experiment, rat matrix was prepared in exactly the same way and implanted in rats. After six weeks the implants were harvested and either ashed and analysed for calcium content or prepared for histology. In the rats, the calcium content indicated that about 20% of the original matrix had been replaced by new bone. In the monkeys the calcium content was about the same as that in normal body fluid and no bone was seen in histological sections. This result casts doubt on the use of demineralised human bone matrix as a bone inductor, although it may function by other mechanisms.     

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (UPDRS), known as the MDS-UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinson's disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS-UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1-day face-to-face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS-UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS-UPDRS in order to increase uniform usage. Multiple language editions are planned. A three-part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.     

Novel molecular aspects of prostate carcinogenesis.

Prostate adenocarcinoma is one of the most frequently diagnosed forms of cancer in the male population of the Western world. The pivotal role of androgen and its receptor in this disease has been abundantly documented and indeed, chemical castration and treatment with antiandrogens are now standard therapies. However, relapse is often observed after 18-24 months, due to the remarkable ability of prostate tumour cells to adapt to low or undetectable androgen levels. Amplification and mutations of the androgen receptor (AR) gene have been described as well as alterations in cofactor expression and crosstalk with other signalling pathways. Another recent line of research focused on the re-programming of gene expression taking place in prostate tumours. Global expression profiling of normal and cancerous prostate tissues led to the identification of tumour-distinctive patterns. Validation studies are currently underway to identify novel drug targets as well as diagnostic and outcome prediction markers.     

Influence on the masticatory system in treatment of obstructive sleep apnea and snoring with a mandibular protruding device: A 2-year follow-up

The aim was to identify the incidence and types of possible adverse events in the masticatory system after treatment with a mandibular protruding device (MPD) during a 2-year period in patients with obstructive sleep apnea (OSA) or snoring. The subjects comprised 65 middle-aged patients (44 OSA patients, 21 snorers). A clinical examination and a questionnaire concerning signs and symptoms from the masticatory system were performed before, after 6 months, and after 2 years of MPD use. The frequencies of registered signs from the masticatory system, such as muscle and joint tenderness, palpation, and pain during mandibular movement, decreased significantly between baseline and the 2-year follow-up. There were significant changes in the mandibular range of protrusion (+0.7 mm, P < .001), overjet (-0.5 mm, P < .001), and overbite (-0.6 mm, P < .001) compared with the initial examination. Nine patients developed a lateral open bite during treatment, and 2 of them experienced subjective symptoms related to the altered occlusion but still used the MPD every night. No patient reported pain on opening the mouth wide or during jaw movements. Two reported tiredness on jaw function. The reported frequency of headaches was also significantly reduced (P < .01). The high compliance rate in MPD use showed that the therapy is well tolerated, but there is a risk of minor alterations in the occlusion during MPD treatment.     

Proteoglycan fragments in knee joint fluid after exercise

The concentration of cartilage proteoglycan fragments in knee joint fluid was measured before and after one event of physical exercise in 33 healthy athletes. Nine athletes ran on a treadmill for 60 min, 16 ran on road for 80 min and 8 played one soccer game (90 min). Before exercise, the levels of proteoglycan fragments in the athlete joint fluid were lower than in a previously analyzed reference group. After exercise, the concentration of proteoglycan fragments increased in all of the 7 athletes that could be directly compared before and after exercise. This increased concentration of proteoglycan fragments in the joint fluid could be an effect of mechanical loading of the cartilage in combination with a possible high turn-over rate of the cartilage matrix in the athletes.     

Effect of a Single Nighttime Dose of Oxazepam on Seizure Duration in Electroconvulsive Therapy

In a double-blind crossover study, 12 depressed inpatients receiving bilateral electroconvulsive therapy (ECT) were given 22.5 mg oxazepam or placebo (identical tablets, randomized order) the night before treatment. Seizure duration was measured using the cuff method and a total of 20 pairs of measurements were made. Mean duration after oxazepam administration was 0.9 s longer than after placebo; this difference was not statistically significant. The relevant lower one-sided 95% confidence limit was -4.1 s. Single administration of oxazepam, 22.5 mg, has little average effect on seizure duration in ECT.     

Incomplete effector/memory differentiation of antigen-primed CD8+ T cells in gene gun DNA-vaccinated mice

DNA vaccination is an efficient way to induce CD8+ T cell memory, but it is still unclear to what extent such memory responses afford protection in vivo. To study this, we induced CD8+ memory responses directed towards defined viral epitopes, using DNA vaccines encoding immunodominant MHC class I-restricted epitopes of lymphocytic choriomeningitis virus covalently linked to beta2-microglobulin. This vaccine construct primed for a stronger recall response than did a more conventional minigene construct. Despite this, vaccinated mice were only protected against systemic infection whereas protection against the consequences of peripheral challenge was limited. Phenotypic analysis revealed that DNA vaccine-primed CD8+ T cells in uninfected mice differed from virus-primed CD8+ T cells particularly regarding expression of very-late antigen (VLA)-4, an adhesion molecule important for targeting T cells to inflammatory sites. Thus, our DNA vaccine induces a long-lived memory CD8+ T cell population that provides efficient protection against high-dose systemic infection. However, viral replication in solid non-lymphoid organs is not curtailed sufficiently fast to prevent significant virus-induced inflammation. Our results suggest that this is due to qualitative limitations of the primed CD8+ T cells.     

Evaluation of Etest MBL for detection of blaIMP-1 and blaVIM-2 allele-positive clinical isolates of Pseudomonas spp. and Acinetobacter spp

The Etest MBL (AB BIODISK, Solna, Sweden) correctly differentiated all 57 isolates of Acinetobacter spp. and Pseudomonas aeruginosa with the bla(IMP-1) allele and 135 of 137 (98.5%) Acinetobacter spp. and Pseudomonas spp. isolates with the bla(VIM-2) allele. The Etest MBL was reliable for detecting the IMP-1- and VIM-2-producing Pseudomonas and Acinetobacter isolates.