Late denervation in patients with antecedent paralytic poliomyelitis

The development of new weakness, fatigue, and pain decades after acute paralytic poliomyelitis is a recognized syndrome. We conducted a controlled study of this syndrome by analyzing clinical, electromyographic, and muscle-biopsy features in 18 patients with a history of poliomyelitis--13 reporting 1 to 20 years of new weakness and 5 without new symptoms. The patients with new weakness also reported new muscle atrophy (9 of 13) and fatigue (10 of 13), symptoms not reported by the controls. The age at the time of acute poliomyelitis, severity of poliomyelitis, residual disability, number of years since acute poliomyelitis, and age at the time of study were comparable in the weakening and control groups. Evidence of remote denervation consistent with antecedent poliomyelitis was demonstrated in all patients by electromyography or muscle biopsy or both. In addition, active denervation (as evidenced by spontaneous activity on conventional electromyography, increased jitter on single-fiber electromyography, or atrophic myofibers) was found in 12 patients in the weakening group and in all 5 controls. Immunohistochemical detection of myofibers expressing the neural-cell adhesion molecule corroborated ongoing denervation in both patient groups. When muscle data from both groups were pooled, correlations were observed between the extent of past reinnervation and the degree of ongoing motor-unit instability. We conclude that the extensive reinnervation of denervated muscle that occurs in paralytic poliomyelitis may be followed by late denervation of the previously reinnervated muscle fibers. Electromyographic and muscle-biopsy evidence of ongoing denervation does not distinguish between stable patients with prior paralytic poliomyelitis and those with new weakness.     

The plasminogen activation system reduces fibrosis in the lung by a hepatocyte growth factor-dependent mechanism

Mice deficient in the plasminogen activator inhibitor-1 gene (PAI-1-/- mice) are relatively protected from developing pulmonary fibrosis from bleomycin administration. We hypothesized that one of the protective mechanisms may be the ability of the plasminogen system to enhance hepatocyte growth factor (HGF) effects, which have been reported to be anti-fibrotic in the lung. HGF is known to be sequestered in tissues by binding to extracellular matrix components. Following bleomycin administration, we found that HGF protein levels were higher in bronchoalveolar lavage fluid from PAI-1-/- mice compared to wild-type (PAI-1+/+) mice. This increase could be suppressed by administering tranexamic acid, which inhibits plasmin activity. Conversely, intratracheal instillation of urokinase into bleomycin-injured PAI-1+/+ mice to activate plasminogen caused a significant increase in HGF within bronchoalveolar lavage and caused less collagen accumulation in the lungs. Administration of an anti-HGF neutralizing antibody markedly increased collagen accumulation in the lungs of bleomycin-injured PAI-1-/- mice. These results support the hypothesis that increasing the availability of HGF, possibly by enhancing its release from extracellular matrix by a plasmin-dependent mechanism, is an important means by which activation of the plasminogen system can limit pulmonary fibrosis.     

Perceptual distortion of face deletion by local anaesthesia of the human lips and teeth

As visual guidance of facial movements is impossible, accurate movements for speech and mastication require an established body image that is formed via the information from mechanoreceptors in the skin, mucosa, periodontium, and proprioceptors in the facial and masticatory muscles and in the jaw joints. In this study we aimed to investigate how the acute deafferentation of lips and teeth alters the established image of lips, teeth and the thumb. We used a psychophysical method to determine whether the perceived sizes of the upper lip and front teeth change when the sensory input from the lips and front teeth is fully blocked. We also examined the perceived size of the thumb to test for acute interactions between the thumb and facial structures. Local anaesthetic blocking of upper lip and upper front teeth significantly increased the perceived size of the upper lip by as much as 100% (range 21–100%) in ten out of eleven subjects tested (overall mean 52%; p=0.001). The perceived size of the upper teeth also significantly increased by as much as 155% (range 30–155%) in eight of the eleven subjects during anaesthesia (overall mean 41%; p=0.035). When the region of anaesthesia was increased and both upper and lower teeth and lips were anaesthetised, the perceived size of the upper lip again increased, by 53% (p=0.040), but the change in perceived size of the upper front teeth (18%) was not significant (p=0.206). In both studies there was no change in perceived size of the thumb. The results illustrate the labile central interaction between sensory inputs and the importance of feedback from peripheral afferents in generating the subjective facial image. The timing, level, and area of anaesthesia may be important modifiers of these interactions.     

Das Volumen,die Volumendehnbarkeit und die Druck-Längen-Beziehungen des gesamten aortalen Windkessels in Abhängigkeit von Alter,Hochdruck und Arteriosklerose

Zusammenfassung An Hand von 52 Aorten, die durch Unterbindung sämtlicher Äste abgedichtet werden konnten, wurde dasAorten-Fassungsvermögen von der Geburt an bis in das höhere Lebensalter bei verschiedenen Füllungsdrucken festgestellt undmit den Volumina des arteriellen Windkessels verglichen, die auf Grund kreislaufmechanischer Daten bei Lebenden errechnet werden können. Die zugleich direkt ermitteltenSpeichervolumina von Gesamtaorten erweisen sich etwa bis zum 50. Lebensjahr annähernd dem halben Herzschlagvolumen gleich. Die Gegenüberstellung derAorten-Volumendehnbarkeit verschiedener Altersstufen ergibt, daß diese im Verlauf des Lebens einer gesetzmäßigen Entwicklung unterworfen ist, in der diePhase der zunehmenden Dehnbarkeit (von der Geburt an bis zum Alter von 10–20 Jahren) und die darauffolgende Phase desfortschreitenden Dehnbarkeitsverlustes zu unterscheiden ist. — Die Aorten vonHypertonikern höherer Altersstufen (7. Lebensdekade) weisen ein wesentlichgrößeres Fassungsvermögen auf und sind zugleichetwas dehnbarer als die Aorten der Normotoniker. Die im höheren Alter oft verstärkt auftretendeherdförmige Arteriosklerose der Aorta setzt ihre Volumendehnbarkeit über den Altersdurchschnitt herab.Das stärkere Befallensein der Bauchaorta durch die herdförmigen sklerotischen Veränderungen wird vermutlich durch ihre von vornherein geringere Dehnbarkeit und einen etwas höheren altersgebundenen Dehnbarkeitsverlust mit begünstigt. Die Untersuchungder Druck-Längenbeziehungen der Aorta ergab, daß unter einem Füllungsdruck, der einer normalen intravasalen Druckbelastung entspricht,die Aorta im Körper nahezu spannungsfrei verankert ist.     

A systematic review of single-session psychological interventions ('debriefing') following trauma

BACKGROUND: Single-session psychological interventions such as psychological debriefing have become widely used following traumatic events. The evidence for their effectiveness has been widely debated. This review aimed to consider the evidence for the effectiveness of one-off early interventions within 1 month of a traumatic event. METHODS: A systematic review using the standard Cochrane Collaboration methodology. Literature searches of various databases were performed to identify randomised controlled trials. The methodological quality of the studies identified was determined using standard measures, and the results were pooled to consider the overall evidence for effectiveness. RESULTS: Eleven randomised controlled trials were found, all of individual or couple interventions. Three studies associated the intervention with a positive outcome, 6 demonstrated no difference in outcome between intervention and non-intervention groups and 2 showed some negative outcomes in the intervention group (these studies had the longest follow-up periods). The methodological quality of the studies varied widely, but was generally poor. This review suggests that early optimism for brief early psychological interventions including debriefing was misplaced and that it should not be advocated for routine use. There remains an urgent need for randomised controlled trials of group debriefing and other early interventions.     

COMP mutation screening as an aid for the clinical diagnosis and counselling of patients with a suspected diagnosis of pseudoachondroplasia or multiple epiphyseal dysplasia

The skeletal dysplasias are a clinically and genetically heterogeneous group of conditions affecting the development of the osseous skeleton and fall into the category of rare genetic diseases in which the diagnosis can be difficult for the nonexpert. Two such diseases are pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), which result in varying degrees of short stature, joint pain and stiffness and often resulting in early onset osteoarthritis. PSACH and some forms of MED result from mutations in the cartilage oligomeric matrix protein (COMP) gene and to aid the clinical diagnosis and counselling of patients with a suspected diagnosis of PSACH or MED, we developed an efficient and accurate molecular diagnostic service for the COMP gene. In a 36-month period, 100 families were screened for a mutation in COMP and we identified disease-causing mutations in 78% of PSACH families and 36% of MED families. Furthermore, in several of these families, the identification of a disease-causing mutation provided information that was immediately used to direct reproductive decision-making.     

TRIO amplification and abundant mRNA expression is associated with invasive tumor growth and rapid tumor cell proliferation in urinary bladder cancer

Studies by comparative genome hybridization have suggested that 5p amplification is related to tumor progression in urinary bladder cancer. In this study seven genes (TAS2R, ADCY2, DNAH5, CTNND2, TRIO, ANKH, and MYO10) located to 5p15.31-5p15.1 were analyzed by fluorescence in situ hybridization using a tissue microarray containing samples from tumors and cell lines with known 5p amplification by comparative genome hybridization. Amplification frequency was highest for TRIO, which maps to 5p15.2 and encodes a protein with a putative role in cell-cycle regulation. To further investigate the role of TRIO amplification in bladder cancer, a tissue microarray containing samples from 2317 bladder tumors was used for fluorescence in situ hybridization analysis. TRIO amplification was strongly associated with invasive tumor phenotype, high tumor grade, and rapid tumor cell proliferation (Ki67 LI) (P < 0.0001 each). Only 7 of 456 pTaG1/G2 tumors (1.5%) but 62 of 485 pT1-4 carcinomas (12.8%) had TRIO amplification. TRIO amplification was not associated with poor prognosis. Using a frozen bladder tumor tissue microarray RNA in situ hybridization confirmed that TRIO is up-regulated in amplified tumors. It is concluded that TRIO up-regulation through amplification has a potential role in bladder cancer progression.     

Intracellular mechanisms governing the acute phase of β-endorphin secretion from the corticotrope in vitro

It is not certain which protein kinase (A, C or both) is involved in the acute phase of β-endorphin (β-EP) release stimulated in the corticotrope by vasopressin (VP) and corticotropin-releasing factor (CRF). We have employed an isolated ovine anterior pituitary cell superfusion system to determine the dynamic effects of forskolin, a protein kinase A (PKA) stimulator, and phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator. Both secretagogues stimulated β-EP release within 5 min and therefore both PKA and PKC are potential mediators of the acute phase of hormonal stimulation of the corticotrope. Pretreatment with PMA specifically desensitized the pituitary cell columns to subsequent PMA exposure while not significantly altering sensitivity to forskolin or 50 mM KCl.