Treatment of myofascial trigger points in common shoulder disorders by physical therapy: A randomized controlled trial [ISRCTN75722066]

Background  

Shoulder disorders are a common health problem in western societies. Several treatment protocols have been developed for the clinical management of persons with shoulder pain. However available evidence does not support any protocol as being superior over others. Systematic reviews provide some evidence that certain physical therapy interventions (i.e. supervised exercises and mobilisation) are effective in particular shoulder disorders (i.e. rotator cuff disorders, mixed shoulder disorders and adhesive capsulitis), but there is an ongoing need for high quality trials of physical therapy interventions. Usually, physical therapy consists of active exercises intended to strengthen the shoulder muscles as stabilizers of the glenohumeral joint or perform mobilisations to improve restricted mobility of the glenohumeral or adjacent joints (shoulder girdle). It is generally accepted that a-traumatic shoulder problems are the result of impingement of the subacromial structures, such as the bursa or rotator cuff tendons. Myofascial trigger points (MTrPs) in shoulder muscles may also lead to a complex of symptoms that are often seen in patients diagnosed with subacromial impingement or rotator cuff tendinopathy. Little is known about the treatment of MTrPs in patients with shoulder disorders.     

CNS 7056: A Novel Ultra-short-acting Benzodiazepine

Background: A new benzodiazepine derivative, CNS 7056, has been developed to permit a superior sedative profile to current agents, i.e., more predictable fast onset, short duration of sedative action, and rapid recovery profile. This goal has been achieved by rendering the compound susceptible to metabolism via esterases. The authors now report on the profile of CNS 7056 in vitro and in vivo.

Methods: The affinity of CNS 7056 and its carboxylic acid metabolite, CNS 7054, for benzodiazepine receptors and their selectivity profiles were evaluated using radioligand binding. The activity of CNS 7056 and midazolam at subtypes ([alpha]1[beta]2[gamma]2, [alpha]2[beta]2[gamma]2, [alpha]3[beta]2[gamma]2, [alpha]5[beta]2[gamma]2) of the [gamma]-aminobutyric acid type A (GABAA) receptor was evaluated using the whole cell patch clamp technique. The activity of CNS 7056 at brain benzodiazepine receptors in vivo was measured in rats using extracellular electrophysiology in the substantia nigra pars reticulata. The sedative profile was measured in rodents using the loss of righting reflex test.

Results: CNS 7056 bound to brain benzodiazepine sites with high affinity. The carboxylic acid metabolite, CNS 7054, showed around 300 times lower affinity. CNS 7056 and CNS 7054 (10 [mu]m) showed no affinity for a range of other receptors. CNS 7056 enhanced GABA currents in cells stably transfected with subtypes of the GABAA receptor. CNS 7056, like midazolam and other classic benzodiazepines, did not show clear selectivity between subtypes of the GABAA receptor. CNS 7056 (intravenous) caused a dose-dependent inhibition of substantia nigra pars reticulata neuronal firing and recovery to baseline firing rates was reached rapidly. CNS 7056 (intravenous) induced loss of the righting reflex in rodents. The duration of loss of righting reflex was short (< 10 min) and was inhibited by pretreatment with flumazenil.     

Aztreonam for treating meningitis caused by gram-negative rods

10 patients with meningitis due to unusual gram-negative organisms (Pseudomonas, Proteus, Salmonella and Klebsiella) were effectively treated with aztreonam. A detailed history and a thorough physical examination combined with careful laboratory testing resulted in accurate diagnosis and cure of all patients.     

Dexamethasone adjunctive treatment for tuberculous meningitis

During a 5-year period, 280 of 2010 patients admitted to the meningitis ward of a referral hospital in Cairo, Egypt, were clinically diagnosed as having tuberculous meningitis and were treated with either antituberculous chemotherapy and dexamethasone or antituberculous chemotherapy alone. Fatality rates and neurologic sequelae were compared for the 2 treatment groups in the 160 patients who had cerebrospinal fluid cultures positive for Mycobacterium tuberculosis. The overall mortality rate of 51% reflects the delay in receiving appropriate therapy (79% with symptoms for more than 2 weeks) and the severity of illness on admission (56% in coma, 39% drowsy). The fatality rate was significantly lower in the group receiving dexamethasone (43% vs. 59%, P less than 0.05), particularly in the drowsy patients (15% vs. 40% P less than 0.04), and in patients surviving long enough to receive at least 10 days of treatment (14% vs. 33%, P less than 0.02). Development of neurologic complications after initiation of therapy (4 vs. 10) and permanent sequelae (6 vs. 13) were significantly lower in the dexamethasone-treated group (P less than 0.02).     

Leukaemia Inhibitory Factor or Related Factors Promote the Differentiation of Neuronal and Astrocytic Precursors within the Developing Murine Spinal Cord

Previously we have shown that leukaemia inhibitory factor (LIF) potentiates the development of murine spinal cord neurons in vitro , suggesting that it, or related factors, may play an important regulatory role in neuronal development. We have further investigated this role and show here that the generation of neurons in cultures of embryonic day 10 spinal cord cells is inhibited by antibodies to the β subunit of the LIF receptor. Since there are more undifferentiated precursors in antibody-treated cultures than in control and LIF-treated cultures, it is concluded that the primary action of LIF, or related molecules, is to promote neuronal differentiation, not precursor survival. In addition, the failure of LIF to support neuronal survival in the period immediately following differentiation suggests that the increased numbers of neurons generated with LIF are not attributable to its neurotrophic action. By selecting neuronal precursors on the basis of their inability to express class I major histocompatibility complex molecules, it was shown that LIF acted directly upon these cells and not via an intermediary cell. LIF also appears to be involved in regulating the differentiation of astrocytes, since it increases the number of glial fibrillary protein (GFAP)-positive cells present in the cultures and since the spontaneous production of GFAP-positive cells is blocked by antibodies to the LIF β receptor. These findings suggest that LIF or related factors promote the differentiation of neural precursors in the spinal cord, but that they are not involved in preferentially promoting precursors down a specific differentiation pathway.