Friedreich's Ataxia: from the (GAA)n repeat mediated silencing to new promising molecules for therapy.

Friedreich's ataxia (FRDA) is a neurodegenerative disease due to a pathological expansion of a GAA triplet repeat in the first intron of the FXN gene encoding for the mitochondrial protein frataxin. The expansion is responsible for most cases of FRDA through the formation of a nonusual B-DNA structure and heterochromatin conformation that determine a direct transcriptional silencing and the subsequent reduction in frataxin expression. Among other functions, frataxin is an iron chaperone central for the assembly of iron-sulfur clusters in mitochondria; its reduction is associated with iron accumulation in mitochondria, increased cellular sensitivity to oxidative stress and cell damage. There is, nowadays, no effective therapy for FRDA and current therapeutic strategies mainly act to slow down the consequences of frataxin deficiency. Therefore, drugs that are able to increase the amount of frataxin are excellent candidates for a rational approach to FRDA therapy. Recently, several drugs have been assessed for their ability to increase the amount of cellular frataxin, including human recombinant erythropoietin, histone deacetylase inhibitors, and the PPAR-gamma agonists.

A comparison of a refrigerant and a topical anesthetic gel as preinjection anesthetics: a clinical evaluation.

BACKGROUND: The authors used a split-mouth design to determine the effectiveness of a refrigerant compared with that of a topical anesthetic gel in reducing the pain experienced during a posterior palatal anesthetic injection. METHODS: Sixteen participants received a five-second application of a refrigerant (1,1,1,3,3-pentafluoropropane/1,1,1,2-tetrafluoroethane) and a two-minute application of a topical anesthetic gel (20 percent benzocaine gel) in the posterior palatal area before an injection of a local anesthetic solution was administered with a 30-gauge needle. Participants rated the pain they experienced after each injection by using a 100-millimeter visual analog scale (VAS) with endpoints of "no pain" and "worst possible pain." The authors calculated VAS scores by measuring the distance in millimeters from the no pain end of the scale. They analyzed data with a paired t test (alpha = .05). RESULTS: The group receiving the refrigerant had a mean VAS score of 17.7 +/- 15.3 mm, and the group receiving the topical anesthetic gel had a VAS score of 26.2 +/- 18.0 mm. The use of the refrigerant compared with the use of topical anesthetic gel significantly reduced the pain experienced during administration of local anesthetic injections (P = .02). CONCLUSIONS: The use of a refrigerant as a preinjection anesthetic was more effective compared with the use of a topical anesthetic gel in reducing the pain experienced by participants who received a posterior palatal injection. CLINICAL IMPLICATIONS: The potential benefits of using a refrigerant rather than a topical anesthetic gel are pain reduction, decreased application time, ease of application and avoidance of displeasing taste.

Topical vapocoolant quickly and effectively reduces vaccine-associated pain: results of a randomized, single-blinded, placebo-controlled study.

BACKGROUND: Comprehensive international travel preparation often requires several vaccines. Up to 90% of adults have some fear of injections, mostly due to injection-related pain. Pediatric studies with routine vaccines have shown topical anesthetic EMLA cream (lidocaine and prilocaine, Astra Pharmaceuticals, Inc.) and the topical vapocoolant Fluori-Methane (dichlorodifluoromethane and trichlorodifluoromethane, Gebauer Co.) to be equally effective in reducing pain from vaccinations. EMLA cream is expensive and requires a 60-min application, while Fluori-Methane (FM) is immediate in onset of action and inexpensive. Skin anesthesia begins at 10 degrees C. Fluori-Methane can briefly cool the skin to 0 degrees C. METHODS: We studied the effectiveness of topical vapocoolant on adult clients at our international travel clinic in a randomized, controlled trial of topical FM vs. cold (4 degrees C) saline placebo. Using a preset randomization table, participants served as their own controls, receiving placebo/control or active agent (participant blinded) in one arm (left or right), and a similar number of vaccines in the untreated arm. Vaccines were administered according to a set protocol per arm to minimize the risk of bias. Pain was measured using a modified McGill present pain intensity (PPI) pain index. Subjects rated their pain immediately and at 5 min on a six-level scale, noting treated and untreated arms separately. A questionnaire was completed on intervention preferences. Sample size was predetermined to achieve 90% statistical power estimating 25% efficacy (minimum n=172). RESULTS: One hundred and eighty-five participants were enrolled; 93 FM and 92 cold saline placebo. FM-treated arms had a significant reduction in immediate pain compared to untreated arms (pain scale mean 2.2 vs. 3.1; p<.0001), and compared to placebo (mean 2.2 vs. 2.8; p<.01). Delayed pain at 5 min was not affected by FM or control (mean 1.9 vs. 2.0) compared to no intervention (pain scale 1.9). The intervention preference questionnaire indicated that participants did not find FM therapy uncomfortable. They would choose FM therapy in the future, over a cream, especially if a wait was involved. CONCLUSION: The topical vapocoolant Fluori-Methane is an effective, quick, preferred, inexpensive agent for reducing vaccine-associated injection pain for international travel clients.

Small airway asthma therapy, challenges, and the future.

The clinical significance of small airway pathology makes these passages an important therapeutic target in asthma. Conventional chlorofluorocarbon-based formulations of inhaled corticosteroids for asthmatic inflammation produce aerosols with a relatively large particle size, and as such, offer poor access to the small airways. New corticosteroid formulations use hydrofluoroalkane propellants with a smaller average particle size, allowing better access to the distal lung. By extending the delivery of this medication to the peripheral lung and by increasing the efficiency of lung targeting, these new corticosteroid formulations provide more effective treatment at reduced drug doses.

Vapocoolant spray is equally effective as EMLA cream in reducing immunization pain in school-aged children.

BACKGROUND: Untreated immunization pain causes undue distress and contributes to underimmunization through physician, and possibly parental, resistance to multiple simultaneous injections. OBJECTIVE: To compare the efficacies of two pain management methods in reducing immediate immunization injection pain and distress in school-aged children. DESIGN: A randomized, controlled clinical trial of eutectic mixture of local anesthetics (EMLA) cream and vapocoolant spray. PATIENTS: Children aged 4 to 6 years and scheduled to receive diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) during health supervision visits. INTERVENTIONS: Enrolled children were randomized to one of three treatment groups: 1) EMLA cream + distraction; 2) vapocoolant spray + distraction; or 3) distraction alone (control). The specific pharmacologic pain control interventions consisted of EMLA cream (2.5% lidocaine, 2.5% prilocaine [Astra Pharmaceutical Products, Inc, Westborough, MA] $15. 00/patient; applied 60 minutes before injection) and vapocoolant spray (Fluori-Methane [Gebauer Company, Cleveland, OH] $0. 50/patient; applied via spray-saturated cotton ball for 15 seconds immediately before injection). MAIN OUTCOME MEASURES: The blinded investigator (BI) measured (by edited videotape) cry duration and the number of pain behaviors using the Observational Scale of Behavioral Distress. Pain visual analog scales (linear and faces scales) were completed by the child, parent, nurse, and the BI. RESULTS: Sixty-two children, aged 4.5 +/- 0.4 years (mean +/- SD) were randomized. The three treatment groups had similar subject characteristics. All pain measures and cry duration were similar for EMLA and vapocoolant spray. Both EMLA and spray were significantly better than control. Results for spray vs control: cry duration (seconds): 8.5 +/- 21.0 vs 38.6 +/- 50.5; number of pain behaviors: 1.2 +/- 1.9 vs. 3.1 +/- 2.1; child-scored faces scale: 2.0 +/- 2.4 vs. 4.1 +/- 2.3; parent-scored faces scale: 1.6 +/- 1.6 vs. 3.0 +/- 1.7; nurse-scored faces scale: 1.6 +/- 1.2 vs. 3.1 +/- 1.4; and BI-scored faces scale: 1.0 +/- 1.5 vs. 2.4 +/- 1.4. CONCLUSIONS: When combined with distraction, vapocoolant spray significantly reduces immediate injection pain compared with distraction alone, and is equally effective as, less expensive, and faster-acting than EMLA cream. As an effective, inexpensive, and convenient pain control method, vapocoolant spray may help overcome physician and parent resistance to multiple injections that leads to missed opportunities to immunize.

Clinical care for myofascial pain.

Myofascial pain (MFP) is a regional muscle pain disorder characterized by localized tenderness in taut muscle bands and referred pain. Frequently, MFP is overlooked as a common cause of chronic pain because of the frequent association with joint dysfunction and other pain disorders and the multiple behavioral and psychosocial contributing factors that are often present. Nonetheless, studies have reported that MFP is present in a significant number of people. This article describes current concepts for the diagnosis and management of MFP.

Quantification of changes in myofascial trigger point sensitivity with the pressure algometer following passive stretch.

In order to determine the relationship between trigger point sensitivity and the referred symptoms of myofascial pain, VAS ratings of referred pain intensity and pressure algometer measures of myofascial trigger point sensitivity were taken pre and post treatment of the muscle containing the trigger point with passive stretch. The results in 20 subjects, experiencing unilateral or bilateral myofascial head and neck pain, showed that myofascial trigger point sensitivity decreases in response to passive stretch as assessed by the pressure algometer, and that trigger point sensitivity and intensity of referred pain are related.

The treatment of soft tissue after spinal injury.

There are a number of modalities available for the treatment of soft tissue that are applicable to spinal injuries. Each has a long history of use; however, there is relatively little scientific data to support the effects often seen in the clinical setting. Only through careful evaluation and specific diagnosis can these methods of treatment be utilized to their fullest potential. The underlying pathology must always be addressed as well as its soft-tissue manifestations. Direct treatment of the mechanical derangement must take precedence when such conditions exist. The total treatment must incorporate patient education in posture and positioning as well as prophylactic measures. In later stages of rehabilitation, a general strengthening program to further prevent reinjury should be embarked upon. It must always be remembered that treatment of soft tissue alone rarely provides long-lasting relief of symptoms.

Myofascial trigger points in persistent posttraumatic shoulder pain.

Persistent pain and disability after injuries to the shoulder sometimes create a difficult diagnostic and therapeutic problem. In many such cases, myofascial trigger points seem to cause symptoms. Three cases in which pain had persisted for eight to 33 months after injury illustrate the manifestations of posttraumatic myofascial trigger point disorders. Trigger points are located by finding discrete foci of tenderness in muscles. Trigger points may be palpably firmer than surrounding muscle, forming nodules; they may twitch in response to palpation and may refer pain to a specific area when stimulated. Failure to recognize the myofascial source of pain can lead to erroneous diagnoses of articular, neurologic, or emotional disorder. Current pathophysiologic theories about trigger points may explain the persistence and topographic spreading of pain after muscular injuries. Appropriate treatment of myofascial trigger points can relieve chronic pain and disability.

Myofascial origins of low back pain. 1. Principles of diagnosis and treatment.

Myofascial trigger points (TPs) are frequently overlooked sources of acute and chronic low back pain. An active myofascial TP is suspected by its focal tenderness to palpation and by restricted stretch range of motion. The restricted lengthening of the muscle is due to the tense band of muscle fibers in which the TP is located. The presence of a TP is confirmed by a local twitch response and by reproduction of its known pattern of referred pain, which matches the distribution of the patient's pain. Only an active TP causes a clinical pain complaint; a latent TP does not. The pain can be relieved by the stretch-and-spray procedure, ischemic compression, or precise injection of the TP with procaine solution. Relief is usually long lasting only if mechanical and systemic perpetuating factors are corrected.

Effect of Fluori-Methane spray on passive hip flexion.

The purpose of the study was to evaluate the influence of Fluori-Methane spray as a method of affecting passive range of motion measured at the right hip joint. Subjects were 30 normal volunteers randomly divided into an experimental group and a control group. A special table was constructed to position and stabilize each subject for monitoring the right lower extremity's resistance to side-lying straight leg raising. Specific right hip flexion goniometric measurements were compared and analyzed before and after application of Fluori-Methane spray to the soft tissue overlying the posterior part of the right thigh. The results of the study showed that the experimental group, which received application of Fluori-Methane spray and static passive stretch, did significantly (p less than .02) increase the range of passive hip flexion over that of the control group, which received only static passive stretch.

Pneumatic power supply for intravenous infusions.

The pneumatic power supply (PPS) has been used as the driving device for the pneumatic blood pump during the resuscitation of more than 15 hypovolemic patients. The device has been found to be safe and easy to use. By virtue of its semiautomatic function, members of the resuscitation team are free to perform other duties. Previously, these individuals would have been required to maintain an adequate driving pressure in the infusion pumps.