Developmental constraint of insect audition

Background

Insect ears contain very different numbers of sensory cells, from only one sensory cell in some moths to thousands of sensory cells, e.g. in cicadas. These differences still await functional explanation and especially the large numbers in cicadas remain puzzling. Insects of the different orders have distinct developmental sequences for the generation of auditory organs. These sensory cells might have different functions depending on the developmental stages. Here we propose that constraints arising during development are also important for the design of insect ears and might influence cell numbers of the adults.

Presentation of the hypothesis

We propose that the functional requirements of the subadult stages determine the adult complement of sensory units in the auditory system of cicadas. The hypothetical larval sensory organ should function as a vibration receiver, representing a functional caenogenesis.

Testing the hypothesis

Experiments at different levels have to be designed to test the hypothesis. Firstly, the neuroanatomy of the larval sense organ should be analyzed to detail. Secondly, the function should be unraveled neurophysiologically and behaviorally. Thirdly, the persistence of the sensory cells and the rebuilding of the sensory organ to the adult should be investigated.

Implications of the hypothesis

Usually, the evolution of insect ears is viewed with respect to physiological and neuronal mechanisms of sound perception. This view should be extended to the development of sense organs. Functional requirements during postembryonic development may act as constraints for the evolution of adult organs, as exemplified with the auditory system of cicadas.     

Detection of coronary microembolization by Doppler ultrasound in patients with stable angina pectoris during percutaneous coronary interventions under an adjunctive antithrombotic therapy with abciximab: design and rationale of the High Intensity Transient Signals ReoPro (HITS-RP) study

Background

Embolization of atherosclerotic debris from the rupture of a vulnerable atherosclerotic plaque occurs iatrogenically during percutaneous coronary interventions (PCI) and can induce myocardial necrosis. These microembolizations are detected as high intensity transient signals (HITS) using intracoronary Doppler technology.

Presentation of the hypothesis

In the presented study we will test if abciximab (ReoPro?) infusion reduces high intensity transient signals in patients with stable angina pectoris undergoing PCI in comparison to standard therapy alone.

Testing the hypothesis

The High Intensity Transient Signals ReoPro? (HITS-RP) study will enroll 60 patients. It is a prospective, single center, randomized, double-blinded, controlled trial. The study is designed to compare the efficacy of intravenous abciximab administration for reduction of microembolization during elective PCI. Patients will be randomized in a 1:1 fashion to abciximab or placebo infusion. The primary end point of the HITS-RP-Study is the number of HITS during PCI measured by intracoronary Doppler wire. Secondary endpoints are bleeding complications, elevation of cardiac biomarkers or ECG changes after percutaneous coronary interventions, changes in coronary flow velocity reserve, hs-CRP elevation, any major adverse cardio-vascular event during one month follow-up.

Implications of the hypothesis

The HITS-RP-Study addresses important questions regarding the efficacy of intravenous abciximab administration in reducing microembolization and periprocedural complications in stable angina pectoris patients undergoing PCI.

Trial registration

The trial is registered under http://www.drks-neu.uniklinik-freiburg.de/drks_web/:DRKS00000603.     

Apoptosis and signalling in acid sphingomyelinase deficient cells

Background

Recent evidence suggests that the activation of a non-specific lipid scramblase during apoptosis induces the flipping of sphingomyelin from the cell surface to the cytoplasmic leaftet of the plasma membrane. Inner leaflet sphingomyelin is then cleaved to ceramide by a neutral sphingomyelinase. The production of this non-membrane forming lipid induces blebbing of the plasma membrane to aid rapid engulfment by professional phagocytes. However contrary evidence suggests that cells which are deficient in acid sphingomyelinase are defective in apoptosis signalling. This data has been interpreted as support for the activation of acid sphingomyelinase as an early signal in apoptosis.

Hypothesis

An alternative explanation is put forward whereby the accumulation of intracellular sphingomyelin in sphingomyelinase deficient cells leads to the formation of intracellular rafts which lead to the sequestration of important signalling molecules that are normally present on the cell surface where they perform their function.

Testing the hypothesis

It is expected that the subcellular distribution of important signalling molecules is altered in acid sphingomyelinase deficient cells, leading to their sequestration in late endosomes / lysosomes. Other sphingolipid storage diseases such as Niemann-Pick type C which have normal acid sphingomyelinase activity would also be expected to show the same phenotype.

Implications of the hypothesis

If true the hypothesis would provide a mechanism for the pathology of the sphingolipid storage diseases at the cellular level and also have implications for the role of ceramide in apoptosis.     

Beta blocker use in subjects with type 2 diabetes mellitus and systolic heart failure does not worsen glycaemic control

Background

The decrease and dysfunction of endothelial progenitor cells (EPCs) has been assumed as an important cause/consequence of diabetes mellitus (DM) and its complications, in which the senescence of EPCs induced by hyperglycemia may play an immensurable role. However, the mechanisms of EPCs senescence has not been fully investigated. Recently, ribosomal protein S6 kinase 4 (RSK4), a member of serine/threomine (Ser/Thr) kinase family and p53-related gene, is reported to regulate the replicative and stress-induced senescence of different cells.

Presentation of the hypothesis

These above lead to consideration of an evidence-based hypothesis that RSK4 may serve as a mediator of EPCs senescence in DM.

Testing the hypothesis

EPCs of healthy subjects and DM patients are isolated from peripheral blood and incubated with high glucose (HG). Then, the EPCs senescence would be detected by senescence associated ??-galactosides (SA-??-gal) staining. Meanwhile, the RSK4 expression is assessed by RT-PCR and western blot. Moreover, overexpressing or RNA interfering of RSK4 in EPCs to investigate the relationship between RSK4 expression and the senescence of EPCs are necessary to substantiate this hypothesis. Also, studies on possible upstream and downstream factors of RSK4 would be explored to reveal the RSK4-mediated senescence pathway in EPCs.

Implications of the hypothesis

If proved, this hypothesis will provide another mediator of EPCs senescence, and may establish a novel pathogenesis for DM and further benefit to the management of DM.     

La fibromyalgie est-elle une maladie psychiatrique ?

Epidemiology

The lifetime prevalence of fibromyalgia in France is estimated between 1.4% and 2.2%. The male/female sex ratio is 1:7, and symptoms usually appear between the age of30 and 50 years.

Diagnosis

The diagnosis of fibromyalgia is now a rheumatologic diagnosis, based on symptoms including chronic widespread pain and nonrestorative sleep. As fibromyalgia is a highly comorbid disease, it questions about nosographic identity.

Diagnosing psychiatric comorbidity

It is important for the clinician to look for symptoms of depression that are not traditionally comorbid with fibromyalgia: suicidal ideation, anhedonia, self-blame, eating disorders and psychomotor retardation. An anxiety disorder is often secondary to the onset of symptoms, and can sometimes precede the onset of fibromyalgia syndrome. The vast majority of patients with fibromyalgia have a history of traumatic life events.

Pharmacological treatments

The medical treatment to the fibromyalgia syndrome is not necessarily a drug. Treatment of fibromyalgia is currently not the subject to marketing authorization in France and Europe. Pregabalin, duloxetine and milnacipran received marketing authorization for treatment of fibromyalgia in the US, but none have proven effective in the long term. Fibromyalgia, therefore, requires multidisciplinary support from rheumatologists (who make the diagnosis), general practitioners (who guide and advise patients), medical pain specialists and psychiatrists for the treatment of comorbidities.     

Non-systemic metamorphosis in male millipede appendages: long delayed, reversible effect of an early localized positional marker?

Background

The development of specialized appendages involved in sperm transfer in the males of julid millipedes is an extreme case of specialized, complex structures differentiating in a very advanced phase of post-embryonic development. Here, a non-systemic metamorphosis affects the external morphology and the internal anatomy of a trunk double segment only.

Presentation of the hypothesis

We hypothesize that during early (possibly embryonic) development a segmental marker is produced that remains unexploited throughout late embryonic and early post-embryonic development, until, activated by a systemic signal, it finally determines the release of a segmentally localized but anatomically major change.

Testing the hypothesis

Key to testing the hypothesis are (1) the identification of both the putative segmental marker involved in the localization of the legs to be eventually metamorphosed into gonopods and the systemic signal activating it, (2) the identification of the cell population from which the gonopods are built, and (3) a longitudinal study of the marker's expression throughout late embryonic and, possibly, post-embryonic development.

Implications of the hypothesis

Proving the validity of this hypothesis would demonstrate the existence of a cryptic developmental module that will be activated only months, or years, after it has been first laid down during early development. This study also opens a window onto the very poorly explored domain of late expression of developmental genes and molecular control of late developmental events.     

Pharmacokinetics of recombinant human growth hormone administered by cool.click™ 2, a new needle-free device,compared with subcutaneous administration using a conventional syringe and needle

Background

Growth hormone (GH) is used to treat growth hormone deficiency (GHD, adult and paediatric), short bowel syndrome in patients on a specialized diet, HIV-associated wasting and, in children, growth failure due to a number of disorders including Turner's syndrome and chronic renal failure, and in children born small for gestational age. Different brands and generic forms of recombinant human growth hormone (r-hGH) are approved for varying indications in different countries. New ways of administering GH are required because the use of a needle and syringe or a device where a patient still has to insert the needle manually into the skin on a daily basis can lead to low adherence and sub-optimal treatment outcomes. The objective of this study was to assess the relative bioavailability of r-hGH (Saizen^®, Merck Serono) administered by a new needle-free device, cool.click? 2, and a standard needle and syringe.

Methods

The study was performed with 38 healthy volunteers who underwent pituitary somatotrope cell down-regulation using somatostatin, according to a randomized, two-period, two-sequence crossover design. Following subcutaneous administration of r-hGH using cool.click? 2 or needle and syringe, pharmacokinetic parameters were analysed by non-compartmental methods. Bioequivalence was assessed based on log-transformed AUC and C_max values.

Results

The 90% confidence intervals for test/reference mean ratio of the plasma pharmacokinetic variables C_max and AUC_0-inf were 103.7–118.3 and 97.1–110.0, respectively, which is within the accepted bioequivalence range of 80–125%. r-hGH administered by cool.click? 2 is, therefore, bioequivalent to administration by needle and syringe with respect to the rate and extent of GH exposure. Treatment using cool.click? 2 was found to be well tolerated. With cool.click? 2 the t_max was less (3.0 hours) than for needle and syringe delivery (4.5 hours), p = 0.002 (Friedman test), although this is unlikely to have any clinical implications.

Conclusion

These results demonstrate that cool.click? 2 delivers subcutaneous r-hGH exposure that is bioequivalent to the conventional mode of injection. The new device has the additional advantage of being needle-free, and should help to increase patient adherence and achieve good therapeutic outcomes from r-hGH treatment.

     

Osteopathic manipulative treatment and its relationship to autonomic nervous system activity as demonstrated by heart rate variability: a repeated measures study

Background

Osteopathic manipulative treatment (OMT) and ultrasound physical therapy (UPT) are commonly used for chronic low back pain. Although there is evidence from a systematic review and meta-analysis that OMT generally reduces low back pain, there are no large clinical trials that specifically assess OMT efficacy in chronic low back pain. Similarly, there is a lack of evidence involving UPT for chronic low back pain.

Methods

The OSTEOPAThic Health outcomes In Chronic low back pain (OSTEOPATHIC) Trial is a Phase III randomized controlled trial that seeks to study 488 subjects between August 2006 and June 2010. It uses a 2 × 2 factorial design to independently assess the efficacy of OMT and UPT for chronic low back pain. The primary outcome is a visual analogue scale score for pain. Secondary outcomes include back-specific functioning, generic health, work disability, and satisfaction with back care.

Conclusion

This randomized controlled trial will potentially be the largest involving OMT. It will provide long awaited data on the efficacy of OMT and UPT for chronic low back pain.

Trial registration

http://www.clinicaltrials.gov, NCT00315120     

Low-volume jet injection for intradermal immunization in rabbits

Background

This study tested a low-volume (20–30 μl/20–30 μg DNA) jet injection method for intradermal delivery of a DNA vaccine. Jet injection offers the advantages of a needle-less system, low-cost, rapid preparation of the injected DNA solution, and a simple delivery system. More than one construct can be injected simultaneously and the method may be combined with adjuvants.

Results

Low-volume jet injection targeted delivery of a DNA solution exclusively to the dermis and epidermis of rabbits. A three injection series of plasmid DNA, encoding the Hepatitis B Surface Antigen stimulated a humoral immune response in 2/5 rabbits. One rabbit developed a significant rise in antibody titer after 1 injection and one following 2 injections. There were no significant differences between jet injection and particle bombardment in the maximal antibody titers or number of injections before response. A three injection series of the same plasmid DNA by particle bombardment elicited a significant rise in antibody titer in 3/5 rabbits. One rabbit developed antibody after 1 injection and two after 3 injections. In contrast, 0/5 rabbits receiving DNA by needle and syringe injection responded. In the jet injection and particle bombardment groups, gene expression levels in the skin did not predict response. While immune responses were similar, luciferase gene expression levels in the skin following particle bombardment were 10–100 times higher than jet injection.

Conclusion

Low-volume jet injection is a simple, effective methodology for intradermal DNA immunization.     

Spatiotemporal dynamics of re-innervation and hyperinnervation patterns by uninjured CGRP fibers in the rat foot sole epidermis after nerve injury

Background

Minocycline prevents the development of neuropathic and inflammatory pain by inhibiting microglial activation and postsynaptic currents. But, how minocycline obviates acute visceral pain is unclear. The present study investigated whether minocycline had an any antinociceptive effect on acetic acid-induced acute abdominal pain after intraperitoneal (i.p.) administration of saline or minocycline 1 hour before acetic acid injection (1.0%, 250 ??l, i.p.).

Results

Minocycline (4, 10, or 40 mg/kg) significantly decreased acetic acid-induced nociception (0-60 minutes post-injection) and the enhancement in the number of c-Fos positive cells in the T5-L2 spinal cord induced by acetic acid injection. Also, the expression of spinal phosphorylated extracellular signal-regulated kinase (p-ERK) induced by acetic acid was reduced by minocycline pre-administration. Interestingly, intrathecal introduction of PD98059, an ERK upstream kinase inhibitor, markedly blocked the acetic acid-stimulated pain responses.

Conclusions

These results demonstrate that minocycline effectively inhibits acetic acid-induced acute abdominal nociception via the inhibition of neuronal p-ERK expression in the spinal cord, and that minocycline may have therapeutic potential in suppressing acute abdominal pain.     

A randomized, controlled trial of spinal endoscopic adhesiolysis in chronic refractory low back and lower extremity pain [ISRCTN 16558617]

Background

Postoperative epidural fibrosis may contribute to between 5% to 60% of the poor surgical outcomes following decompressive surgery. Correlations have been reported between epidural scarring and radicular pain, poor surgical outcomes, and a lack of any form of surgical treatment. The use of spinal endoscopic adhesiolysis in recent years in the management of chronic refractory low back and lower extremity pain has been described.

Methods

A prospective, randomized, double-blind trial was conducted to determine the outcome of spinal endoscopic adhesiolysis to reduce pain and improve function and psychological status in patients with chronic refractory low back and lower extremity pain. A total of 83 patients were evaluated, with 33 patients in Group I and 50 patients in Group II. Group I served as the control, with endoscopy into the sacral level without adhesiolysis, followed by injection of local anesthetic and steroid. Group II received spinal endoscopic adhesiolysis, followed by injection of local anesthetic and steroid.

Results

Among the 50 patients in the treatment group receiving spinal endoscopic adhesiolysis, significant improvement without adverse effects was shown in 80% at 3 months, 56% at 6 months, and 48% at 12 months. The control group showed improvement in 33% of the patients at one month and none thereafter. Based on the definition that less than 6 months of relief is considered short-term and longer than 6 months of relief is considered long-term, a significant number of patients obtained long-term relief with improvement in pain, functional status, and psychological status.

Conclusion

Spinal endoscopic adhesiolysis with targeted delivery of local anesthetic and steroid is an effective treatment in a significant number of patients with chronic low back and lower extremity pain without major adverse effects.     

Moderate ischemic mitral regurgitation (IMR) and metabolic syndrome: where are we now and where are we going?

Background

The metabolic syndrome appears to affect 10% to 25% of adult population worldwide. Several studies have described the association between metabolic syndrome and ischaemic heart disease, however, none linked metabolic syndrome to ischemic mitral regurgitation, a serious clinical problem facing both the cardiologists and cardiac surgeons. Ischemic mitral regurgitation is mitral insufficiency caused by myocardial infarction. The myocardial ischemia can result in altered ventricular geometry, leading to mitral insufficiency. Interestingly metabolic syndrome showed more pronounced alteration of left ventricular geometry and function especially in obese subjects.

Presentation of the hypothesis

We have recently proposed that there is link between metabolic syndrome and ischemic mitral regurgitation and associated complications. Operative strategy for moderate ischaemic mitral regurgitation continues to be debated between revascularisation alone and concomitant valve repair at the time of coronary artery bypass surgery. Each of the above group has published studies, with results supporting each argument.

Testing the hypothesis

Generally speaking the treatments available for metabolic syndrome are based in both life style modification (dietary advice and advice to increase physical activity) and medical treatment to enhance insulin sensitivity. Randomised controlled trials may show whether the current available treatment of metabolic syndrome may have an impact on moderate ischemic mitral regurgitation.

Implications of the hypothesis

Metabolic syndrome was shown to alter left ventricular geometry and therefore it is possible to postulate that the variation in the response of different patients with moderate ischemic mitral regurgitation to current management may be attributed to the absence and presence of metabolic syndrome. Research testing of this hypothesis in the future may reveal whether concomitant treatment of metabolic syndrome will play part in the management of moderate ischemic mitral regurgitation.     

Erecteur a dépression (Vacuum erection device): Mise au point

The vacuum erection device (VED) is a nonsurgical alternative for the treatment of erectile dysfunction. This method is based on 2 phenomena:

1. an erection-like state occurs when the penis is placed in a vacuum
2. this state can be maintained by a constricting band placed around the base of the penis

The erection-like state thus obtained differs from a normal erection in the following ways:

1. blood flow into the penis decreases
2. penile skin temperature falls
3. congestion of extra-corporeal penile tissues occurs
4. the penis pivots at its base
5. the ejaculate is trapped in the proximal urethra

About 30 to 60% of men who trie the device at home purchase it for continued use. The others are unable to achieve sufficient rigidity, experience side-effects or dislike the use of the device despite good result. About 60 to 80% of the men who purchased the device continue to use it regulary at short or middle term. The VED seems to have lesser drop-out rate than the self injection therapy. The most frequently encountered side-effects of the device are pain, petechiaes, bruising and ecchymosis.     

Amiloride derivatives enhance insulin release in pancreatic islets from diabetic mice

Background

The global pattern of varying prevalence of diseases of affluence, such as obesity, cardiovascular disease and diabetes, suggests that some environmental factor specific to agrarian societies could initiate these diseases.

Presentation of the hypothesis

We propose that a cereal-based diet could be such an environmental factor. Through previous studies in archaeology and molecular evolution we conclude that humans and the human leptin system are not specifically adapted to a cereal-based diet, and that leptin resistance associated with diseases of affluence could be a sign of insufficient adaptation to such a diet. We further propose lectins as a cereal constituent with sufficient properties to cause leptin resistance, either through effects on metabolism central to the proper functions of the leptin system, and/or directly through binding to human leptin or human leptin receptor, thereby affecting the function.

Testing the hypothesis

Dietary interventions should compare effects of agrarian and non-agrarian diets on incidence of diseases of affluence, related risk factors and leptin resistance. A non-significant (p = 0.10) increase of cardiovascular mortality was noted in patients advised to eat more whole-grain cereals. Our lab conducted a study on 24 domestic pigs in which a cereal-free hunter-gatherer diet promoted significantly higher insulin sensitivity, lower diastolic blood pressure and lower C-reactive protein as compared to a cereal-based swine feed. Testing should also evaluate the effects of grass lectins on the leptin system in vivo by diet interventions, and in vitro in various leptin and leptin receptor models. Our group currently conducts such studies.

Implications of the hypothesis

If an agrarian diet initiates diseases of affluence it should be possible to identify the responsible constituents and modify or remove them so as to make an agrarian diet healthier.     

Hepatitis B and C in dialysis units in Kosova

Background

The complement system is one of the most potent weapons of innate immunity. It is not only a mechanism for direct protection against invading pathogens but it also interacts with the adaptive immunity to optimize the pathogen-specific humoral and cellular defense cascades in the body. Complement-mediated lysis of HIV is inefficient but the presence of HIV particles results in complement activation by the generation of many C3-fragments, such as C3dg and C3d. It has been demonstrated that activation of complement can enhance HIV infection through the binding of special complement receptor type 2 expression on the surface of mature B cells and follicular dendritic cells.

Presentation of the hypothesis

Previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that a new activator of complement, consisting of a target domain (C3-binding region of complement receptor type 2) linked to a complement-activating human IgG1 Fc domain (CR2-Fc), can target and amplify complement deposition on HIV virions and enhance the efficiency of HIV lysis.

Testing the hypothesis

Our hypothesis was tested using cell-free HIV-1 virions cultivatedin vitro and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified CR2-Fc proteins. As a control group, viruses were incubated with normal human serum under the same conditions. Virus neutralization assays were used to estimate the degree of CR2-Fc-enhanced lysis of HIV compared to untreated virus.

Implications of the hypothesis

The targeted complement activator, CR2-Fc, can be used as a novel approach to HIV therapy by abrogating the complement-enhanced HIV infection of cells.     

Probable presence of an ubiquitous cryptic mitochondrial gene on the antisense strand of the cytochrome oxidase I gene

Background

Mitochondria mediate most of the energy production that occurs in the majority of eukaryotic organisms. These subcellular organelles contain a genome that differs from the nuclear genome and is referred to as mitochondrial DNA (mtDNA). Despite a disparity in gene content, all mtDNAs encode at least two components of the mitochondrial electron transport chain, including cytochrome c oxidase I (Cox1).

Presentation of the hypothesis

A positionally conserved ORF has been found on the complementary strand of the cox1 genes of both eukaryotic mitochondria (protist, plant, fungal and animal) and alpha-proteobacteria. This putative gene has been named gau for gene antisense ubiquitous in mtDNAs. The length of the deduced protein is approximately 100 amino acids. In vertebrates, several stop codons have been found in the mt gau region, and potentially functional gau regions have been found in nuclear genomes. However, a recent bioinformatics study showed that several hypothetical overlapping mt genes could be predicted, including gau; this involves the possible import of the cytosolic AGR tRNA into the mitochondria and/or the expression of mt antisense tRNAs with anticodons recognizing AGR codons according to an alternative genetic code that is induced by the presence of suppressor tRNAs. Despite an evolutionary distance of at least 1.5 to 2.0 billion years, the deduced Gau proteins share some conserved amino acid signatures and structure, which suggests a possible conserved function. Moreover, BLAST analysis identified rare, sense-oriented ESTs with poly(A) tails that include the entire gau region. Immunohistochemical analyses using an anti-Gau monoclonal antibody revealed strict co-localization of Gau proteins and a mitochondrial marker.

Testing the hypothesis

This hypothesis could be tested by purifying the gau gene product and determining its sequence. Cell biological experiments are needed to determine the physiological role of this protein.

Implications of the hypothesis

Studies of the gau ORF will shed light on the origin of novel genes and their functions in organelles and could also have medical implications for human diseases that are caused by mitochondrial dysfunction. Moreover, this strengthens evidence for mitochondrial genes coded according to an overlapping genetic code.     

An MRI study on the relations between muscle atrophy, shoulder function and glenohumeral deformity in shoulders of children with obstetric brachial plexus injury

Objective

it has been established that chronic neck pain following whiplash is associated with the phenomenon of central sensitization, in which injured and uninjured parts of the body exhibit lowered pain thresholds due to an alteration in central pain processing. it has furthermore been hypothesized that peripheral sources of nociception in the muscles may perpetuate central sensitization in chronic whiplash. the hypothesis explored in the present study was whether myofascial trigger points serve as a modulator of central sensitization in subjects with chronic neck pain.

Design

controlled case series.

Setting

outpatient chronic pain clinic.

Subjects

seventeen patients with chronic and intractable neck pain and 10 healthy controls without complaints of neck pain.

Intervention

symptomatic subjects received anesthetic infiltration of myofascial trigger points in the upper trapezius muscles and controls received the anesthetic in the thigh. Outcome measures: pre and post injection cervical range of motion, pressure pain thresholds (ppt) over the infraspinatus, wrist extensor, and tibialis anterior muscles. sensitivity to light (photophobia) and subjects' perception of pain using a visual analog scale (vas) were also evaluated before and after injections. only the ppt was evaluated in the asymptomatic controls.

Results

immediate (within 1 minute) alterations in cervical range of motion and pressure pain thresholds were observed following an average of 3.8 injections with 1–2 cc of 1% lidocaine into carefully identified trigger points. cervical range of motion increased by an average of 49% (p = 0.000) in flexion and 44% (p = 0.001) in extension, 47% (p = 0.000) and 28% (p < 0.016) in right and left lateral flexion, and a 27% (p = 0.002) and 45% (p = 0.000) in right and left rotation. ppt were found increased by 68% over the infraspinatus (p = 0.000), by 78% over the wrist extensors (p = 0.000), and by 64% over the tibialis anterior (p = 0.002). among 11 subjects with photophobia, only 2 remained sensitive to light after the trigger point injections (p = 0.033). average vas dropped by 57%, from 6.1 to 2.6 (p = 0.000). no significant changes in ppt were observed in the control group following lidocaine infiltration of the thigh.

Conclusion

the present data suggest that myofascial trigger points serve to perpetuate lowered pain thresholds in uninjured tissues. additionally, it appears that lowered pain thresholds associated with central sensitization can be immediately reversed, even when associated with long standing chronic neck pain. although the effects resulting from anesthesia of trigger points in the present study were temporary, it is possible that surgical excision or ablation of the same trigger points may offer more permanent solutions for chronic neck pain patients. further study is needed to evaluate these and other options for such patients.     

Traumeel S® for pain relief following hallux valgus surgery: a randomized controlled trial

Background

In spite of recent advances in post-operative pain relief, pain following orthopedic surgery remains an ongoing challenge for clinicians. We examined whether a well known and frequently prescribed homeopathic preparation could mitigate post-operative pain.

Method

We performed a randomized, double blind, placebo-controlled trial to evaluate the efficacy of the homeopathic preparation Traumeel S^® in minimizing post-operative pain and analgesic consumption following surgical correction of hallux valgus. Eighty consecutive patients were randomized to receive either Traumeel tablets or an indistinguishable placebo, and took primary and rescue oral analgesics as needed. Maximum numerical pain scores at rest and consumption of oral analgesics were recorded on day of surgery and for 13 days following surgery.

Results

Traumeel was not found superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial, however a transient reduction in the daily maximum post-operative pain score favoring the Traumeel arm was observed on the day of surgery, a finding supported by a treatment-time interaction test (p = 0.04).

Conclusions

Traumeel was not superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial. A transient reduction in the daily maximum post-operative pain score on the day of surgery is of questionable clinical importance.

Trial Registration

This study was registered at ClinicalTrials.gov. # NCT00279513     

Delayed β-cell response and glucose intolerance in young women with Turner syndrome

Background

Accurately monitoring adherence to treatment with recombinant human growth hormone (r-hGH) enables appropriate intervention in cases of poor adherence. The electronic r-hGH auto-injector, easypod?, automatically records the patient's adherence to treatment. This study evaluated adherence to treatment of children who started using the auto-injector and assessed opinions about the device.

Methods

A multicentre, multinational, observational 3-month survey in which children received r-hGH as part of their normal care. Physicians reviewed the recorded dose history and children (with or without parental assistance) completed a questionnaire-based survey. Children missing ≤2 injections per month (92% of injections given) were considered adherent to treatment. Adherence was compared between GH treatment-naïve and treatment-experienced children.

Results

Of 834 recruited participants, 824 were evaluated. The median (range) age was 11 (1-18) years. From the recorded dose history, 87.5% of children were adherent to treatment over the 3-month period. Recorded adherence was higher in treatment-naïve (89.7%, n = 445/496) than in treatment-experienced children (81.7%, n = 152/186) [Fisher's exact test FI(X) = 7.577; p = 0.0062]. According to self-reported data, 90.2% (607/673) of children were adherent over 3 months; 51.5% (421/817) missed ≥1 injection over this period (mainly due to forgetfulness). Concordance between reported and recorded adherence was 84.3%, with a trend towards self-reported adherence being higher than recorded adherence. Most children liked the auto-injector: over 80% gave the top two responses from five options for ease of use (720/779), speed (684/805) and comfort (716/804). Although 38.5% (300/780) of children reported pain on injection, over half of children (210/363) considered the pain to be less or much less than expected. Given the choice, 91.8% (732/797) of children/parents would continue using the device.

Conclusions

easypod? provides an accurate method of monitoring adherence to treatment with r-hGH. In children who received treatment with r-hGH using easypod?, short-term adherence is good, and significantly higher in treatment-naïve children compared with experienced children. Children/parents rate the device highly. The high level of acceptability of the device is reflected by a desire to continue using it by over 90% of the children in the survey.