Morphological features of allogenic nerve segment in rats after subcutaneous embedment

IN T R O D U C T IO N Atpresent,therapy ofperipheralnerve injury is m ainly to sim ulate the regenerated physiopathologic process after injury through various m ethods. End-to-end anastom oses is adopted to elim inate tension; Autologous nerve transplanta…     

Cubital tunnel syndrome--simple nerve decompression or decompression with subcutaneous anterior transposition?

The purpose of this prospective, randomised and controlled study was to evaluate which kind of operative technique for treatment of cubital tunnel syndrome is favourable: subcutaneous anterior transposition or nerve decompression without transposition. This study included 66 patients suffering from pain and/either neurological deficits with clinically and electrographically proven cubital tunnel syndrome. 32 patients underwent nerve decompression without transposition, whereas 34 underwent subcutaneous transposition of the nerve. Follow-up examinations evaluating pain, motor and sensory deficits as well as motor nerve conduction velocities were performed three, nine and 24 months postoperatively. Irrespectively of operative procedures (simple decompression vs. subcutaneous anterior transposition) there were no significant differences between the outcomes of the two groups at either postoperative follow-up examination (p > 0.05).     

Effects of subcutaneous implant of peripheral nerve allograft on the regeneration of defected sciatic nerve

IN T R O D U C T IO NPeripheralnerve regeneration m ainly depends on m icroenvironem nt, w hich is com posed ofS chw ann cells and extracellularm atrix.M ostof extracellular m atrix is synthesized and released by S chw ann cells [1]. Therefore, the determ…     

Continuous subcutaneous apomorphine infusion in advanced Parkinson’s disease: 10-year experience with 230 patients

Continuous apomorphine infusion (APO) is one of the treatments available for advanced Parkinson disease (PD). Over 10 years, we have treated 230 patients with APO. Mean age was 66.8 and average evolution time at APO onset was 13.0 years. Mean duration of the treatment was 26.3 months. As of June 2016, 93 remained on the medication (active group), while 137 had stopped. This active group had mean age 67.3 at recruitment and mean evolution 14.2 years. The main indication for APO was lack of deep brain stimulation criteria (DBS). Twelve patients were on waiting list for DBS. Average time since APO onset was 40.0 months. In the active group, APO decreased off-state in 4 h and allowed reducing levodopa and dopamine agonists. Dyskinesia and balance did not worsen. Cognitive decline did not change within the first 15 months. Hallucinations were the same within the first 39 months. The presence of subcutaneous nodules was the most frequent adverse event in this group. The main reason for discontinuation was side effects, being psychosis the most common. Within the first year, 82 patients stopped APO. Eighteen of these patients eventually got DBS. APO is a good option for advanced PD, since it permits a significant reduction in off-time and other antiparkinsonian drugs. This effect is sustained over time. We have treated 132 patients for over a year. Dyskinesia seems not to worsen. Combining APO with DBS simultaneously or alternatively provides good results.     

Health-related quality of life in patients with relapsing-remitting multiple sclerosis treated with subcutaneous interferon β-1a in Iran

Purpose: Multiple sclerosis (MS) requires long-term therapy and can affect many aspects of a patient's life, including quality of life. MS patients score lower on health-related quality of life (HRQoL) measures. The efficacy of subcutaneous interferon (IFN) β-1a has been extensively evaluated by using objective measures but its impact on HRQoL is currently unclear. In this observational study, we evaluated HRQoL of Iranian patients with relapsing-remitting MS (RRMS) treated with IFN β-1a by using short-form 36 (SF-36) and multiple sclerosis international quality of life (MusiQoL) questionnaires. Methods: Four hundred recruited RRMS patients were treated with human serum album free IFN β-1a for 1 year. Patients were required to fill in SF-36 and MusiQoL questionnaires at the first visit and at each follow-up visit. Expanded disability status scale (EDSS) evaluation was performed at baseline and at each visit. Comparisons in HRQoL between visits were calculated using Cohen's d effect size. The relationship between change in EDSS score and the score of each questionnaire was calculated using Pearson correlation coefficients. Results: Three-hundred and eighty three completed the study. Two-hundred and thirty nine were female. Mean (SD) age was 28.75 (±5.49). After 1 year, overall MusiQoL Index score effect size was ?0.16 and SF-36 physical component and mental component showed overall effect sizes of ?0.28 and ?0.53, respectively. Mean (range) EDSS change was 1 (1–4). Three-hundred and seventy four were clinically stable with mean (range) EDSS change of 0.1 (?2–0.5). Increase in EDSS was linked to a decrease in both MusiQoL and SF-36. Conclusion: We found that, HRQoL did not change significantly over the first year of therapy. Furthermore, decreases in HRQoL were inversely correlated with increases in EDSS score.     

Continuous subcutaneous apomorphine infusion does not impair the dynamics of cognitive action control in mild to moderate Parkinson’s disease

Introduction

Continuous subcutaneous apomorphine infusion (CSAI) is increasingly used in Parkinson’s disease (PD), notably in patients contraindicated for subthalamic deep brain stimulation. Although it has been suggested that CSAI is safe regarding cognition, few studies have actually investigated its effect, especially on cognitive control which is a crucial process for goal-directed behavior. More specifically, its impact on the dynamics of cognitive action control, as reflected by the activation and suppression of impulsive responses, has yet to be investigated, which is the objective of the present study.

Methods

We compared cognitive action control between baseline (M0) and 6 months (M6) after the start of add-on CSAI by administering an oculomotor Simon task to 20 patients with mild to moderate PD. We used the activation–suppression model to determine whether CSAI had an effect on either the impulsive errors made in conflict situations or the suppression of these responses.

Results

We found no difference between M0 and M6 in the congruence effect regarding either reaction time or accuracy, indicating that overall conflict resolution was not influenced by CSAI. Furthermore, the rate of fast errors in the conflict situation and the last slope of the delta plots (reflecting the strength of impulsive response suppression) were unaffected by the treatment. The 95% confidence intervals calculated for the treatment effect on both of these measures fell below the range of usual meaningful effects.

Conclusion

We found no difference between M0 and M6, which strongly suggests that CSAI does not impair the dynamics of cognitive action control.

     

Sumatriptan needle-free subcutaneous (Sumavel(®) DosePro™) approved for the acute treatment of migraine, with or without aura, and cluster headaches

Sumatriptan subcutaneous administration is the fastest and most effective of the triptans for relief of acute migraine headache. This occurs even when the patient has already developed symptoms related to central sensitization, a key parameter in determining the effectiveness of these agents. In patients whose migraine attacks have historically failed to respond to oral triptans, this route of administration has also proven to be more consistent and effective. Until recently this method of drug delivery was dependent upon a needle for administration. A new method of delivery for this agent, Sumavel(?) DosePro?, eliminates the needle and disposal issues coupled with an improved ease of use of drug delivery and acceptable tolerability for patients in clinical trials.     

Light and electron microscopic studies of “nude” mice CNS after subcutaneous administration of the E variant of the encephalomyocarditis (EMC) virus

Summary Sixteen 3 month old nude mice, 24 of their litter mates and 30 Swiss mice were injected subcutaneously with 0.1 ml suspension of the E variant of the encephalomyocarditis (EMC) virus. While the mortality rate of the litter mates and Swiss mice during 5–7 days after inoculation was more than 40%, none of the nude mice died during the experiment. The surviving animals were sacrificed at 24 h intervals from day one to seven days after injection. Brain suspensions assayed for the presence of the virus yielded significant titers at 24 h in all groups, which increased during 7 days. The litter mates and Swiss mice showed proliferation of lymphocytes and microglial cells in the perivascular areas of the brain during the fifth to the seventh day. The nude mice, on the other hand, displayed no perivascular lymphocytic infiltration during the same periods. Ultrastructurally, all groups showed aggregates of ribosomes in the cytoplasmic matrix on the third day, which became enlarged in size on the 5th day. At 7 days, both litter mates and Swiss mice showed an increased number of necrotic cells, while these changes were not observed in the nude mice. These findings suggest that the high mortality rate in immunologically normal mice was related to the efforts of T cells to eliminate virus-infected cells and to produce extensive necrosis, while T cell-depleted animals showed good survival rates.     

Patient subgroup analyses of the treatment effect of subcutaneous interferon β-1a on development of multiple sclerosis in the randomized controlled REFLEX study

The REFLEX study (NCT00404352) established that subcutaneous (sc) interferon (IFN) β-1a reduced the risks of McDonald MS (2005 criteria) and clinically definite multiple sclerosis (CDMS) in patients with a first clinical demyelinating event suggestive of MS. The aim of this subgroup analysis was to assess the treatment effect of sc IFN β-1a in patient subgroups defined by baseline disease and demographic characteristics (age, sex, use of steroids at the first event, classification of first event as mono- or multifocal, presence/absence of gadolinium-enhancing lesions, count of <9 or ≥9 T2 lesions), and by diagnosis of MS using the revised McDonald 2010 MS criteria. Patients were randomized to the serum-free formulation of IFN β-1a, 44 μg sc three times weekly or once weekly, or placebo, for 24 months or until diagnosis of CDMS. Treatment effects of sc IFN β-1a on McDonald 2005 MS and CDMS in the predefined subgroups were similar to effects found in the intent-to-treat population. McDonald 2010 MS was retrospectively diagnosed in 37.7 % of patients at baseline. Both regimens of sc IFN β-1a significantly reduced the risk versus placebo of McDonald 2005 MS and CDMS, irrespective of McDonald 2010 status at baseline (risk reductions between 29 and 51 %). The effect of sc IFN β-1a was not substantially influenced by baseline patient demographic and disease characteristics, or baseline presence/absence of McDonald 2010 MS.     

An autopsy case of a syndrome with muscular atrophy,decreased subcutaneous fat,skin eruption and hyper γ-globulinemia: peculiar vascular changes and muscle fiber degeneration

Summary This is the first autopsy case report of a syndrome with autosomal recessive inheritance, muscular atrophy, contracture, skin eruption, hyper -globulinemia, decreased subcutaneous fat, mental retardation and abnormal ECG findings. Skeletal muscles showed severe, discrete, multifocal muscular fibrosis which replaced several primary fasciculi. The tongue, heart and extraocular muscles showed identical but less severe findings. In the involved muscle fasciculi, veins and venules as well as arteries and arterioles showed medial hyperplasia and luminal constriction. Degeneration of endothelial cells of arterioles and narrowing of the lumen of terminal arterioles by the debris were observed. The peripheral nerves in the muscles were relatively well preserved. The correlation and pathogenesis of these findings are discussed.Supported in part by a Grant-in-Aid for Scientific Research (A) No. 60440046, from the Ministry of Education, Science and Culture, Japan     

Establishment of a multimodal protocol combining a motivational interview,subcutaneous injection of NicoSan® and hyper-hydration for the “stopsmoking therapy”: A multicentre real-life study’

ObjectivesThe StopSmoking Therapy, combins a motivational interview, a subcutaneous injection of NicoSan® and a hyperhydration protocol. The objectives were to evaluate the number of patients declaring cessation and factors related to relapse.MethodsIn the 18 months following protocol, 554 subjects who consented, responded to the study's questionnaire. Categorical variables are presented as the frequency and percentage, continuous variables are presented as the mean and standard deviation, responses of abstinent subjects and of those who had started smoking again are compared via the chi-square test for categorical variables, and the Student's t-test for continuous variables.ResultsIn our sample 92.8% of the subjects reported smoking for 10 years or more. A total of 475 subjects (85.7%) reported a complete cessation (31.2% for more than 6 months and 33.1% for more than a year). Among relapsing subjects, were significantly over-represented: youngest ages, lower motivation, more frequent close friends or family using tobacco, lower dependency scores. No subject reported any significant adverse effects.ConclusionThe multimodal protocol explored seems to have a favorable impact on smoking cessation, which could be enhanced by additional interventions dedicated to the youngest age groups, to people having smoking close friends and family, and should possibly add interventions based on cognitive behavioral therapy. A dedicated support by specialist tobacco addiction in the first weeks after treatment and/or the use of mobile support applications could also be useful. In order to asses efficacy, a prospective randomized double blind controlled versus placebo protocol could be considered.     

Temporal evolution of new T1-weighted hypo-intense lesions and central brain atrophy in patients with a first clinical demyelinating event treated with subcutaneous interferon β-1a

Journal of Neurology - Evaluate the effect of subcutaneous interferon β-1a (sc IFN β-1a) versus placebo on the evolution of T1-weighted MRI lesions and central brain atrophy in in...     

Safety profile of tinzaparin versus subcutaneous unfractionated heparin in elderly patients with impaired renal function treated for acute deep vein thrombosis: the Innohep® in Renal Insufficiency Study (IRIS)

Introduction

Trials comparing the use of full dose unfractionated heparin (UFH) or low molecular weight heparins (LMWHs) in very elderly patients with impaired renal function are lacking. IRIS aimed to assess whether LMWH is at least as safe as UFH in this population.

Materials and methods

The study included renally impaired patients ≥ 70 years with acute symptomatic lower limb deep vein thrombosis (DVT). Patients were randomized to initial treatment with either tinzaparin 175 IU/kg once daily (n = 269) or activated partial thromboplastin time-adjusted UFH twice daily (n = 270). After acute management both groups received vitamin K antagonist to day 90.

Results

The trial was stopped prematurely due to a difference in mortality favoring the UFH group (11.5 vs. 6.3%; p = 0.035). Rates of clinically relevant bleedings by day 90 were similar in the tinzaparin (11.9%) and UFH (11.9%) groups, as were rates of confirmed recurrent venous thromboembolism (VTE) (2.6 vs. 1.1%; p = 0.34). As the mortality difference could not be explained by bleedings or recurrent VTE, a post-hoc analysis was performed. This identified six baseline characteristics significantly correlated with mortality, of which five were over-represented in the tinzaparin group.

Conclusion

The IRIS study was a challenging study involving patients (mean age 83 years) usually excluded from clinical studies, but its early termination has left questions unanswered. The mortality difference observed with tinzaparin vs. UFH in elderly, renally-impaired patients with DVT cannot be explained on the basis of bleedings or recurrent VTE, and may reflect an imbalance of mortality risk factors at baseline.     

Efficacy of vitamin D3 as add-on therapy in patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon β-1a: a Phase II, multicenter, double-blind, randomized, placebo-controlled trial

Recent studies have demonstrated the immunomodulatory properties of vitamin D, and vitamin D deficiency may be a risk factor for the development of MS. The risk of developing MS has, in fact, been associated with rising latitudes, past exposure to sun and serum vitamin D status. Serum 25-hydroxyvitamin D [25(OH)D] levels have also been associated with relapses and disability progression. The identification of risk factors, such as vitamin D deficiency, in MS may provide an opportunity to improve current treatment strategies, through combination therapy with established MS treatments. Accordingly, vitamin D may play a role in MS therapy. Small clinical studies of vitamin D supplementation in patients with MS have reported positive immunomodulatory effects, reduced relapse rates and a reduction in the number of gadolinium-enhancing lesions. However, large randomized clinical trials of vitamin D supplementation in patients with MS are lacking. SOLAR (Supplementation of VigantOL(?) oil versus placebo as Add-on in patients with relapsing-remitting multiple sclerosis receiving Rebif(?) treatment) is a 96-week, three-arm, multicenter, double-blind, randomized, placebo-controlled, Phase II trial (NCT01285401). SOLAR will evaluate the efficacy of vitamin D(3) as add-on therapy to subcutaneous interferon beta-1a in patients with RRMS. Recruitment began in February 2011 and is aimed to take place over 1 calendar year due to the potential influence of seasonal differences in 25(OH)D levels.