Relative dynamic muscular endurance of patients with neuromuscular disorders and of healthy matched control subjects

This study was undertaken to determine whether the relative muscular endurance of patients with paresis secondary to neuromuscular disorders was different from that of comparable healthy persons. Using an isokinetic dynamometer, I measured the peak knee extension torque of five patients with neuromuscular disorders and of five matched controls. Torque was measured during an initial and 40 subsequent maximal knee extensions at 180 degrees/sec. Gravity-corrected peak torques of the initial repetition and every fifth subsequent repetition were compared between groups, as were the percentages of decrease in torque (calculated relative to the initial torque) using two-way analysis of variance procedures. The results of these procedures demonstrated that the healthy subjects were significantly stronger than the patients with paresis (p less than .01) but that the patients had significantly better relative muscular endurance (ie, smaller percentages of decrease in torque) than the healthy subjects (p less than .05). These findings suggest that, for the patients tested, the relative muscular endurance of patients with paresis is not compromised. This finding does not preclude patients with paresis being unable to complete multiple repetitions of specific functional tasks requiring some critical level of muscular strength.     

Randomized double-blind placebo-controlled study of an angiotensin immunotherapeutic vaccine (PMD3117) in hypertensive subjects

Immunization against components of the renin-angiotensin system offers a potential alternative to daily medication in some patients with hypertension or heart failure. Our primary objective was to determine whether a sustained antibody titre to Ang I (angiotensin I) can be achieved in hypertensive patients. The secondary objective was to determine whether the antibodies block the renin system. Patients (n=27) with essential hypertension responsive to an ACEi (angiotensin-converting enzyme inhibitor) or ARB (angiotensin blocker) were randomly assigned to receive three or four injections of the Ang I vaccine PMD3117 or aluminium hydroxide (Alhydrogel trade mark ) over a 6 week period. Antibody titre was measured prior to each injection and every 30 days until disappearance. Indices of renin blockade were changes in renin and aldosterone (blood and urine) and a within-patient comparison of the pre- and post-vaccination rise in 24 h ambulatory blood pressure after 2 weeks of withdrawal of ACEi or ARB. The anti-(Ang I) antibody titre rose from the second injection in both regimes and peaked on day 64. Median half-life was 85 (95% CI, 44 and 153) days (where CI is confidence interval). Vaccination did not influence blood pressure, but significantly blunted the fall in plasma renin following withdrawal of ACEi or ARB. At 42 days after the first injection, aldosterone excretion was decreased by PMD3117 to 6 (95% CI, 1 and 31)% of values in patients receiving Alhydrogel trade mark (P=0.012). In patients with essential hypertension, PMD3117 generated a prolonged antibody response to Ang I. Biochemical measurements show evidence of blockade of the renin system, but higher titres will be required to achieve a decrease in blood pressure.     

Double-blind, placebo-controlled study of oxacillin combined with rifampin in the treatment of staphylococcal infections.

A total of 101 patients with proven Staphylococcus aureus infection were included in a double-blind, placebo-controlled study; this study compared oxacillin (12 g/day, intravenously) or vancomycin (2 g/day, intravenously) plus rifampin (1,200 mg/day, orally) with oxacillin or vancomycin plus placebo. We evaluated 65 patients. Of the patients tested, 33 received oxacillin plus rifampin (13 bacteremias), and 32 received oxacillin plus placebo (16 bacteremias). Clinical cure was achieved in 61% of the patients treated with oxacillin plus rifampin and in 56% of the patients treated with oxacillin plus placebo. Improvement was noted in 27 and 25%, respectively, and failure occurred in 9 and 18%, respectively. These differences were not statistically significant. Bacteriological failure occurred in 3 and 28%, respectively (P less than 0.05). None of the failures within the rifampin-treated group was associated with the emergence of a rifampin-resistant mutant. The rates of superinfection were similar in both groups. The geometric means of the serum bactericidal activity after 1, 6, and 11 h were, respectively, 22, 17, and 9 after treatment with oxacillin plus rifampin and 25, 3.4, and 2.3 after treatment with oxacillin plus placebo. It was suggested that the addition of rifampin to oxacillin or vancomycin might only be beneficial to severely ill patients.     

Biomechanical properties of low back myofascial tissue in younger adult ankylosing spondylitis patients and matched healthy control subjects

BackgroundAnkylosing spondylitis is a degenerative and inflammatory rheumatologic disorder that primarily affects the spine. Delayed diagnosis leads to debilitating spinal damage. This study examines biomechanical properties of non-contracting (resting) human lower lumbar myofascia in ankylosing spondylitis patients and matched healthy control subjects.MethodsBiomechanical properties of stiffness, frequency, decrement, stress relaxation time, and creep were quantified from 24 ankylosing spondylitis patients (19 male, 5 female) and 24 age- and sex-matched control subjects in prone position on both sides initially and after 10 min rest. Concurrent surface electromyography measurements were performed to ensure resting state. Statistical analyses were conducted, and significance was set at p < 0.05.FindingsDecreased lumbar muscle elasticity (inverse of decrement) was primarily correlated with disease duration in ankylosing spondylitis subjects, whereas BMI was the primary correlate in control subjects. In ankylosing spondylitis and control groups, significant positive correlations were observed between the linear elastic properties of stiffness and frequency as well as between the viscoelastic parameters of stress relaxation time and creep. The preceding groups also showed significant negative correlations between the linear elastic and viscoelastic properties.InterpretationFindings indicate that increased disease duration is associated with decreased tissue elasticity or myofascial degradation. Both ankylosing spondylitis and healthy subjects revealed similar correlations between the linear and viscoelastic properties which suggest that the disease does not directly alter their inherent interrelations. The novel results that stiffness is greater in AS than normal subjects, whereas decrement is significantly correlated with AS disease duration deserves further investigation of the biomechanical properties and their underlying mechanisms.     

Flexor carpi radialis motoneuron pool in subjects with chronic carpal tunnel syndrome are more excitable than matched control subjects

We compared excitability of the flexor carpi radialis (FCR) motoneuron pool in subjects with and without carpal tunnel syndrome (CTS). The study involved 11 subjects with chronic idiopathic CTS and 11 asymptomatic subjects as controls. The H-reflex and M-response of FCR muscle were obtained by stimulating the median nerve in the cubital fossa in the presence of an isometric background contraction using surface stimulating and recording electrodes. There was a significantly higher H-reflex latency and amplitude and Hmax/Mmax in CTS subjects (P<0.05). Latency and amplitude of the M-response remained unaffected in CTS group. The results support the hypothesis that central hypersensitivity does occur in chronic CTS. Therefore even in the presence of pathology in peripheral structures central mechanisms should be considered by clinicians.     

Double-blind placebo-controlled trial of baclofen, alone and in combination, in patients undergoing voluntary abortion

This study evaluated the analgesic efficacy of baclofen in relation to specific pain stimuli in 83 women (27 nulliparas and 56 multiparas) undergoing voluntary abortion (clamping of the cervix and dilatation and curettage). The patient population was divided into five treatment groups as follows: group 1, placebo; group 2, baclofen, 0.3 mg/kg, administered intravenously (IV); group 3, baclofen, 0.6 mg/kg IV; group 4, baclofen, 0.3 mg/kg IV, and fentanyl, 1.5 mg IV; and group 5, baclofen, 0.3 mg/kg IV, and diazepam, 5 mg given orally and 5 mg IV. In each case the surgical intervention was started using analgesia only. When the first sensation of pain was recorded, a paracervical anesthetic block was performed to provide pain relief for completion of the operation. The results showed that baclofen had significantly better analgesic properties than did placebo, with no important side effects. Its analgesic action seemed to be dose-dependent, since better results were obtained with the higher dose. The analgesic effect was slightly potentiated when baclofen was combined with fentanyl, but not when it was combined with diazepam. Factors independent of the pain stimuli and drugs used--the most important being parity--influenced the results.     

Cerebrolysin改善缺血性脑卒中患者神经功能和生活能力的随机双盲研究

目的:评价Cerebrolysin对缺血性脑卒中后早期、恢复期的临床疗效。方法:对60例缺血性脑卒中患者在早期恢复期行随机、双盲及安慰剂对照的前瞻性研究。分为Cerebrolysin组(A组)和安慰剂组(B组),以临床神经功能缺损量表(CSS)、简易智力状态量表(MMSE)、日常生活能力量表(ADL)、总的生活能力状态(TLS)的变化为评价指标;并以副反应量表(DOTES和TWIS)评定药物的副反应。结果:60例患者脱落2例(脱落率3%,2/60),剔除1例(剔除率2%1/60)。治疗后两组间比较,MMSE评分治疗组优于对照组(22.2±5.比22.0±6.6,P=0.0314)。其他3项量表差异无显著性意义。组内治疗前后比较:CSS(A组:23.7±6.3比15.1±8.8;B组:25.2±6.8比16.0±8.1);ADL(A组:46.3±7.0比39.6±12.8;B组:45.7±9.4比39.7±11.6);TLS(A组:4.4±0.8比3.7±1.3;B组:4.5±0.8比3.5±1.3);MMSE(A组:17.8±5.2比22.2±5.6;B组22.0±7.0比22.0±6.6),差异均有非常显著性意义。结论:Cerebrolysin对缺血性卒中后早期恢复期的认知功能的恢复有益。     

Double-blind placebo-controlled study with interleukin-18 and interleukin-12-encoding plasmid DNA shows antitumor effect in metastatic melanoma in gray horses

Melanoma is a disease with high incidence in gray horses and has limited therapeutic options in metastatic disease. Gene therapy has shown some success in animal models and human patients. A randomized double-blind, placebo-controlled study was conducted to investigate 2 treatment options using cytokine-encoding plasmid DNA in horses with metastatic melanoma to induce immunologic antitumor effects. Adult gray horses with spontaneously occurring metastatic melanoma (n=26) were included in the study. Treatment of 26 gray horses with metastatic melanoma consisted of interleukin-18-encoding plasmid DNA, interleukin-12-encoding plasmid DNA, or empty plasmid DNA (control group), injected intratumorally, respectively. Tumor response was assessed using ultrasound and caliper measurements and histologic assessment of tumor biopsies. Significant tumor regression could be shown in both the treatment groups receiving IL-18 and IL-12-encoding plasmid DNA whereas placebo-treated control patients showed tumor growth over the course of the treatment. In addition, 7 of 10 tumors from horses treated with IL-18 or IL-12 showed peritumoral and/or intratumoral inflammatory infiltrates after treatment compared with 1 of the 6 in the control group. The treatment as assessed by serial blood draws and clinical investigation, was safe and well tolerated. These data suggest that the intratumoral treatment with IL-18 and IL-12-encoding plasmid DNA has antitumor effects, which is well tolerated and thus holds promise for the treatment of patients with metastatic melanoma.     

Double-blind,placebo-controlled study of the efficacy and tolerability of nimesulide administered orally in acute bronchial asthma

In this double-blind, placebo-controlled study, children with acute exacerbation of bronchial asthma between the ages of 1 and 12 years not responding to conventional therapy with bronchodilators and injectable steroids were enrolled. A total of 60 children (two groups of 30 each) was studied. The overall response to therapy was assessed based on the guidelines and recommendations of the National Heart, Lung and Blood Institute. The efficacy parameters included respiratory and heart rates, degree of dyspnea, accessory muscle usage, color, wheeze, and degree of oxygen saturation. Children with moderate to severe exacerbation received either nimesulide suspension 1.5 mg/kg per dose or identical placebo orally as per random protocol. To assess the clinical progress, all the efficacy parameters were reassessed after 30 minutes and 1, 2, and 6 hours. A significant difference was observed in the overall assessment of response at 1, 2, and 6 hours in the two treatment groups. A greater number of children showed a good overall response in the nimesulide group compared with the placebo group at 1, 2, and 6 hours (P <.01). No side effects were reported in any of the patients in either group. None of the patients was withdrawn prematurely from either group. It is evident from the current study that nimesulide showed good efficacy and tolerability. Therefore, nimesulide could be administered to asthmatic patients whenever there is a need for such therapy.     

Active music therapy in the treatment of multiple sclerosis patients: a matched control study

Twenty multiple sclerosis patients (14 female, 6 male) were involved in the study, their ages ranging rom 29 to 47 years. Ten participants formed the therapy group, and 10 the control group. The groups were comparable on the standard neurological classification scheme Expanded Disability Status Scale (EDSS). Exclusion criteria were pregnancy and mental disorders requiring medication. Measurements were taken before therapy began (T1), and subsequently every 3 months (T2-T4). This battery included indicators of clinical depression and anxiety (Beck Depression Inventory and Hospital Anxiety and Depression Scale), a self-acceptance scale (SESA) and a life quality assessment (Hamburg Quality of Life Questionnaire in Multiple Sclerosis). In addition, data were collected on cognitive (MSFC) and functional (EDSS) parameters. Patients in the therapy group received 3 blocks of music therapy in single sessions over the course of the one year project (8 to 10 sessions respectively). The music therapy approach used for this study is based on the Nordoff Robbins approach (Nordoff & Robbins, 1977). There was no significant difference between the music therapy treatment group and the control group. However, the effect size statistics comparing both groups show a medium effect size on the scales measuring self esteem (d = 0.5423, r =.026), depression HAD-D (d = 0.63, r = 0.310) and anxiety HAD-A (d = 0.63, r = 0.310). Significant improvements were found for the therapy group over time (T1-T4) in the scale values of self esteem, depression, and anxiety. Given the stigmatizing effect of a chronic degenerative disease, the positive benefits of music therapy point to a realm of aesthetic considerations in assessing clinical improvement.     

Clinical implications of gait analysis in the rehabilitation of adult patients with "Prader-Willi" Syndrome: a cross-sectional comparative study ("Prader-Willi" Syndrome vs matched obese patients and healthy subjects)

Background  

Being severely overweight is a distinctive clinical feature of Prader-Willi Syndrome (PWS). PWS is a complex multisystem disorder, representing the most common form of genetic obesity. The aim of this study was the analysis of the gait pattern of adult subjects with PWS by using three-Dimensional Gait Analysis. The results were compared with those obtained in a group of obese patients and in a group of healthy subjects.     

Results of the glucose-lowering effect of WelChol study (GLOWS): a randomized, double-blind, placebo-controlled pilot study evaluating the effect of colesevelam hydrochloride on glycemic control in subjects with type 2 diabetes

OBJECTIVE: This study evaluated the glycosylated hemoglobin (HbA(1c)-lowering effect of colesevelam hydrochloride, a bile acid sequestrant, in subjects with type 2 diabetes that was inadequately controlled by existing antihyperglycemic therapy. METHODS: After a 4-week placebo run-in period, subjects with type 2 diabetes and an HbA(1c) value of 7.0% to 10.0% were randomized to receive colesevelam 3.75 g/d or matching placebo for 12 weeks. Subjects' previous oral anti hyperglycemic medication (sulfonylurea and/or metformin) was continued throughout the study. Fasting blood samples were obtained at weeks -5, -1, 0, 1, 4, 8, and 12. The primary efficacy end point was the change in HbA(1c) from baseline to week 12. Secondary end points included changes in fructosamine levels, fasting plasma glucose levels, postprandial glucose level, and meal glucose response (ie, difference between preprandial and postprandial levels), and percent changes in lipid parameters from baseline to week 12. RESULTS: The 65 randomized subjects (31 colesevelam, 34 placebo) had a mean age of 56.2 years and a mean body mass index of 32.4 kg/m(2); 55.4% were male and 53.8% were white. The difference in least squares (LS) mean (SE) change in HbA(1c) between the colesevelam group and the placebo group was -0.5% (0.18) (P = 0.007). In subjects with a baseline HbAIc > or = 8.0%, the difference in LS mean change in HbA(1c) was -1.0% (0.27) (P = 0.002). Relative to placebo, colesevelam treatment was associated with reductions in levels of fructosamine (-29.0 [10.9] pmol/L; P = 0.011) and postprandial glucose (-31.5 [13.6] mg/dL; P = 0.026). The mean percent change in low-density lipoprotein cholesterol was -9.6% in the colesevelam group, compared with 2.1% in the placebo group (treatment difference, -11.7% [4.2]; P = 0.007); the respective mean percent changes in total cholesterol were -4.0% and 3.4% (treatment difference, -7.3% [3.0]; P = 0.019). Colesevelam also was associated with significant decreases in the percent change in apolipoprotein B (P = 0.003) and low-density lipoprotein particle concentration (P = 0.037). The incidence of treatment-emergent adverse events (TEAEs) was similar in both groups, although treatment-related adverse events were more frequent in the colesevelam group than in the placebo group (29.0% vs 8.8%, respectively). The most frequent TEAEs in the colesevelam group were gastrointestinal disorders (22.6%), primarily constipation (19.4%), compared with an 8.8% incidence of gastrointestinal disorders (0% constipation) in the placebo group. There were no significant changes in body weight or the occurrence of hypoglycemia between treatment groups. CONCLUSIONS: In these subjects with type 2 diabetes, 12 weeks of colesevelam treatment were associated with significant reductions in HbA(1c) and in fructosamine and postprandial glucose levels compared with placebo. The 2 groups had a similar adverse-event profile, with the exception of an increased incidence of constipation in the colesevelam group. These results suggest that colesevelam may improve both lipid control and glycemic control in patients with type 2 diabetes receiving oral antihyperglycemic medications.     

A double-blind placebo-controlled study of an infusion of lexipafant (Platelet-activating factor receptor antagonist) in patients with severe sepsis

Platelet-activating factor (PAF) is a potent endogenous proinflammatory mediator implicated in the pathogenesis of septic shock. A double-blind randomized placebo-controlled trial of an intravenous PAF receptor antagonist (lexipafant) was conducted with 131 adult Thai patients with suspected severe sepsis (66 of whom had positive blood cultures). Detailed serial clinical, biochemical, and cytokine measurements were performed. Lexipafant treatment was well tolerated. The 28-day mortality in the lexipafant group (61.4%) was similar to that in the placebo group (62.6%). There was also no evidence that lexipafant affected clinical or biochemical measures of disease severity or the profile of sequentially measured plasma cytokine levels. PAF may not have an important role in the pathogenesis of severe sepsis.