Summary Background In the 24-month MS-STAT phase 2 trial, we showed that high-dose simvastatin significantly reduced the annualised rate of whole brain atrophy in patients with secondary progressive ...multiple sclerosis (SPMS). We now describe the results of the MS-STAT cognitive substudy, in which we investigated the treatment effect on cognitive, neuropsychiatric, and health-related quality-of-life (HRQoL) outcome measures. Methods We did a secondary analysis of MS-STAT, a 24-month, double-blind, controlled trial of patients with SPMS done at three neuroscience centres in the UK between Jan 28, 2008, and Nov 4, 2011. Patients were randomly assigned (1:1) to either 80 mg simvastatin (n=70) or placebo (n=70). The cognitive assessments done were the National Adult Reading Test, Wechsler Abbreviated Scale of Intelligence, Graded Naming Test, Birt Memory and Information Processing Battery (BMIPB), Visual Object and Space Perception battery (cube analysis), Frontal Assessment Battery (FAB), and Paced Auditory Serial Addition Test. Neuropsychiatric status was assessed using the Hamilton Depression Rating Scale and the Neuropsychiatric Inventory Questionnaire. HRQoL was assessed using the self-reported 36-Item Short Form Survey (SF-36) version 2. Assessments were done at study entry, 12 months, and 24 months. Patients, treating physicians, and outcome assessors were masked to treatment allocation. Analyses were by intention to treat. MS-STAT is registered with ClinicalTrials.gov , number NCT00647348. Findings Baseline assessment revealed impairments in 60 (45%) of 133 patients on the test of frontal lobe function (FAB), and in between 13 (10%) and 43 (33%) of 130 patients in tests of non-verbal and verbal memory (BMIPB). Over the entire trial, we noted significant worsening on tests of verbal memory (T score decline of 5·7 points, 95% CI 3·6–7·8; p<0·0001) and non-verbal memory (decline of 6·8 points, 4·8–8·7; p<0·0001). At 24 months, the FAB score was 1·2 points higher in the simvastatin-treated group than in the placebo group (95% CI 0·2–2·3). The simvastatin group also had a 2·5 points better mean physical component score of the SF-36 (95% CI 0·3–4·8; p=0·028). A treatment effect was not noted for any other outcomes. Interpretation To our knowledge, this SPMS cohort is the largest studied to date with comprehensive longitudinal cognitive, neuropsychiatric, and HRQoL assessments. We found evidence of a positive effect of simvastatin on frontal lobe function and a physical quality-of-life measure. Although we found no effect of simvastatin on the other outcome measures, these potential effects warrant confirmation and underline the importance of fully assessing cognition and quality of life in progressive multiple sclerosis treatment trials. Funding The Moulton Foundation, the Berkeley Foundation, the Multiple Sclerosis Trials Collaboration, the Rosetrees Trust, a personal contribution from A W Pidgley CBE, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre and University College London.
Objective This study evaluated the effects of photodynamic therapy (PDT) on buccal candidiasis in mice and on the adherence of yeast to buccal epithelial cells (BECs) in vitro. Study Design A total ...of 56 immunosuppressed mice with buccal candidiasis were subjected to PDT, consisting of treatment with erythrosine (400 μmol/L) followed by exposure to a green LED (14.34 J cm–2 ). After treatment, the yeasts recovered from the mice were quantified (CFU/mL) and analyzed for the effects of PDT on their adherence to BECs. The data were analyzed using ANOVA, the Tukey test, Kruskal-Wallis test and Student t test. Results PDT significantly reduced the amount of yeast present in the lesions by 0.73 log10 ( P = .018) and reduced C. albicans adherence to BECs by 35% without damaging adjacent tissues ( P = .045). Conclusions Photodynamic therapy exhibited antifungal effects against C. albicans biofilms formed in vivo and reduced the capacity of C. albicans to adhere to BECs in vitro.
Abstract Objective The aim of the study was to review clinical, imagiologic, and surgical outcomes of tracheal resection in the management of laryngotracheal stenosis. Methods The study used a ...retrospective analysis of adult patients managed in a tertiary academic hospital who underwent thyrotracheal, cricotracheal, or tracheal end-to-end anastomosis between 1997 and 2006. Results Twelve patients, aged 15 to 79 years old, were included. Prolonged tracheal intubation was the leading cause of stenosis (11 patients) that was classified according to Myer-Cotton ( Ann Otol Rhinol Laryngol . 1994;103:319–323) classification as follows: grade II (25%), grade III (58%), and grade IV (17%). The stenosis extension ranged from 1 to 6cm. Surgeries varied from tracheal end-to-end anastomosis (n = 5), cricotracheal anastomosis (n = 4), and thyrotracheal anastomosis (n = 3). Extubation was achieved in 11 patients (92%). One patient maintains a T tube stent. The most common complication was the presence of granulation tissue in the anastomosis region (33%). There was no mortality associated. Conclusions Tracheal resection with primary anastomosis appears to be a successful and safe procedure mainly due to its high decannulation rate and few complications associated.
This study evaluated the action of propolis and intracanal medications against Escherichia coli and endotoxin. Forty-eight dental roots were contaminated with E. coli . The root canals were ...instrumented with propolis and divided into groups according to the type of intracanal medication: Ca(OH)2 , polymyxin B, or Ca(OH)2 + 2% chlorhexidine gel. In the control group, saline solution was used without application of intracanal medication. Counts of colony-forming units were carried out and the endotoxin was quantified by the chromogenic Limulus amobocyte lysate assay. The results were evaluated by analysis of variance and the Dunn test (5%). Root canal irrigation with propolis was effective to completely eliminate E. coli and reduce the amount of endotoxins. All intracanal medications contributed to the significant decrease in endotoxins. Only intracanal medications may reduce the amount of endotoxins in the root canals. The greatest efficacy was observed for medications containing Ca(OH)2.
Objective This study evaluated the effects of photodynamic therapy on pathogenicity of Candida albicans. Study design Fifty-six rats were submitted to development of candidiasis on the tongue dorsum ...by C. albicans inoculations. After 5 days, different treatments were administered: laser and photosynthesizer methylene blue (L+P+); laser only (L+P−); photosensitizer only (L−P+); and physiologic solution only (L−P−). Samples of the oral cavity were collected for a count of colony-forming units per mL. Colonies were isolated for evaluation of proteinase and phospholipase activities. The rats were killed for microscopic analysis of the tongue dorsum. The data were analyzed by analysis of variance, Kruskal-Wallis, and Bonferroni tests. Results The number of C. albicans recovered from the oral cavity of the rats was similar between the groups ( P = .106). The L+P+ group showed fewer microscopic lesions of candidiasis than the L−P− group ( P = .001). The L+P+ group presented lower proteinase activity compared with the other groups, with significant difference between the groups L+P+ and L−P+ ( P = .018). Conclusions Photodynamic therapy reduced the microscopic lesions of experimental candidiasis in rats and inhibited the proteinase activity of C. albicans.
Objective The purpose of this study was to evaluate the effects of endodontic irrigants on the microhardness of root canal dentin. Study design Thirty extracted single-rooted human teeth were used. ...The crowns were sectioned at the cementoenamel junction. Each root was transversely sectioned into cervical, middle, and apical segments, resulting in 90 specimens. The 3 sections of each root were separately mounted in an individual silicon device with acrylic resin. The specimens were randomly divided into the following 3 groups (n = 30), according to the irrigant solution used: (1) group 1, control (saline solution); (2) group 2, 2% chlorhexidine gluconate solution; and (3) group 3, 1% sodium hypochlorite (NaOCl). After 15 minutes of irrigation, dentin microhardness was measured on each section at 500 μm and 1000 μm from the pulp-dentin interface with a Vickers diamond microhardness tester in Vickers hardness number (VHN). Results Data obtained were analyzed using analysis of variance and the Tukey test (5%). Specimens irrigated with 2% chlorhexidine (group 2) or 1% NaOCl (group 3) presented lower values of dentin microhardness, with significant difference in relation to the control group ( P < .05). Conclusion It could be concluded that chlorhexidine and NaOCl solutions significantly reduced the microhardness of root canal dentin at 500 μm and 1000 μm from the pulp-dentin interface.
Summary Background Frontotemporal dementia is a highly heritable neurodegenerative disorder. In about a third of patients, the disease is caused by autosomal dominant genetic mutations usually in one ...of three genes: progranulin ( GRN ), microtubule-associated protein tau ( MAPT ), or chromosome 9 open reading frame 72 ( C9orf72 ). Findings from studies of other genetic dementias have shown neuroimaging and cognitive changes before symptoms onset, and we aimed to identify whether such changes could be shown in frontotemporal dementia. Methods We recruited participants to this multicentre study who either were known carriers of a pathogenic mutation in GRN, MAPT , or C9orf72 , or were at risk of carrying a mutation because a first-degree relative was a known symptomatic carrier. We calculated time to expected onset as the difference between age at assessment and mean age at onset within the family. Participants underwent a standardised clinical assessment and neuropsychological battery. We did MRI and generated cortical and subcortical volumes using a parcellation of the volumetric T1-weighted scan. We used linear mixed-effects models to examine whether the association of neuropsychology and imaging measures with time to expected onset of symptoms differed between mutation carriers and non-carriers. Findings Between Jan 30, 2012, and Sept 15, 2013, we recruited participants from 11 research sites in the UK, Italy, the Netherlands, Sweden, and Canada. We analysed data from 220 participants: 118 mutation carriers (40 symptomatic and 78 asymptomatic) and 102 non-carriers. For neuropsychology measures, we noted the earliest significant differences between mutation carriers and non-carriers 5 years before expected onset, when differences were significant for all measures except for tests of immediate recall and verbal fluency. We noted the largest Z score differences between carriers and non-carriers 5 years before expected onset in tests of naming (Boston Naming Test −0·7; SE 0·3) and executive function (Trail Making Test Part B, Digit Span backwards, and Digit Symbol Task, all −0·5, SE 0·2). For imaging measures, we noted differences earliest for the insula (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume was 0·80% in mutation carriers and 0·84% in non-carriers; difference −0·04, SE 0·02) followed by the temporal lobe (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume 8·1% in mutation carriers and 8·3% in non-carriers; difference −0·2, SE 0·1). Interpretation Structural imaging and cognitive changes can be identified 5–10 years before expected onset of symptoms in asymptomatic adults at risk of genetic frontotemporal dementia. These findings could help to define biomarkers that can stage presymptomatic disease and track disease progression, which will be important for future therapeutic trials. Funding Centres of Excellence in Neurodegeneration.
In 69 statin-treated male coronary patients with low-density lipoprotein cholesterol at goal levels (<70 mg/dl), the investigators tested whether low high-density lipoprotein (HDL) cholesterol (<40 ...mg/dl) and high triglyceride (>150 mg/dl) are associated with dysfunctional HDL particles and abnormal insulin, adiponectin, C-reactive protein serum levels. Thirty-four patients with low HDL cholesterol and high triglyceride (dyslipidemia) and 35 patients with low-density lipoprotein cholesterol, HDL cholesterol, and triglyceride at target levels (normolipidemia) were studied. Twenty healthy men were also studied. High-sensitivity C-reactive protein was measured using immunonephelometry, insulin using a radioimmunometric assay, and total adiponectin by enzyme-linked immunosorbent assay. Cell cholesterol efflux to serum and total isolated HDL was assayed using rat hepatoma Fu5AH cells for scavenger receptor class B type 1–mediated efflux. Compared to the normolipidemia and healthy groups, and after adjustment for age and waist circumference, patients with dyslipidemia showed higher fasting insulin (14, 9.9, and 8.5 μU/ml, respectively), homeostasis model assessment of insulin resistance values (3.4, 2.3, and 1.8, respectively), lower adiponectin concentrations (5.1, 8.1, and 11 μg/ml, respectively), and reduced cholesterol efflux to serum (14%, 15%, and 19%, respectively) and to HDL fractions (4.4%, 4.6%, and 5.6%, respectively) (p <0.05 for all variables). Multivariate analysis showed that adiponectin and apolipoprotein A1 accounted for 10.7% and 3.9%, respectively, of the variance in cholesterol efflux. In conclusion, the decreased cholesterol efflux and metabolic abnormalities found in the dyslipidemia group may contribute to the residual risk observed in the large statin trials and the higher morbidity and mortality in statin-treated coronary patients with low HDL cholesterol even when attaining low-density lipoprotein cholesterol <70 mg/dl.
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