Amifampridine safety and efficacy in spinal muscular atrophy ambulatory patients: a randomized,placebo-controlled,crossover phase 2 trial

Journal of Neurology - Spinal muscular atrophy (SMA) is an autosomal recessive disease where a deficient amount of SMN protein leads to progressive lower motor neuron degeneration. SMN-enhancing...     

Anesthetics and automaticity in latent pacemaker fibers. III. Effects of halothane and ouabain on automaticity of the SA node and subsidiary atrial pacemakers in the canine heart.

Atrial tachyarrhythmias are a common manifestation of digitalis toxicity. Such arrhythmias could be due to enhanced automaticity of subsidiary atrial pacemakers (SAP) compared to the sinoatrial (SA) node. Halothane is known to oppose digitalis-induced ventricular arrhythmias. Its effect on digitalis-caused atrial arrhythmias is unknown. Therefore, we tested two hypotheses, as follows. First, increasing ouabain concentrations would enhance automaticity of SAP compared to the SA node and that such enhanced automaticity could explain digitalis-caused atrial tachyarrhythmias. Second, halothane would oppose such enhanced automaticity of SAP, thereby opposing digitalis-caused atrial tachyarrhythmias. A canine right atrial preparation was perfused via the SA node artery with Krebs' solution (36.0 +/- 0.5 degrees C) equilibrated with 97% oxygen-3% carbon dioxide. Four bipolar extracellular electrodes recorded the site of earliest activation (SEA), which in this preparation could be the SA node or increasingly remote sites of SAP approximately 1, 2, and 3 cm distal to the SA node along the sulcus terminalis. Pacemaker shifts to SAP during exposure to drugs were scored for magnitude of shift as 1, 2, or 3 depending on which SAP site was the SEA. Magnitude scores were summed for each test condition and normalized by dividing the total number of preparations tested. Preparations (n = 48) were exposed to 1 or 2% halothane (perfusate concentrations of 0.51 +/- 0.01 or 0.79 +/- 0.03 mM, respectively) and/or to low- or mid-therapeutic (2.5 or 5 x 10(-8) M) or borderline toxic ouabain (1 x 10(-7) M). Normalized magnitude scores were not significantly different from zero (control value) with any halothane or ouabain concentration alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute pancreatitis following azathioprine therapy of crohn's disease--a case report and the overview of the literature

Crohn's disease (CD) is the consequence of intestinal mucosa injury due to incorrect immune response to intestinal bacterial infection with lymphocyte T participation. Azathioprine--an immuno-modulator, is effective in the treatment and prevention of acute exacerbation of CD. It hinders the activity of immune cells, and therefore, the immune response. The use of azathioprine also reduces th necessity for corticosteroid therapy. Despite its efficacy, complications of azathioprine therapy are possible, including acute pancreatitis. In addition, acute pancreatitis is one of the extra-intestinal manifestations of acute exacerbation of CD without the previous use of azathioprine. We present a patient with acute pancreatitis, which occurred three weeks after the start of azathioprine treatment and manifested by clinical signs and symptoms similar to acute CD deterioration, and with elevated serum amylase and lipase levels. The symptoms responded rapidly to treatment with intravenous fluids, analgesics and azathioprine discontinuation after other possible causes were excluded. Thus, it is reasonable to estimate serum amylase and lipase levels frequently during 2 to 3 weeks after the start of azathioprine treatment for CD due to the possibility of acute pancreatitis occurring during this period in order to diagnose and treat acute pancreatitis as soon as possible, including early discontinuation of azathioprine therapy.     

One‐year follow‐up study of neuropathic pain in chronic inflammatory demyelinating polyradiculoneuropathy

We sought to gather information about frequency and features of neuropathic pain (NeP) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients and to investigate course of NeP during 1‐year follow‐up. Study included 105 patients diagnosed with CIDP. Patients with diabetes (N = 26) were excluded. NeP was diagnosed by the official guidelines and painDETECT questionnaire (PD‐Q). Medical Research Council Sum Score (MRC‐SS), INCAT disability and sensory scores, and Beck Depression Inventory were also measured. PD‐Q showed presence of NeP in 16 (20%) of 79 CIDP patients and their mean pain was moderate (5.1 ± 3.0 of 10). Diagnostic delay in CIDP patients with NeP was prolonged compared to CIDP patients without NeP (21 ± 28 vs 9 ± 12 months, P < .05). Slowly progressive course of the disease was more frequent in patients with NeP (81% vs 52%, P < .05). Patients with NeP had worse INCAT sensory score (P < .01), INCAT disability score (P < .05), MRC‐SS, as well as worse disease outcome at time of testing (P < .05). Depression was more common in patients with NeP (69% vs 17%, P < .01). During 1‐year follow‐up, majority of our CIDP patients had good control of NeP with gabapentinoids or amitriptyline. NeP was common in our cohort of non‐diabetic CIDP patients. It was associated with worse functional disability, worse sensory deficit, and depression. Special attention should be paid to CIDP patients with NeP because they request additional symptomatic therapy that appeared efficacious in our cohort.     

Acute and chronic pretreatment with essential oil of peppermint (Mentha × piperita L., Lamiaceae) influences drug effects

The appearance of common and self‐initiative usage of various herbal preparations in everyday practice and life imposes the question of possible interactions with drugs. This survey examined the influence of acute and chronic peppermint oil (PO – Mentha × piperita L., Lamiaceae; prepared as emulsion for oral use) on pentobarbitone‐induced sleeping time, analgesic effect of codeine and impairment of motor coordination caused by midazolam in mice. The chemical profile of essential oil was determined by GC‐MS. Applied doses of PO were 0.1 and 0.2 mL/kg. Chronic PO intake (in both doses) led to significant decrease of analgesic effect of codeine, while acute intake of PO did not change this effect. Acute PO pretreatment in higher dose caused significant prolongation of pentobarbitone‐induced sleeping time, while it was significantly shortened by chronic PO pretreatment at the same dose. Midazolam effect was enhanced and prolonged significantly by chronic PO intake at higher dose, while acute intake of PO did not change this effect. Gut motility was increased only by acute intake of higher PO dose. Regarding the fact that PO produces changes in tested drug effects, the interaction between drugs and phytopreparations containing PO should be additionally followed/confirmed in humans. Copyright © 2011 John Wiley & Sons, Ltd.     

What is the correlation between ratings and measures of olfactory function in patients with olfactory loss?

BACKGROUND: Major complaints of many patients with olfactory dysfunction relate to the impairment of quality of life. Nevertheless, it is unclear to what extent there is a correlation between ratings of olfactory abilities/impairment and olfactory function. METHODS: Patients with olfactory dysfunction (n = 152) were examined psychometrically using the "Sniffin' Sticks" test battery. Ratings of olfactory function and ratings of impairment were recorded using visual analog scales. RESULTS: Following standardized olfactory testing, 78 of the 152 patients were categorized as functionally anosmic, 64 as hyposmic, and 10 as normosmic. Groups differed significantly with regard to ratings of olfactory function. Functionally anosmic patients rated impairment to be significantly higher compared with hyposmic and normosmic patients. Ratings of olfactory function correlated significantly with measured olfactory function (r = +0.57) and ratings of impairment (r = -0.30). CONCLUSION: There was a moderate correlation between ratings and measures of olfactory function. On average, functionally anosmic patients recognized their olfactory loss, although, on an individual basis, there were striking differences between measures and ratings of olfactory function.     

CYP53A15 of Cochliobolus lunatus, a target for natural antifungal compounds

A novel cytochrome P450, CYP53A15, was identified in the pathogenic filamentous ascomycete Cochliobolus lunatus. The protein, classified into the CYP53 family, was capable of para hydroxylation of benzoate. Benzoate is a key intermediate in the metabolism of aromatic compounds in fungi and yet basically toxic to the organism. To guide functional analyses, protein structure was predicted by homology modeling. Since many naturally occurring antifungal phenolic compounds are structurally similar to CYP53A15 substrates, we tested their putative binding into the active site of CYP53A15. Some of these compounds inhibited CYP53A15. Increased antifungal activity was observed when tested in the presence of benzoate. Some results suggest that CYP53A15 O-demethylation activity is important in detoxification of other antifungal substances. With the design of potent inhibitors, CYP53 enzymes could serve as alternative antifungal drug targets.     

The impact of informed self-assessment on the development of medical students’ learning goals

Purpose: This study investigates the contributions of self-assessment (SA) and external feedback on the development of learning goals (LG) and the influence on LG recall and implementation in medical students.

Methods: Following a standardized patient (SP) assessment, 168 pre-clinical medical students completed a SA, received SP feedback and created a LG. LG were categorized by source. Two weeks later, students recalled LG and described implementation. Chi-squared analyses were used to test the associations.

Results: SA influenced LG for 82.8% of students whereas SP feedback influenced LG for 45.9%. Students rarely generated LG based on SA when they received discordant feedback (5.4%), but sometimes incorporated feedback discordant from their SA into LG (14.9%). Students who created LG based on SP feedback were more likely to recall LG than those who created LG based on SA, 89.7 versus 67.6%, p?2(1)?=?5.3, p?=?0.017. Students who reported receiving effective feedback were more likely to implement their LG than those reporting adequate feedback, 60.9 versus 37.9%, χ²(1)?=?8.0, p?=?0.01.

Conclusions: SA is an essential part of goal setting and subsequent action. Perception of feedback plays a crucial role in LG implementation.