Total syntheses of lysicamine, (±)-nuciferine, (±)-nornuciferine, (±)-zanthoxyphylline iodide, (±)-O-methylisothebaine, and (±)-trimethoxynoraporphine were accomplished by an approach that involves ...the formation of aporphine cores through reactions between an isoquinoline derivative and silylaryl triflates promoted by CsF. Unprecedented formations of aporphine cores proceeded in good yields presumably through 4 + 2 cycloaddition reactions followed by hydrogen migrations.
Polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis is a useful prognostic tool in multiple myeloma (MM), although its long-term impact still needs to be addressed. This ...report presents the updated results of the GIMEMA-VEL-03-096 trial. Thirty-nine MM patients receiving bortezomib-thalidomide-dexamethasone after autologous transplantation were monitored for MRD by both nested and real-time quantitative-PCR until relapse. Our data confirm the strong impact of MRD on survival: overall survival was 72% at 8 years median follow-up for patients in major MRD response versus 48% for those experiencing MRD persistence (P=0.041). In addition, MRD kinetics resulted predictive for relapse: indeed median remission duration was not reached for patients in major MRD response, 38 months for those experiencing MRD reappearance and 9 months for patients with MRD persistence (P<0.001). Moreover: (1) 26 patients achieving major MRD response (67%) benefit of excellent disease control (median TNT: 42 months); (2) MRD reappearance heralds relapse, with a TNT comparable to that of MRD persistence (9 versus 10 months, P=0.706); (3) the median lag between MRD reappearance and need for salvage treatment is 9 months. These results suggest the usefulness of a long-term MRD monitoring in MM patients and the need for maintenance or pre-emptive treatments ensuring durable responses.
: The number of elderly patients with epilepsy is growing in resource rich countries due to demographic changes and increased longevity. Management in these patients is challenging as underlying ...etiology, co-morbidities, polypharmacy, age-related pharmacokinetic and pharmacodynamic changes need to be considered.
: Lacosamide, eslicarbazepine acetate, brivaracetam, and perampanel have been approved in the USA and Europe for monotherapy and/or adjunctive treatment of seizures in the last few years. The authors review the pharmacological properties and safety profile of these drugs and provide recommendations for their use in in the elderly.
: There are only limited data available on more recent antiseizure medications (ASMs). Drugs with a low risk of interaction (lacosamide, brivaracetam) are preferred choices. Once daily formulations (perampanel and eslicarbazepine acetate) have the advantage of increased compliance. Intravenous formulations (brivaracetam and lacosamide) are useful in emergency situations and in patients who have difficulties to swallow. Dose adjustments are necessary for all ASMs used in the elderly with slow titration and lower target doses than in the regulatory trials. The adverse event profile does not significantly differ from that found in the general adult population.
Uruguay cuenta desde el año 2004 con una ley que tiene como objetivo la prevención, vigilancia y corrección de las situaciones de contaminación acústica. Sin embargo, pese a contar con casi dos ...décadas, dicha ley aún no ha sido reglamentada, por lo que existen diversos vacíos que deberían ser colmados para atender esta problemática, que afecta no sólo la salud de las personas, sino también la de otros seres vivos, y el ambiente. Pero además, si bien la contaminación acústica es uno de los grandes problemas que enfrenta nuestra sociedad, existe poco desarrollo doctrinario y jurisprudencial sobre la misma. El presente estudio intenta abordar la normativa existente sobre la contaminación acústica, así como los desafíos que enfrenta dicha problemática.
To investigate residual cholinergic and adrenergic responses to orthostatic stimulus in spinal cord injury, we evaluated 10 subjects with different outcome of traumatic (5) and inflammatory (5) ...spinal cord lesions between C6 and T10. The power spectra analysis of blood pressure and heart rate variability was performed during resting condition and head up tilt test. The difference between these two conditions was tested by using Wilcoxon signed rank test and the results were compared with control subjects. The typical decrease of HF power of R-R interval during posture changing was obtained only in the control subjects and in patients with paraplegia and incomplete lesions. In such conditions the SSR was always present at the plantar side. In complete lesions, the reduced decrease of HF is probably due to the down – regulation of vagal activity. In the same patients the absence of both heart rate and blood pressure LF peak are associated with the presence of some LF power of SBP. This seems to indicate the possibility of a LF generation either at a spinal level, without supraspinal control, or by other mechanisms, like the myogenic vasoconstrictor reflexes.
Highlights ► Fixation-off sensitivity (FOS) is characterized by the appearance of epileptiform discharges occurring after eyes-closure and lasting as long as the eyes are closed. ► FOS is induced by ...elimination of central vision/fixation. ► FOS is probably associated with occipital hyperexcitability but its intrinsic epileptogenic potential seems to be low.
The inability to stand without orthostatic hypotension is the typical disabling clinical symptom of both Postural Tachicardia Syndrome (POTS) and Orthostatic Intolerance (OI). The increase of sinus ...heart rate of 30 beats/min or greater occurring within 10 min of head-up tilt test or standing, or a heart rate while upright of >120 beats/min. discriminates between the two conditions. To verify if others criteria, beside the difference in heart rate increase, can distinguish the two groups, we analyzed the cardiovascular responses during active standing and head – up tilt test. We analyzed 10 patients with POTS and 10 with OI. Power spectral analysis of blood pressure and heart rate variability, in resting condition and during a period of 30 min of head – up tilt test to 60°, was performed. Both clinical conditions were compared with each other and with a control group using the Student t test. During the head – up tilt both groups of patients showed a marked and comparable increase of LF-RRI and LF/HF ratio in the power spectrum of R–R interval compared to the baseline. This could suggest the hypothesis of OI as a condition preceding POTS.
Lenalidomide has raised concerns regarding its potential impact on the ability to collect stem cells for autologous stem cell transplantation, especially after prolonged exposure. The use of ...cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells may overcome this concern. In newly diagnosed multiple myeloma (MM) patients, we investigated the influence of lenalidomide on stem cell collection. In a prospective study, 346 patients received four cycles of lenalidomide-dexamethasone (Rd). Stem cells were mobilized with cyclophosphamide and G-CSF. Patients failing to collect a minimum of 4 × 10(6) CD34(+)/kg cells received a second mobilization course. After mobilization, a median yield of 8.7 × 10(6) CD34(+)/kg was obtained from patients receiving Rd induction. After first mobilization, inadequate yield was observed in 21% of patients, whereas only 9% of patients failed to collect the target yield after the second mobilization attempt. In conclusion, we confirm that a short induction with lenalidomide allowed sufficient stem cells collection to perform autologous transplantation in 91% of newly diagnosed patients.
Neurosyphilis is rather an unusual cause of dementia characterized by a rapidly progressive course and psychiatric symptoms. Diagnosis of neurosyphilis should be suspected in the presence of a global ...cognitive impairment consisting in disorientation, amnesia and severe impairment of speech and judgement and psychiatric symptoms such as depression, mania and psychosis, with a subacute onset. More commonly, clinical manifestations of neurosyphilis include general PARESIS (involvement of Personality, Affect, Reflexes, Eye, Sensorium, Intellect and Speech). Upon clinical suspicion, diagnosis of neurosyphilis is confirmed by a reactive cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory. Here we report three Human Immunodeficiency Virus (HIV)-negative male patients presenting with psychiatric symptoms and a rapidly evolving dementia. Although magnetic resonance imaging did not address to diagnosis, CSF examination was mandatory in neurosyphilis diagnosis. Other diagnostic tools such as neuropsychology and single-photon emission computed tomography resulted supportive in the diagnosis. We showed that a prompt antibiotic treatment might stop disease progression. Therefore, neurosyphilis should be always considered even in HIV-negative patients in the presence of unexpected psychiatric symptoms accompanied by a rapidly evolving cognitive decline.
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