Two stage Innoslab amplifier for energy scaling from 100 to >500 mJ for future lidar applications.

An Nd:YAG-MOPA system consisting of a stable oscillator and two subsequent Innoslab-based amplifier stages has been designed and built as a technology demonstrator for future lidar applications. Overall, the authors demonstrate that it generates more than 500 mJ of pulse energy at a 1064 nm wavelength and 100 Hz pulse repetition frequency at about 30 ns pulse duration in the single longitudinal mode. Seeded with 75 mJ pulses, the second amplifier stage achieved an optical efficiency (extracted energy to pump energy) of more than 23% while preserving excellent beam quality. To address the 500 mJ regime while retaining the basic system properties, an established Innoslab design was scaled geometrically.

kW-class direct diode laser for sheet metal cutting based on DWDM of pump modules by use of ultra-steep dielectric filters.

A direct diode laser was built with > 800 W output power at 940 nm to 980 nm. The radiation is coupled into a 100 µm fiber and the NA ex fiber is 0.17. The laser system is based on pump modules that are wavelength stabilized by VBGs. Dense and coarse wavelength multiplexing are realized with commercially available ultra-steep dielectric filters. The electro-optical efficiency is above 30%. Based on a detailed analysis of losses, an improved e-o-efficiency in the range of 40% to 45% is expected in the near future. System performance and reliability were demonstrated with sheet metal cutting tests on stainless steel with a thickness of 4.2 mm.

Oncology Association of Naturopathic Physicians: Principles of Care Guidelines.

Patient use of integrative oncology (the inclusion of nonconventional treatments alongside the conventional standard of care) continues to grow, with some studies showing its use in cancer patients to be as high as 91%. Naturopathic physicians are primary care providers who use integrative therapies to deliver patient-centred care. The Oncology Association of Naturopathic Physicians (oncanp) was formed in 2004 as a specialty association for naturopathic physicians providing integrative cancer care (nd oncs). Currently, the membership encompasses more than 400 naturopathic physicians and students, 115 of whom are board-certified Fellows of the American Board of Naturopathic Oncology. In 2016, oncanp established a committee comprising recognized experts in the field of naturopathic oncology to develop a Principles of Care (poc) guideline. The committee first undertook a review of existing standard-of-care and best-practice guidelines in the field of oncology and then adapted those concepts into a draft document. The draft document was then reviewed by naturopathic physicians, medical and radiation oncologists, naturopathic policy experts, and finally the oncanp membership at large. The poc document presented here provides clear guidelines for nd oncs on how best to deliver patient-centred care in the areas of assessment, treatment planning, care management, interprofessional collaboration, and survivorship care. This naturopathic oncology poc document can be a valuable resource for nd oncs and other oncology care providers to further an understanding of the naturopathic and integrative oncology care model and its potential for collaboration.

Modelling dementia: effects of scopolamine on memory and attention.

Scopolamine, a muscarinic cholinergic antagonist, is capable of inducing transient memory impairment in normal subjects. Against the background of the cholinergic hypothesis of Alzheimer's disease (AD) the present study was designed to investigate the effects of low oral doses of scopolamine on a range of cognitive functions known or hypothesized to be affected in AD. Twenty healthy volunteers (18-48 yr) performed a battery of automated cognitive tasks under each of five treatments: oral scopolamine 0.3 mg, 0.6 mg, 1.2 mg; oral methylscopolamine 0.6 mg; placebo. Alongside analogous tests of verbal and non-verbal memory, the battery enabled assessments of a range of attentional functions: alerting, sustained attention, selective attention, and covert orientation. A profile of effects was observed within and beyond the realm of memory. While some functions were unaffected by the drug (e.g. alerting) and others were impaired at the highest dose (e.g. verbal learning) still others were affected in a linear dose-dependent manner (sustained attention; visual contrast sensitivity). These observations are discussed in the context of the "scopolamine model" of AD.

Scopolamine and benzodiazepine models of dementia: cross-reversals by Ro 15-1788 and physostigmine.

The muscarinic antagonist scopolamine and the benzodiazepine lorazepam both produce transient impairments in memory and attention in normal volunteers. These impairments can be reversed by appropriate agents such as the cholinesterase inhibitor physostigmine in the case of scopolamine or the benzodiazepine antagonist Ro 15-1788 in the case of lorazepam. In this paper we investigated the pharmacological specificity of these reversals by examining the interactions of scopolamine and Ro 15-1788 and of lorazepam and physostigmine. There was no evidence that the effects of scopolamine and lorazepam on cognitive function could be attenuated by Ro 15-1788 and physostigmine, respectively. The results are discussed in terms of pharmacological models of Alzheimer's disease.

Effects of lorazepam on memory, attention and sedation in man: antagonism by Ro 15-1788.

In this study we examined the effects of lorazepam (2.0 mg PO) plus either placebo or one of three doses of the benzodiazepine antagonist Ro 15-1788 (0.3 mg, 1.0 mg or 3.0 mg IV) on measures of memory, attention and sedation. We found that lorazepam impaired verbal secondary memory performance, but also produced subjective and objective sedation; it increased reaction time, reduced critical flicker fusion thresholds and caused subjects to make more errors on a sustained attention task and rate themselves as drowsy. Ro 15-1788 dose dependently blocked the deficit in secondary memory produced by lorazepam, but also showed monotonic dose-related antagonism of its effects on indices of sedation (with the exception of the critical flicker fusion deficit, which was unaffected). These results demonstrate that lorazepam-induced cognitive deficits can be blocked by a benzodiazepine receptor antagonist. They also suggest that the memory deficits produced in this pharmacological model of organic amnesia are not readily dissociated from deficits in attention.

Effects of lorazepam on memory, attention and sedation in man.

The effects of three doses of lorazepam (0.5, 1.0 and 2.0 mg PO) on various aspects of memory, attention and sedation are described. Lorazepam produced dose-related deficits in verbal secondary memory, choice reaction time and a novel vigilance task. It also produced a dose-dependent increase in subjective sedation, and an enhancement of visual contrast sensitivity. These results are compared with those reported earlier using the muscarinic antagonist scopolamine, and discussed in relation to models of Alzheimer's disease.

Pentagastrin induced panic attacks: enhanced sensitivity in panic disorder patients.

The effects of pentagastrin, a synthetic analogue of the cholecystokinin tetrapeptide (CCK4), were studied in 15 patients with panic disorder and 15 healthy controls. Three different intravenous dosages of pentagastrin (0.1, 0.3 and 0.6 microgram/kg) and saline were investigated. Subjects were randomly allocated to two of the four treatment groups and tested on two separate occasions, 1 week apart, using an unbalanced double-blind incomplete block design. The mean panic rate with pentagastrin was 55% (12/22) for patients and 5% (1/22) for controls. None of the subjects panicked with saline. The frequency of panic attacks between the three pentagastrin doses in patients was not different. One control subject had a panic-like attack at the highest dose of pentagastrin. These findings concur with previous studies on the panicogenic effect of CCK4 and pentagastrin and suggest a greater sensitivity for CCK receptor agonists in patients suffering from panic disorder than in healthy controls.

Beta-endorphin: regional levels profile in the brain of the human infant.

Immunoradiometrical determinations of beta-endorphin (beta-EP) levels in 29 discrete brain regions from a series of victims of "Sudden Infant Death Syndrome" yielded a uniformly low levels profile in various areas of telencephalon, thalamus, pons, cerebellum and medulla oblongata. This low levels profile was interrupted by intermediate and high beta-EP levels in the midbrain and in two diencephalic zones. This study provides, for the first time, a comprehensive, neurochemically determined regional profile of beta-EP levels in the brain of the human infant.

Chronic untreated tuberculous meningitis.

We describe a 34-year-old man who suffered from tuberculous meningitis for 2 years without receiving antituberculous medication. Our case is compared with other forms of indolent or benign variants of the disease.

Brain-stem auditory evoked responses in diagnosis of central pontine myelinolysis.

Central pontine myelinolysis (CPM) developed in association with acute adrenocortical insufficiency during correction of severe hyponatraemia in a 58-year-old woman. Repeated CT scanning and NMR imaging were normal from the onset of the illness. Electroencephalography and brain-stem auditory evoked responses showed abnormalities consistent with a brain-stem lesion, which resolved as the patient made a gradual but incomplete recovery. Our observations illustrate the value of electrophysiological monitoring in CPM and support the proposed association between this condition and the rapid correction of an electrolyte imbalance.

The effects of chronic bromocriptine treatment on behaviour and dopamine receptor binding in the rat striatum.

Agonist-induced rotation and striatal binding of [3H]spiperone ([3H]SPIP) were assessed in rats with unilateral lesions of the substantia nigra during and after a period of chronic bromocriptine administration. Agonist-induced rotation significantly increased over a three week period of daily administration of bromocriptine (10 mg/kg i.p.); control animals were tested for agonist-induced rotation at one week intervals, which remained constant. Rotation was increased by chronic bromocriptine administration in response to either of two DA agonists, apomorphine (APO) and bromocriptine, suggesting that increased agonist sensitivity did not reflect a reduction in the metabolism of bromocriptine. Striatal binding of the dopamine D2 radioligand, [3H]SPIP, was significantly increased in the denervated striata of nigra-lesioned rats. Chronic bromocriptine administration decreased binding in denervated striata to levels not significantly different from control values. [3H]SPIP binding in intact striata was significantly reduced by bromocriptine to below control values. Differences in receptor levels reflected changes in the maximum density of binding sites with no change in affinities. Paradoxical behavioural hypersensitivity developing during chronic bromocriptine levels is not apparently mediated by changes in striatal D2 binding sites.

Reserpine-induced up-regulation of dopamine D2 receptors in the rat striatum is enhanced by denervation but not by chronic receptor blockade.

Compensatory increases in the density of dopamine (DA) D2 receptors in the rat striatum occur following chronic interruption of dopaminergic neurotransmission. Substantia nigra lesions, DA depletion with reserpine and D2 receptor blockade by neuroleptics increase the number of striatal D2 receptors as identified with the D2 ligand, [3H]spiperone [( 3H]SPIP). Chronic administration of haloperidol to substantia nigra-lesioned rats causes an additive increase in binding over levels obtained with one treatment alone. In this study we have found a similar response when lesioned animals are treated with reserpine. However, compensatory increases in the number of [3H]SPIP binding sites found after combined administration of reserpine and haloperidol to intact rats do not exceed levels obtained following administration of either drug alone. The data suggest that up-regulation of striatal D2 binding sites occurring after substantia nigra lesions is unique relative to other forms of up-regulation and may involve the loss of a presynaptic regulatory factor other than DA.

Chronic treatment with bromocriptine induces behavioral supersensitivity in rats.

Chronic treatment of rotating rats with equipotent doses of the dopamine (DA) agonists apomorphine (APO), 3-(3,4-dihydroxyphenyl)-1-n-propylpyrrolidine hydrobromide (DPPP) and bromocriptine (BRO) for four weeks resulted in marked differences in rotational activity following acute administration of these agonists. Whereas chronic treatment with APO and DPPP failed to produce any significant changes in agonist-induced rotational behavior, chronic BRO treatment induced a progressive increase in rotational activity up to a mean 200% increase over controls at four weeks. These findings may, in part, explain the long-term clinical efficacy of bromocriptine in patients with Parkinson's disease.

Lack of sedative and cognitive effects of diphenhydramine and cyclobenzaprine in elderly volunteers.

A double-blind, in-clinic, placebo-controlled, randomized, three-period crossover study was undertaken to investigate the potential sedative and cognitive effects of diphenhydramine 50 mg, p.o. and cyclobenzaprine 5 mg, p.o. in elderly volunteers. Subjects were given 10 doses of each treatment over a 4-day period according to a t.i.d. schedule. A battery of cognitive tests was administered 2 h after the first and last dose of each treatment period and subjects also completed visual analogue scale subjective ratings at regular intervals. There was no evidence that either drug caused drowsiness or affected cognitive test performance. These findings contrast with previous data using similar assessments in young volunteers, which indicated clear diphenhydramine-induced impairments. Contrary to commonly held belief, the elderly appear to be less sensitive than the young to the central nervous system effects of oral diphenhydramine.

The effects of pre-treatment with enalapril maleate on scopolamine-induced cognitive deficits in healthy volunteers.

Two studies were undertaken to investigate the effects of acute (Study 1) or repeated (Study 2) administration of the angiotensin converting enzyme (ACE) inhibitor enalapril on the cognitive deficits produced by scopolamine administration in volunteers. Enalapril at doses between 2.5 and 10.0 mg p.o. produced virtually complete blockade of plasma ACE activity. However, it did not influence the effects of scopolamine on a variety of cognitive tasks, including tests of memory, attention and sedation.

The scopolamine model of dementia: determination of central cholinomimetic effects of physostigmine on cognition and biochemical markers in man.

Administration of the muscarinic antagonist scopolamine has been proposed as a pharmacological model for Alzheimer's disease. We have attempted to characterize the cognitive deficits produced by the administration of scopolamine (0.2 and 0.4 mg intra muscularly) to normal volunteers. We have also demonstrated reversal of these deficits by the cholinesterase inhibitor physostigmine (1.2 mg intramuscularly). Physostigmine also elevated subjects' plasma ACTH levels, a marker of central cholinergic activity. In the cognitive study, we found that scopolamine impaired subjects' performance on verbal learning, spatial learning and choice reaction time. These changes were associated with subjective sedation as measured by analogue rating scales. Physostigmine attenuated the impairment in verbal learning and reduced subjective sedation. In the biochemical study we examined the effects of the same drug regimes on plasma ACTH levels. Physostigmine administered with a peripherally active cholinergic antagonist (glycopyrrolate 0.2 mg intramuscularly) produced a rise in ACTH level which reached a peak 30 min after drug administration. Such a rise was not apparent when the physostigmine was coadministered with scopolamine. These results suggest that cognitive and neuroendocrine indices of central cholinergic activity such as these may be useful in determining the effectiveness of potential new therapeutic agents for Alzheimer's disease.

The scopolamine model of dementia: chronic transdermal administration.

The transient impairments of memory produced by the muscarinic antagonist scopolamine have been adopted as a pharmacological model of Alzheimer-type dementia in normal volunteers. In this study we examined the effects of chronic (72 h) transdermal administration of scopolamine on memory, attention, sedation and visual function. The transdermal patches provided constant plasma levels of scopolamine for the duration of the study. Indices of the peripheral effects of scopolamine (visual near-point and pupil size) showed impairments that were sustained for 3 days. However, measures of sedation and memory revealed impairments that were maximal the day after patch application and which were no longer present 3 days after application. This pattern of results is discussed in relation to pharmacological modelling of Alzheimer's disease.

Stridor and obstructive sleep apnea in Shy-Drager syndrome treated by laryngofissure and cord lateralization.

A patient with obstructive sleep apnea due to Shy-Drager syndrome, who has been successfully managed by cord lateralization, is presented. This has allowed successful rehabilitation of the patient without prejudicing subsequent surgery, and appears to be an effective procedure in this rare condition.

Neuropsychological investigation of anterior and posterior cortical function in early-stage probable Alzheimer's disease.

In vivo neuroimaging studies have generally indicated a greater involvement of posterior cortical areas in early-stage dementia of the Alzheimer type (DAT) relative to frontal involvement. By contrast, some recent neuropsychological studies have shown that DAT patients perform poorly in frontal lobe tasks even in the early stages of the disease, although there is disagreement as to whether this necessarily implicates frontal pathology. The main aim of this study was to examine the hypothesis prompted by both neuroimaging studies and the traditional clinical conception of the disease, that, compared with the functioning of posterior association cortex, executive functions (thought to depend on frontal lobe integrity) are relatively spared in the early stages of DAT. A group of patients with a diagnosis of early-stage, probable DAT (n = 17) was compared with age- and IQ-matched controls (n = 17) across a range of neuropsychological tasks presumed to exercise frontal or temporoparietal functions. A profile of strengths and weaknesses was observed across 'anterior' and 'posterior' cognitive tests, including dissociations among some tests of temporoparietal function, in particular visual object perception (impaired) and spatial analysis skills (intact). Thus there was little support for the notion that the disease progresses cortically in a posterior-to-anterior direction. Possible reasons for the discrepancy between neurophysiological and neuropsychological observations are discussed, including the possibility that neuropsychological tests do not provide a valid indication of regional brain function when used in the context of DAT. Caution is urged in the clinical application of 'frontal lobe tests' for the differential diagnosis of DAT.