Intraspinal opiates for treatment of intractable pain in the terminally ill cancer patient

The discovery of opiate receptors and then their endogenous ligands in 1974 (Snyder et al., 1974) has elucidated a vast pharmacology of opiates providing a basis for their diverse clinical applications. With the awareness of quality of life as a primary goal in terminal cancer patients, widespread attention has been drawn to the direct delivery of long-term intraspinal analgesics to cancer patients for who all medical pain control regimens have failed (Coombs & Saunders, 1974). Intraspinal administration of opiates and nonopiate analgesics is not only appealing on theoretical grounds but provides a minimally invasive method to insure otherwise unobtainable pain relief while eliminating obtundation and systemic side-effects associated with conventional therapy (Cobb et al., 1984; Harbaugh et al., 1982; Leavens et al., 1982; Malone et al., 1985; Onofrie et al., 1981; Poletti et al., 1981). Although intraspinal opiates have been used in the treatment of postoperative and benign-pain syndromes (Asari et al., 1981; Cousins & Mather, 1984), in our discussion we review the basic science, current techniques and possible future improvements in spinal analgesia in the control of chronic cancer pain.     

Sustained attention training and errorless learning facilitates self‐care functioning in chronic ipsilesional neglect following severe traumatic brain injury

Limb activation studies involving contralesional spatiomotor cueing document a reduction of neglect for left space (Robertson & North, 1992, 1993, 1994; Samuel et al., 2000). A number of studies applying this approach have produced positive findings (Robertson, Hogg, & McMillan, 1998; Robertson, North, & Geggie, 1992; Robertson, McMillan, MacLeod, Edgeworth, & Brock, 2002; Samuel et al., 2000). An alternative theoretical approach which aims to facilitate spatial awareness via the modulation of non‐lateralised deficits in sustained attention/arousal (Robertson et al., 1997; Samuelsson et al., 1998) has also shown promising results (Robertson et al., 1995; Wilson, Manly, Coyle, & Robertson, 2000) in terms of improved contralesional unilateral neglect as well as activities of daily living.     

Visual orienting deficits in high-functioning people with autism

There has been renewed interest in the idea that attentional dysfunction may underlie autistic symptomatology (e.g., Bryson, Wainwright-Sharp, & Smith, 1990; Dawson & Lewy, 1989a, 1989b). Existing research indicates problems with overfocused attention (Lovaas et al., 1971; Rincover & Ducharme, 1987), and with shifting attention between sensory modalities (Courchesne et al., 1990). These phenomena were examined further by using Posner's (1978) visual orienting task with a group of high-functioning autistic adolescents and adults, and matched normal controls. Our results indicate that autistic people have difficulty processing briefly presented cue information. Evidence of problems disengaging and shifting attention within the visual modality was also provided. The findings can be seen as consistent with previous behavioral, autonomic, and electrophysiological research which has revealed impairments in the registration, processing, and response to external stimuli.This research was conducted in partial fulfillment of the first author's masters thesis. The work was supported by a Natural Science and Engineering Research Council grant awarded to Susan Bryson. We are grateful to the residents and staff of Woodview Manor, Hamilton, Ontario, and Kerry's Place, Aurora, Ontario, for their participation in this research.     

The modular architecture of the neglect syndrome: Implications for action control in visual neglect

In our recent review of action control deficits in hemispatial neglect we concluded that many patients with the disorder have deficits in visuomotor control [Coulthard, E., Parton, A., & Husain, M. (2006). Action control in visual neglect. Neuropsychologia, 44(13), 2717-2733]. This conclusion has been questioned and it has been argued instead that there are no action deficits in neglect [Himmelbach, M., Karnath, H.-O., & Perenin, M.-T. (2007). Action control is not affected by spatial neglect: A comment on Coulthard et al. Neuropsychologia, 45(8), 1979-1981]. We proposed that rather than being specific to the neglect syndrome, action control deficits are more likely to relate to lesion location. Although many of these impairments may contribute to the manifestation of neglect, they may also occur in brain-damaged patients without the condition. In this article, we explore this framework further, discussing how neglect behaviour may emerge from damage to a set of visuomotor or cognitive modules, or their connections. Central to our view is the idea that the critical combination of deficits leading to neglect varies considerably between cases, and that visuomotor or cognitive modules disrupted in the syndrome may not, in fact, be specific to neglect.     

Relapsing polychondritis with multifocal neurological abnormalities

A sixty-five year old woman developed relapsing polychondritis with three of the diagnostic criteria established by McAdam et al. (1976), namely bilateral auricular chondritis, ocular inflammation and both cochlear and vestibular dysfunction. Many authors have mentioned other neurological symptoms including unilateral facial weakness. This patient is the first case described with bilateral facial weakness and cerebral manifestations. Relapsing polychondritis, an uncommon, recurrent, inflammatory disorder affecting the cartilaginous tissues of the body (Jaksch-Wartenhorst, 1923; Herman, 1981), is regularly associated with audiovestibular dysfunction (Bollet et al., 1969; Cody et al., 1971; McAdam et al., 1976; Ridgway et al., 1979). McAdam et al. (1976) and Ridgway et al. (1979) have mentioned other neurological symptoms including unilateral facial weakness. We recently observed a patient with polychondritis and multifocal neurological abnormalities. We believe this is the first case described with bilateral facial nerve palsy and with cerebral manifestations.     

A molecular basis for interactions between the immune and neuroendocrine systems

Homeostatic and psychologic alterations associated with infections and tumors are very interesting yet poorly understood pathophysiologic responses. Numerous anecdotal and indirect examples suggest that these responses occur through a link between the central nervous and immune systems (for review see Blalock, Bost, & Smith, 1985; Spector & Korneva, 1981; Maestroni & Pierpaoli, 1981; Felton et al., 1985; Jankovic, 1985). Interactions between the two systems are just now being described. One possible mechanism is direct modulation of the immune system by the sympathetic nervous system. This could occur in innervated immune organs such as spleen, thymus, and bone marrow (Felton et al., 1985). The evidence for this is that sympathectomy and lesioning of specific regions of the brain can be shown to both enhance and/or suppress immune responses (Miles et al., 1985; Roszman et al., 1985). Also, the firing rate of hypothalamic neurons is altered during an immune response (Besedovsky et al., 1977). Alternatively, hormonal involvement in immune reactions has been known for some time, in particular the immunosuppressive effects of glucocorticoids (for review see Cupps & Fauci, 1982). Recently, we and others found that neuroendocrine peptide hormones will modulate T and B lymphocytes plus other immunocyte responses (Besedovsky et al., 1977; Cupps & Fauci, 1982; Johnson et al., 1982; Wybran et al., 1979; Hazum, Chang & Cuatrecasas, 1979; O'Dorisio et al., 1981; Gilman et al., 1982; McCain et al., 1982; Mathews et al., 1983; Plotnikoff et al., 1985; Johnson et al., 1984). Furthermore, lymphocytes themselves can synthesize biologically active neuroendocrine hormones (Blalock & Smith, 1980; O'Dorisio et al., 1980; Smith & Blalock, 1981; Smith et al., 1983; Lolait et al., 1984; Ruff & Pert, 1984), as well as possess specific hormone receptors (Blalock et al., 1985; Johnson et al., 1982; Wybran et al., 1979; Hazum et al., 1979; O'Dorisio et al., 1981; Lopker et al., 1980; Payan, Brewster & Goetzl, 1984; Pert et al., 1985). Immune responses (Besedovsky, del Rey & Sorkin, 1981), thymic hormones (Healy et al., 1983), and lymphokines (Lotze et al., 1985; Woloski et al., 1985) have all been shown to exert hormonal effects. Thus, another method for communication between the immune and neuroendocrine systems seems to be through soluble factors such as neuroendocrine hormones. This review will concentrate on the latter topic, in particular on work this laboratory has done over the past few years to show the lymphocyte production and immunoregulatory actions of neuroendocrine hormones.     

Oral coenzyme Q10 administration prevents the development of ischemic brain lesions in a rabbit model of symptomatic vasospasm

Treatment with oral coenzyme Q₁₀ (CoQ₁₀, 10 mg/kg per day for 6 days) was compared with no treatment in a previously described rabbit model of symptomatic cerebral vasospasm [Endo et al. (1988) Stroke 19: 1420–1425]. The treatment was initiated within 1–2 h after injection of autologous blood into the subarachnoid space. In CoQ₁₀-untreated rabbits, moderate to severe neurological deficits developed, and multiple focal ischemic lesions were found in the brain regions with compromised blood supply, i.e., in the regions normally supplied by common carotid arteries which are subject to ligation in this model. CoQ₁₀ treatment prevented the development of both the neurological deficits and histologically detectable brain tissue damage. In both CoQ₁₀-treated and -untreated rabbits, infiltration of mononuclear cells was evident in the brain stem, although this region did not show signs of ischemic damage. The findings indicate that the histological and neurological correlates of brain tissue damage in this rabbit model of symptomatic cerebral vasospasm develop via mechanism(s) involving free radical-mediated oxidation of plasma lipoproteins. Similar mechanisms may play a role in the development of brain damage attributed to cerebral atherosclerosis. Received: 11 December 1996 / Revised, accepted: 10 April 1997     

PTSD's underlying symptom dimensions and relations with behavioral inhibition and activation

Reinforcement sensitivity theory (RST) stipulates that individuals have a behavioral activation system (BAS) guiding approach (rewarding) behaviors (Gray, 1971, Gray, 1981), and behavioral inhibition system (BIS) guiding conflict resolution between approach and avoidance (punishment) behaviors (Gray & McNaughton, 2000). Posttraumatic stress disorder (PTSD) severity overall relates to both BIS (e.g., Myers et al., 2012, Pickett et al., 2011) and BAS (Pickett et al., 2011). Using a more refined approach, we assessed specific relations between PTSD's latent factors (Simms, Watson, & Doebbeling, 2002) and observed variables measuring BIS and BAS using 308 adult, trauma-exposed primary care patients. Confirmatory factor analysis and Wald chi-square tests demonstrated a significantly greater association with BIS severity compared to BAS severity for PTSD's dysphoria, avoidance, and re-experiencing factors. Further, PTSD's avoidance factor significantly mediated relations between BIS/BAS severity and PTSD's dysphoria factor.     

Patterns of math and reading achievement in children and adolescents with autism spectrum disorder

BackgroundThere has been an increase of autistic students without intellectual disabilities (autistic_WoID) placed in general education settings (Hussar et al., 2020), but there is a lack of understanding of how to best support classroom learning for these children. Previous research has pointed to subgroups of autistic_WoID children who display difficulty with mathematics and reading achievement (Chen et al., 2018; Estes et al., 2011; Jones et al., 2009; Wei et al., 2015). Research has primarily focused on symptomatology and communication factors related to learning in subgroups of autistic children. The current study sought to expand upon this research by assessing the validity of these previous studies and by investigating the specific contribution of domain-general cognitive abilities to differences in these subgroups.MethodSeventy-eight autistic_WoID individuals (M = 11.34 years, SD = 2.14) completed measures of mathematics and reading achievement, IQ, working memory, inferential thinking, and Theory of Mind (ToM). A hierarchical cluster analysis was performed on the math and reading measures.ResultsThe analysis revealed two unique achievement groups: one group that performed lower than expected on math and reading achievement and a second group that performed higher than expected. Groups differed significantly on IQ and working memory and were distinguished by performance on reading fluency. Groups did not differ on ToM, inferential thinking, or symptomatology.ConclusionThese findings describe a group of autistic_WoID individuals that may be more likely to experience difficulty learning, which should be accounted for in general education settings.     

A controlled crossover study of triiodothyronine in autistic children

A placebo-controlled crossover study of behavioral effects of triiodothyronine (T₃) was conducted in 30 young clinically euthyroid autistic children. Multiple independent raters and multiple rating scales were used. Except for a few symptoms that were reduced on T₃, the drug did not differ from placebo. Time itself accounted for most of the improvement in the whole sample. As a group, the lower IQ children responded to T₃. The individual children who were responders could not be defined by any parameter.This study was supported in part by Public Health Service Grant No. MH04665 from the National Institute of Mental Health. The authors wish to express their gratitude to Dr. Nancy Branom (Department of Radiology) and Dr. Ralph David (Department of Pediatrics) for their collaboration, to Mrs. Kathleen Nash, R.N., and Mrs. Sara Sol for their efforts in this study, and to Smith, Kline & French Laboratories for the medication supply.     

Autism and tuberous sclerosis

Autism is a behavior disorder with genetic influences indicated from twin and family studies and from the cooccurrence of autism with known genetic disorders. Tuberous sclerosis complex (TSC) is a known genetic disorder with behavioral manifestations including autism. A literature review of these two disorders substantiates a significant association of autism and TSC with 17–58% of TSC subjects manifesting autism and 0.4–3% of autistic subjects having TSC. In initial data collected on 13 TSC probands and 14 autistic probands in our family study of autism and TSC, we identified 7 TSC subjects with autism. The seven TSC autistic probands are similar to non-TSC autistic probands on the Social and Communication domains of the Autism Diagnostic Inventory (ADI) (Le Couteur et al., 1989), but show fewer Repetitive Rituals. There are more male TSC probands with autism than female, despite an equal sex ratio among TSC probands. The TSC probands with autism have significantly more seizures and mental retardation than those without autism; however, the extent and etiology of associations require further study. Our preliminary findings suggest that a fruitful approach for delineating genetic influences in autism may come from further investigation of possible mechanisms underlying the association of autism and TSC.This work was supported by an NIMH grant #1RO1MH44742-01 and by NIH grant #2RO1HD23745. We acknowledge Cathy Lord for her advice regarding the ADI and Robin Gilson for her help in data collection. We also thank all the family members who have participated in this project for their commitment and enthusiasm for this research.     

The effects of haloperidol on learning and behavior in autistic children

The effects of haloperidol on behavioral symptoms and learning were critically assessed in autistic children in an ongoing double-blind placebo-controlled clinical trial. Children were randomly assigned to haloperidol-placebo-haloperidol or placebo-haloperidol-placebo treatment sequences. Statistically, haloperidol was significantly superior to placebo in reducing behavioral symptoms. In discrimination learning paradigm, children receiving haloperidol learned the discrimination while those on placebo did not. Discrimination attained on haloperidol was retained when the children were switched to placebo.This study was supported in part by Public Health Service Grant MH-32212 from the National Institute of Mental Health. The authors wish to thank McNeil Pharmaceutical for supplying haloperidol and matching placebo tablets. Statistical analyses were performed by Dr. Ira L. Cohen. The special educational program to the children was provided by Mrs. Ruth Geelan, M.S., and Mr. Charles W. Hamilton. Part of this paper was presented at the III World Congress of Biological Psychiatry, June 28–July 3, 1981, Stockholm, Sweden, and was published in theProceedings of the Congress (B. Jansson, C. Perris, & G. Struwe, Eds.), Elsevier Biomedical Press, 1981.Dr. Caplan was in receipt of a special training grant from the American Jewish Joint Distribution Committee Inc., Israel.     

Chronic uncal herniation secondary to posterior fossa shunting: case report and literature review

Introduction  

Chronic herniation syndromes other than tonsillar herniation are not well-recognized. Transtentorial uncal herniation in its chronic form has been reported in only few case reports (Horowitz et al., J Neuroimaging 12:78–79, 2002; Naidich et al., Radiology 158:431–434, 1986; Ng and Valiante, J Clin Neurosci 16:944, 2009; Ng and Valiante, J Clin Neurosci 16:984, 2009). We hereby illustrate a case with this rare finding, including MR imaging, and analyze this phenomenon.     

Computerised cognitive behavioural therapy (cCBT): a possible treatment for mood disorders experienced by people with neurological conditions?

Mood disorders such as depression occur relatively often following the diagnosis of a range of neurological conditions. Recent studies reviewing the prevalence of depression amongst people with a neurological condition have shown that approximately one third report clinically significant levels of depression (Carson, Ringbauer, MacKenzie, Warlow, & Sharpe, 2000; Williams et al., 2003). In particular, people with a diagnosis of a cerebrovascular disorder or a neurological condition with additional cognitive impairments, have been found to be the most likely to report symptoms of depression (Williams et al., 2003). However, despite the evidence that a large proportion of people with neurological conditions experience mood disorders, there are currently limited resources available to treat them.     

Adaptive and maladaptive emotion regulation strategies: Interactive effects during CBT for social anxiety disorder

There has been a increasing interest in understanding emotion regulation deficits in social anxiety disorder (SAD; e.g., Hofmann, Sawyer, Fang, & Asnaani, 2012). However, much remains to be understood about the patterns of associations among regulation strategies in the repertoire. Doing so is important in light of the growing recognition that people's ability to flexibly implement strategies is associated with better mental health (e.g., Kashdan et al., 2014). Based on previous work (Aldao & Nolen-Hoeksema, 2012), we examined whether putatively adaptive and maladaptive emotion regulation strategies interacted with each other in the prediction of social anxiety symptoms in a sample of 71 participants undergoing CBT for SAD. We found that strategies interacted with each other and that this interaction was qualified by a three-way interaction with a contextual factor, namely treatment study phase. Consequently, these findings underscore the importance of modeling contextual factors when seeking to understand emotion regulation deficits in SAD.     

The neural basis of visuomotor deficits in hemispatial neglect

We have recently reported that patients with hemispatial neglect demonstrate increased terminal errors when performing delayed leftward reaches and that right-brain damaged patients (irrespective of neglect) take longer to complete their movements [Rossit, S., Muir, K., Reeves, I., Duncan, G., Birschel, P., & Harvey, M. (2009). Immediate and delayed reaching in hemispatial neglect. Neuropsychologiaa 47, 1563-1573]. Here we conducted an initial voxel-based lesion-symptom analysis to examine the neural basis of such deficits in 21 right-brain damaged subjects with 11 patients suffering from hemispatial neglect (2 more than in Rossit et al. [Rossit S., Muir K., Reeves I., Duncan, G., Birschel, P., & Harvey, M. (2009). Immediate and delayed reaching in hemispatial neglect. Neuropsychologia 47, 1563-1573] and 10 control patients without the condition. We found that the accuracy impairments in delayed leftward reaches were associated with damage to occipito-temporal areas. In contrast, the movement time slowing was related to more anterior lesions in the frontal lobe. These findings agree with the view that neglect affects actions thought to depend on the processing carried out by the ventral visual stream. In addition, we suggest that the timing impairments which are not neglect-specific maybe be driven by frontal structures.     

Diuretic abuse in eating disorders: Treatment protocol and case report

Abstract

Eating disorders are often complicated by the misuse of laxatives, diet pills, and diuretics. Although little attention has been paid to the problem of diuretic abuse as a method of weight control, diuretic abuse has been reported since 1968 in patients with anorexia nervosa (Wolff et al., 1968). A recent review article has documented the extent of diuretic use in eating disordered patients (Bulik, 1992). In a 1981 report of 34 bulimic patients, 29% (10 patients) reported having used diuretics for the purpose of weight control (Pyle, Mitchell,&Eckert, 1981). A subsequent 1985 study of 275 bulimic women found that 33.9% (90 women) used diuretics for weight loss reasons, 10.2% taking them at least once each day (Mitchell, Hatsukami, Eckert,&Pyle, 1985).     

Kinetic properties of recombinant MAO-A on incorporation into phospholipid nanodisks

Summary Recent structural studies of human monoamine oxidase A (MAO-A) suggest the entrance to the active site is positioned near the surface of the mitochondrial outer membrane (Colibus et al., 2005). To determine the influence of the phospholipid bilayer on the structure and catalytic properties of MAO in a defined system, we have incorporated the recombinant protein into phospholipid ‘nanodiscs’ which have been developed by Stephen G. Sligar’s group (Denisov et al., 2004). Purified MAO-A incorporates into pre-formed nanodiscs which are ∼10 nm in diameter and exhibit the thickness expected for a phospholipid bilayer. Nanodisc assemblies of MAO-A are water-soluble, yield increased enzyme stability relative to detergent solutions, are catalytically active, and reactive with acetylenic inhibitors. As compared to detergent-based systems, the catalytic efficiencies (k _cat/K _m) of amine oxidation appear to be greater. Also, nanodisc bound MAO-A binds various inhibitors with K _i values that are 2–4 fold lower than MAO-A in reduced Triton X-100 solutions. Taken together, these data suggest that the membrane environment affects MAO-A catalytic properties for both substrates and reversible inhibitors.     

Eye tracking technology: A fresh approach in delirium assessment?

The objective of this paper is to highlight the potential role of eye tracking technology (ETT) in the assessment of delirious patients. Delirium occurs in one in five general hospital admissions (Siddiqi, 2006) and its frequency will increase as society gets older. Despite its frequency and significant independent impact upon morbidity and mortality, delirium remains under studied and is frequently missed, detected late, or misdiagnosed (Farrell & Ganzani, 1995; Inouye, 2001; Kakuma, 2003). Detection is a key target for both clinical and research efforts. Assessment of attention is key to diagnosing delirium, yet nurses and non-research medical staff often fail to correctly identify inattention (Inouye et al., ; Lemiengre et al., ; Ryan et al., 2008). Eye tracking measures have been used in a plethora of key areas of psychiatric research (Crawford et al., ; Corden, Chilvers, & Skuse, 2008; Hardin, Schroth, Pine, & Ernst, 2007; Holzman, Leonard, Proctor, & Hughes, 1973), and provide an accurate and non-invasive method in the assessment of cognitive function. The potential of ETT for direct clinical applications in the assessment of attention and comprehension, key cognitive symptoms of delirium, are promising. This paper considers potential new approaches which recent advancements in non-invasive ETT may bring to the examination and understanding of delirium.