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As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.

Gregory S Tentindo,1 Scott M Fishman,2 Chin-Shang Li,3 Qinlu Wang,4 Steven D Brass5,6 1Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, CA, USA; 2Department of Anesthesiology, Division of Pain Medicine, University of California Davis, Sacramento, CA, USA; 3Department of Public Health Sciences, Division of Biostatistics, University of California Davis, Sacramento, CA, USA; 4Department of Statistics, University of California Davis, Davis, CA, USA; 5Department of Neurology, University of California Davis, Sacramento, CA, USA; 6Department of Administration, Providence Little Company of Mary Medical Center San Pedro, San Pedro, CA, USA Purpose: Some patient subsets are at higher risk of sleep apnea, including patients with chronic pain. However, it is unclear whether patients and their caregivers are aware of the possibly increased risk of sleep apnea in this population. Chronic pain is often treated with opioids which may decrease both the central respiratory drive and the patency of the upper airway, potentially contributing to this sleep disorder. Using a self-reporting questionnaire approach in the chronic pain population, this study surveyed patient and caregiver awareness surrounding the risk of sleep apnea. In addition, we looked at the influence of opioid therapy on the prevalence of sleep apnea. Participants and methods: Consecutive patients presenting to a pain clinic were invited to participate anonymously in a survey that included the STOP-Bang sleep apnea questionnaire, which assesses patients’ knowledge, testing, diagnosis, or treatment of sleep apnea and whether their caregivers had discussed with them their increased risk of sleep apnea and opioid use. Results: Among 305 participating patients, 58.2% (n=173) screened positive for sleep apnea. Among the 202 patients on opioid therapy, 59.2% (116/202) were STOP-Bang positive (score ≥3). However, only 37.5% (n=72/173) of these patients had discussed their risk of sleep apnea with a caregiver and only 30.7% (n=59) underwent testing. Against expectation, opioids did not increase the prevalence of sleep apnea in our study population. Conclusion: Chronic pain patients had a high risk of sleep apnea, regardless of opioid prescription. Most patients were unaware of their increased risk and denied undergoing the necessary testing. Greater attention to screening, testing, and education for sleep apnea needs to be paid in chronic pain patients, especially given the potentially dangerous ramifications of opioid-induced sleep apnea. Keywords: sleep apnea, opioids, narcotics, STOP-Bang survey

A Patient Safety Huddle was developed at a community hospital (Providence Little Company of Mary Medical Center, San Pedro, California) through consultation with key stakeholders. The goal was to become a high reliability organization by improving communication across different departments, troubleshooting operational problems, focusing on safety and quality metrics, and reporting unusual occurrences. The Patient Safety Huddle involved executives in development and implementation, respect for employee time, ensuring accountability, and empowering frontline staff to foresee and deal with safety issues. The current template of the Patient Safety Huddle agenda and the Documentation Tools used to address patient safety issues are provided.

Background: Hand eczema is a common inflammatory dermatosis that causes significant patient morbidity. Previous studies comparing psoralen–ultraviolet A (PUVA) with narrowband ultraviolet B (NB‐UVB) have been small, nonrandomized and retrospective. Objectives: To conduct an observer‐blinded randomized controlled pilot study using validated scoring criteria to compare immersion PUVA with NB‐UVB for the treatment of chronic hand eczema unresponsive to topical steroids. Methods: Sixty patients with hand eczema unresponsive to clobetasol propionate 0·05% were randomized to receive either immersion PUVA or NB‐UVB twice weekly for 12 weeks with assessments at intervals of 4 weeks. The primary outcome measure was the proportion of patients achieving ‘clear’ or ‘almost clear’ Physician's Global Assessment (PGA) response at 12 weeks. Secondary outcome measures included assessment of the modified Total Lesion and Symptom Score (mTLSS) and the Dermatology Life Quality index (DLQI). Results: In both treatment arms, 23 patients completed the 12‐week assessment for the primary outcome measure. In the PUVA group, five patients achieved ‘clear’ and eight ‘almost clear’ [intention‐to‐treat (ITT) response rate 43%]. In the NB‐UVB group, two achieved ‘clear’ and five ‘almost clear’ (ITT response rate 23%). For the secondary outcomes, median mTLSS scores were similar between groups at baseline (PUVA 9·5, NB‐UVB 9) and at 12 weeks (PUVA 3, NB‐UVB 4). Changes in DLQI were similar, with improvements in both groups. Conclusions: In this randomized pilot trial recruitment was challenging. After randomization, there were acceptable levels of compliance and safety in each treatment schedule, but lower levels of retention. Using validated scoring systems – PGA, mTLSS and DLQI – as measures of treatment response, the trial demonstrated that both PUVA and NB‐UVB reduced the severity of chronic palmar hand eczema.

Study Objectives:To report at a population level the prevalence of restless legs syndrome, insomnia, and the risk of obstructive sleep apnea in multiple sclerosis patients. Sleep patterns and assoc...

Background: Recent evidence has shown that mitochondrial dysfunction may be significant in carriers of the Fragile X premutation. Purpose: The present study examined fatigue severity and body mass index (BMI) (two possible outcomes related to mitochondrial dysfunction) in premutation carriers with and without the Fragile X-associated Tremor Ataxia Syndrome (FXTAS) as compared to controls. Methods: Surveys to gather data on height and weight and fatigue impact (Fatigue Severity Scale) were sent out to previous research trial participants with Fragile X premutation-related disorders. Results: On the Fatigue Severity Scale, carriers with and without FXTAS had mean scores of 4.5 (SD 1.9) and 3.8 (SD 1.6), respectively, that differed significantly (p

The Patient Safety Subcommittee requested a review of the science and policy issues regarding the rapidly emerging public health epidemic of prescription opioid-related morbidity and mortality in the United States. Over 100,000 persons have died, directly or indirectly, from prescribed opioids in the United States since policies changed in the late 1990s. In the highest-risk group (age 35–54 years), these deaths have exceeded mortality from both firearms and motor vehicle accidents. Whereas there is evidence for significant short-term pain relief, there is no substantial evidence for maintenance of pain relief or improved function over long periods of time without incurring serious risk of overdose, dependence, or addiction. The objectives of the article are to review the following: (1) the key initiating causes of the epidemic; (2) the evidence for safety and effectiveness of opioids for chronic pain; (3) federal and state policy responses; and (4) recommendations for neurologists in practice to increase use of best practices/universal precautions most likely to improve effective and safe use of opioids and to reduce the likelihood of severe adverse and overdose events. Neurology® 2014;83:1277–1284

This study examined the relationship between the fragile X premutation and restless legs syndrome (RLS). Demographic, medical history and survey responses related to sleep were collected from 213 participants (127 carriers and 86 age matched controls). Subjects were asked about the presence of the four formal diagnostic criteria for RLS. Individuals with the premutation were 1.9 times as likely to meet criteria for RLS (95% CI 1.1–3.2, p=0.025) as controls. Premutation carriers with RLS also experienced significantly worse symptoms than matched controls with adjusted mean scores of 15.1±8.8 vs 7.9±4.4, respectively on the International Restless Legs Scale (IRLS). As markers for domains of sleep disturbance, all subjects completed the Epworth Sleepiness Scale (ESS), the Insomnia Severity Index (ISA) and the Pittsburgh Sleep Quality Index (PSQI). Premutation carriers demonstrated significantly more pathology on these tests except for the ESS where there was a trend towards increased daytime sleepiness in carriers. RLS joins a host of other conditions that should be carefully screened for in those carrying the fragile X premutation and sleep should be a focus for clinicians providing care to them.

This study aims: (1) to identify patients with multiple sclerosis (MS) who are at high risk for obstructive sleep apnea (OSA) by utilizing the STOP-BANG questionnaire and (2) to evaluate the relationship between OSA risk as determined by the STOP-BANG questionnaire and self-reported sleepiness and fatigue using the Epworth Sleepiness Scale (ESS) and the Fatigue Severity Scale (FSS), respectively.A total of 120 consecutive patients presenting to the UC Davis Neurology MS Clinic were invited to participate in an anonymous survey. The exclusion criteria were: age18 years, indefinite MS diagnosis, or incomplete survey.There were 103 subjects included in our study: 42% of subjects (n = 43) met the criteria for high-risk OSA, 69% of subjects (n = 71) screened high for fatigue (FSS ≥ 4), but only 24 subjects (23%) screened high for excessive daytime sleepiness (ESS 10). In males, 44% of the variation in ESS scores and 63% in FSS scores were explained by the STOP-BANG components. However, only 17% of the variation in ESS scores and 15% of the variation in FSS scores was explained by the STOP-BANG components in females.Over 40% of MS patients were identified as high risk for OSA based on the STOP-BANG questionnaire. The STOP-BANG questionnaire offers clinicians an efficient and objective tool for improving detection of OSA risk in MS patients.

Injurious feather pecking in non-cage systems is a serious economic and welfare concern for the egg-producing industry. Here, we describe the first results from an ongoing collaborative project to improve range environment and welfare of laying hens(Gallus gallus domesticus)within the McDonald's Restaurants Ltd, UK supply base. The objective of this study was to investigate, in a commercial situation, the correlation between: i) proportion of range cover and ii) proportion of canopy cover, with plumage damage of end-of-lay hens. The assessment of plumage damage due to injurious feather pecking is a key animal-based welfare indicator for laying hens in non-cage systems. In 2007 and 2008, all laying-hen producers within the McDonald's Restaurants Ltd egg-supply base, were required to plant (if not present already), 5% of the total range area with blocks of trees ether side, and between 20-25 m from the laying hen house. Plumage damage at end of lay was positively correlated with mortality and flocks depleted in summer had less plumage damage at end of lay than flocks depleted in autumn or winter, possibly because of weather conditions at the time of placement. There was no correlation between the proportion (5-90%) of range cover and plumage damage at the end of lay, however, plumage damage was negatively correlated with percent of canopy cover within tree-planted areas. Providing a minimum of 5% tree cover, planted close to the house but with good canopy coverage, may be a feasible and practical method enabling producers to reduce plumage damage due to injurious feather pecking in their laying-hen flocks. Tree cover provision may also provide environmental benefits, such as soil stabilisation, reduced nutrient leaching and carbon sequestration.

Patients with multiple sclerosis (MS) often have unrecognized sleep disorders at higher frequency than the general population. Sleep disorders such as sleep disordered breathing, insomnia, REM sleep behavior disorder, narcolepsy and restless legs syndrome have all been reported in the MS population. Notably, the most common symptom of MS is "fatigue," which itself has been correlated with sleep disturbances. Sleep disorders may impact the quality of life of the MS patient population. This paper reviews the association of sleep disorders with MS, and discusses the association of sleep disruption with MS fatigue.

A 46-year-old man presented to this hospital with migraine headache, a 4-year history of neurologic events resulting in aphasia and hemiparesis, and a family history of two similarly affected brothers. Neuroimaging studies showed white-matter and deep gray-matter abnormalities. A diagnostic test was performed.

Conventional brain MRI lesion measures have unreliable associations with clinical progression in multiple sclerosis (MS). Gray matter imaging may improve clinical-MRI correlations.We tested if gray matter MRI measures and conventional measures of lesions/atrophy predicted clinical progression in a 4-year longitudinal study of 97 patients with MS. Baseline and follow-up brain MRI were analyzed for basal ganglia and thalamic normalized T2 signal intensity, whole brain T2-hyperintense lesion volume, and whole brain atrophy. Logistic regression tested the ability of baseline or on-study change in MRI to predict disability progression, as reported by area under the receiver operator characteristics curve (AUC).Lower caudate T2-intensity at baseline (P= .04; AUC = .69) and on-study decreasing T2-intensity in the putamen (P= .03; AUC = .70) and thalamus (P= .01; AUC = .71) were the MRI variables associated with clinical progression when regression modeling was adjusted for length of follow-up interval, baseline EDSS, disease duration, age, and sex.Gray matter T2-hypointensity, suggestive of excessive iron deposition is associated with worsening disability in patients with MS. Gray matter MRI assessment may be able to capture neurodegenerative aspects of the disease, with more clinical relevance than derived from conventional MRI measures. J Neuroimaging 2009;19:3-8.

A 59-year-old man was admitted to this hospital with a 6-month history of chronic daily headache, fever, and myalgia. Dry mouth, polydipsia and polyuria, and pain in the jaws on chewing developed. Neuroimaging studies showed diffuse thickening and enhancement of the dura, extending to the pituitary stalk. Computed tomography revealed calcified nodules in the lungs and spleen. A diagnostic procedure was performed.

IL-15 is a pro-inflammatory cytokine whose three-dimensional structure is similar to that of IL-2. IL-2 and IL-15 have similar as well as distinct biological functions. An active form of IL-15 that is membrane bound has also been described. Furthermore, IL-15 is known to play a role in autoimmune diseases. We thus investigated the expression of membrane bound IL-15 on monocytes (CD14+ cells) and studied its effect on T cell activation in MS patients. We found that unstimulated CD14+ cells from relapsing remitting MS patients had increased membrane bound IL-15. Those with high surface levels of IL-15 on monocytes were in the early stages of the disease. In addition, we found that T cells of MS patients had enhanced responsiveness to IL-15 and there was increased expression of IL-15 receptor on CD4+ T cells. Thus, IL-15 may be an important cytokine that drives Th1 responses early in the course of the disease and could serve as a target for immunotherapy and as an early marker in the immunologic staging of MS.

Pregnancy can precipitate new neurological diseases as a result of the alterations in physiology that accompany the pregnant state. The pregnant patient presenting with neurological problems poses both diagnostic and therapeutic challenges, often forcing the clinician to rely on neuroimaging as part of the workup. This review discusses potential risks to the embryo and fetus posed by computed tomography (CT) and magnetic resonance imaging (MRI), the imaging studies most often used to study the central nervous system. Imaging features of a variety of neurological conditions associated with pregnancy are discussed, including pre-eclampsia and eclampsia, Wernicke's encephalopathy, cerebral venous thrombosis, ischemic stroke, postpartum angiopathy, and lymphocytic hypophysitis.

We review the anatomy of the frontal scalp in relation to the clinical features and surgical management of frontalis-associated lipoma. Awareness of this entity, coupled with sound regional anatomical knowledge, is essential to achieve good outcomes.

We assessed axonal injury and demyelination in the cerebral normal-appearing white matter (NAWM) of MS patients in a pilot study using proton magnetic resonance spectroscopic imaging and quantitative magnetization transfer (MT) imaging. Resonance intensities of N-acetylaspartate (NAA) relative to creatine (Cr) were measured in a large central brain volume. NAA/Cr in NAWM was estimated by regression of the NAA/Cr in each voxel against white matter fraction and extrapolation to a white matter fraction of 1. The fractional size of the semi-solid pool (F) was obtained from the binary spin bath model of MT by computing the model parameters from multiple MT-weighted and relaxometry acquisitions. F in NAWM was significantly smaller in the patients [0.109 (0.009)] relative to controls [0.123 (0.007), P = 0.011], but did not differ between RR [0.1085] and SP [0.1087] patients [P > 0.99]. NAA/Cr and F in the NAWM were not correlated (r = 0.16, P > 0.7), mainly due to a lack of variation in F among patients. This may indicate a floor to the extent of myelin pathology that can occur in NAWM before a lesion appears, or that axonal damage is not strictly related to demyelination. The correlation between NAWM NAA/Cr and T2w lesion volume was not significant (P > 0.1). However, dividing the lesion volumes by the mean F in T2w lesions resulted in a quantity that correlated well with NAWM NAA/Cr (r = -0.78, P = 0.038), possibly reflecting the association of Wallerian degeneration in the NAWM with axonal transection associated with demyelination within lesions.

Purpose To use quantitative magnetization transfer imaging (qMTI) in an investigation of T1-weighted hypointensity observed in clinical magnetic resonance imaging (MRI) scans of multiple sclerosis (MS) patients, which has previously been proposed as a more specific indicator of tissue damage than the more commonly detected T2 hyperintensity. Materials and Methods A cross-sectional study of 10 MS patients was performed using qMTI. A total of 60 MTI measurements were collected in each patient at a resolution of 2 × 2 × 7 mm, over a range of saturation pulses. The observed T1 and T2 were also measured. qMT model parameters were estimated using a voxel-by-voxel fit. Results A total of 65 T2-hyperintense lesions were identified; 53 were also T1 hypointense. In these black holes, the qMTI-derived semisolid pool fraction F correlated negatively with T1,obs (r2 = 0.76; P < 0.0001). The water pool absolute size (PDf) showed a weaker correlation with T1,obs (positive, r2 = 0.53; P < 0.0001). The magnetization transfer ratio (MTR) showed a similarly strong correlation with F and a weaker correlation with PDf (r2 = 0.18; P < 0.04). Conclusion T1 increases in chronic black holes strongly correlated with the decline in semisolid pool size, and somewhat less to the confounding effect of edema. MTR was less sensitive than T1,obs to liquid pool changes associated with edema. J. Magn. Reson. Imaging 2005;21:103–110. © 2005 Wiley-Liss, Inc.

Objective:Hemangiopericytoma is an aggressive vascular tumour that rarely affects the central nervous system and is even more rarely spinal in presentation. The clinical features of a patient with a recurrent extraspinal hemangiopericytoma presenting with an epidural spinal cord compression by local invasion are described, including a review of the literature on metastatic hemangiopericytoma to the spine.Methods:A case of a 53-year-old male, with a recurrent extraspinal hemangiopericytoma which metastasized to the thoracic spine five years after detection of the primary tumour is presented. A chart review was conducted where all pertinent history, physical, laboratory, and radiological data were collected. A Pub-Med search using the keyword “hemangiopericytoma” identified all reported cases documenting clinical features, treatment, recurrence and outcome with respect to metastatic hemangiopericytoma to the spine.Results:Nine patients have been reported to have metastatic hemangiopericytoma to the spine. The median patient age was 47 years and there was a slight male preference. An unusual feature of the hemangiopericytoma is the prolonged period, up to 16 years, between the diagnosis of the primary hemangiopericytoma and the metastases to the spine. All patients were treated with a combination of radiation and surgery.Conclusion:Hemangiopericytomas show a slow clinical evolution with a strong propensity to relapse long after previous treatment and thus, once identified, prolonged follow-up for recurrence is indicated. A close follow-up of these patients is required because of frequent recurrences and delayed metastases even if the primary lesion was well-controlled. Although overall uncommon, hemangiopericytoma should be kept in mind in the differential diagnosis of vascular epidural spinal cord tumours.

A quantitative magnetization transfer imaging (qMTI) study, based on a two-pool model of magnetization transfer, was performed on seven normal subjects to determine, on a regional basis, normal values for the pool sizes, exchange, and relaxation parameters that characterize the MT phenomenon. Regions were identified on high-resolution anatomical scans using a combination of manual and automatic methods. Only voxels identified as pure tissue at the resolution of the quantitative scans were considered for analysis. While no left/right differences were observed, significant differences were found among white-matter regions and gray-matter regions. These regional differences were compared with existing cytoarchitectural data. In addition, the pattern and magnitude of the regional differences observed in white matter was found to be different from that reported previously for an alternative putative MRI measure of myelination, the 10-50-ms T2 component described as myelin water.

Autoimmune haemolysis or thrombocytopenia can complicate purine nucleoside monotherapy for chronic lymphocytic leukaemia (CLL), but Evans syndrome is rare. This is a report of the occurrence of pancytopenia secondary to a unique combination of red cell aplasia with autoimmune thrombocytopenia and neutropenia in a patient with CLL following treatment with fludarabine and cyclophosphamide. This case is unusual for the simultaneous targeting of three haemopoietic lineages by immune dysfunction following fludarabine and cyclophosphamide, which is a treatment regimen believed to reduce autoimmune haematological toxicity in CLL.

Smothering, when birds group together in a way that results in death from suffocation, is a welfare and economic concern for the egg industry. This questionnaire-based study explored correlations between disease, housing, management practices and smothering on free-range farms. A binomial logistic regression approach was used to test whether question responses predicted occurrence of nest box smothers (NBS) and panic and recurring smothers (PSRS) on farms. Breed (P=0.008) and nest box manufacturer (P=0.014) predicted NBS. Breed and nest box design have been previously reported to affect nesting behaviour. The affect of nest box manufacturer found in this study may illustrate the effect of nest box design features or house layouts. Nest box manufacturer (P=0.009), feeding oyster grit or grain on the litter (P

Although continuous positive airway pressure, oral appliances and surgical modifications of the airway are considered as part of the routine management of patients with obstructive sleep apnea, many new and unconventional therapies exist. Many of the trials using these new alternatives have been limited by insufficient data, poor trial design, small sample size, unclear inclusion criteria, lack of randomization, and lack of blinding, and on occasion are biased by retrospective design. Bariatric surgery, positional therapy, auto-titrating positive airway pressure, serotonin agents, wake promoting agents, genioglossus stimulation surgery, supplemental oxygen, nasal dilators, nasal expiratory resistor devices and oropharyngeal exercises will be reviewed. As obstructive sleep apnea impacts the individual and society at large, further research is needed to explore new therapeutic treatment options for obstructive sleep apnea. Therapeutic trials for obstructive sleep apnea must be of rigorous design to prove clinical effectiveness while taking into account both patient satisfaction and cost effectiveness.

Obstructive sleep apnea (OSA) affects millions of Americans and is estimated to be as prevalent as asthma and diabetes. Given the fact that obesity is a major risk factor for OSA, and given the current global rise in obesity, the prevalence of OSA will increase in the future. Individuals with sleep apnea are often unaware of their sleep disorder. It is usually first recognized as a problem by family members who witness the apneic episodes or is suspected by their primary care doctor because of the individual’s risk factors and symptoms. The vast majority remain undiagnosed and untreated, despite the fact that this serious disorder can have significant consequences. Individuals with untreated OSA can stop breathing hundreds of times a night during their sleep. These apneic events can lead to fragmented sleep that is of poor quality, as the brain arouses briefly in order for the body to resume breathing. Untreated, sleep apnea can have dire health consequences and can increase the risk of hypertension, diabetes, heart disease, and heart failure. OSA management has also become important in a number of comorbid neurological conditions, including epilepsy, stroke, multiple sclerosis, and headache. Diagnosis typically involves use of screening questionnaires, physical exam, and an overnight polysomnography or a portable home study. Treatment options include changes in lifestyle, positive airway pressure, surgery, and dental appliances.

A 25-year-old male presented to the sleep clinic with a chief complaint of excessive daytime somnolence and witnessed nocturnal “choking episodes” dating back a few years. His Epworth Sleepiness Scale score was 13. His usual bed time and rise time were 23:00 and 07:00, respectively. There was no history of snoring, and the patient denied a history of cataplexy, hypnopompic/hypnagogic hallucinations, or sleep paralysis. Six weeks prior to his sleep study, his primary care physician had prescribed paroxetine 20 mg daily, and 2 weeks prior to the study, trazodone 50 mg at bedtime had been added to his medication regimen. These medications were prescribed to treat depression with comorbid anxiety that had been present for many years but were not currently treated. In spite of a regular sleep schedule of 8 h per night, he often fell asleep on the job. The patient noted that his excessive daytime sleepiness predated the use of the antidepressants. His family history was positive for a father with obstructive sleep apnea. His physical examination revealed normal vital signs with a body mass index of 23.5. Head, ears, eyes, nose and throat examination were unremarkable, as was the cardiopulmonary examination. An overnight diagnostic polysomnogram (PSG) was obtained with the hypnogram shown in Figure 1 and a summary of pertinent results in Table 1. Figure 1 Hypnogram showing the summary of sleep stages for the sleep period. Note the large amount of REM sleep (as designated by R in the y axis) with the arrows pointing to these areas of interest. Table 1 Diagnostic Polysomnogram Summary of Sleep Time Statistics, Sleep Stage Statistics and Respiratory Event Statistics A multiple sleep latency test (MSLT) was ultimately obtained following the PSG to evaluate objectively his severity of somnolence (Table 2). Table 2 Results of the Multiple Sleep Latency Test Question: What additional information would be important to request from the patient to help explain the findings seen on the PSG and MSLT? Answer: A list of any medications or recreational drugs recently started or stopped. One may consider drug screening to ensure that the findings are not pharmacologically induced. Sleep logs for 1 week prior to the MSLT to assess prior sleep-wake schedules can sometimes be helpful to look for insufficient sleep.

Autoimmune haemolysis or thrombocytopenia can complicate purine nucleoside monotherapy for chronic lymphocytic leukaemia (CLL), but Evans syndrome is rare. This is a report of the occurrence of pancytopenia secondary to a unique combination of red cell aplasia with autoimmune thrombocytopenia and neutropenia in a patient with CLL following treatment with fludarabine and cyclophosphamide. This case is unusual for the simultaneous targeting of three haemopoietic lineages by immune dysfunction following fludarabine and cyclophosphamide, which is a treatment regimen believed to reduce autoimmune haematological toxicity in CLL.

Purpose of review To explore the role of iron physiology in the brain of healthy adults and review how increased brain iron deposition has been associated with common neurodegenerative diseases that affect the elderly. Recent findings Because iron plays a role in oxygen transportation, myelin synthesis, neurotransmitter production, and electron transfers, it serves as a crucial cofactor in normal central nervous metabolism. However, an increased level of brain iron may promote neurotoxicity due to free radical formation, lipid peroxidation, and ultimately, cellular death. Advanced neuroimaging techniques and pathological studies have demonstrated increased brain iron with aging, and increased iron deposition has also been observed in patients with a constellation of neurological diseases, including Alzheimer's disease, Parkinson's disease, and stroke. Summary Pathologic and neurologic imaging coupled with experimentation have increased our understanding of the link between iron and neurodegeneration. A potential implication is that disease-modifying therapies aimed at removing excess iron may one day be part of the armamentarium employed by clinicians to decrease the burden of neurodegenerative diseases in the elderly.

Acute demyelinating optic neuritis (ON) is a leading consideration in the differential diagnosis for young adults presenting with sudden onset of painful unilateral visual loss. Multiple sclerosis (MS) is believed to be the most common etiology for ON. Nearly 50% of MS patients will develop ON, and in 15-20% of cases, ON will be the initial manifestation of the illness. Conventional and emerging magnetic resonance imaging (MRI) techniques have provided greater insight into the pathophysiology of ON, and conventional MRI has also allowed clinicians to better estimate the future risk of MS. At 10 years after ON, patients with zero, one, or two or more brain lesions on T2-weighted MRI sequences demonstrated a 22%, 52%, and 56% risk of developing MS, respectively. Treatment with high dose intravenous methylprednisolone may accelerate visual recovery in patients with acute ON, but has little impact on long term visual outcome. Disease modifying therapies in patients with acute demyelinating ON should be considered as a treatment option at the time of initial presentation in those patients whose initial brain MRI shows demyelinating lesions as these therapies have been shown in to be effective at reducing the future risk of MS.

Deposition of iron in the brain is proposed to play a role in the pathophysiology of the normal aging process and neurodegenerative diseases. Whereas iron is required for normal neuronal metabolism, excessive levels can contribute to the formation of free radicals, leading to lipid peroxidation and neurotoxicity. Magnetic resonance imaging (MRI) is a powerful tool to detect excessive iron in the brain and longitudinally monitor changes in iron levels. Iron deposition is associated with a reduction in the T2 relaxation time, leading to hypointensity on spin-echo and gradient-echo T2-weighted images. The MRI changes associated with iron deposition have been observed both in normal aging and in various chronic neurological diseases, including multiple sclerosis, Alzheimer disease, and Parkinson disease. Magnetic resonance imaging metrics providing information about iron concentrations include R2, R2', and R2*. The purpose of this review is to discuss the role of iron and its detection by MRI in various neurological disorders. We will review the basic biochemical properties of iron and its influence on MRI signal. We will also summarize the sensitivity and specificity of MRI techniques in detecting iron. The MRI and pathological findings pertaining to brain iron will be reviewed with respect to normal aging and a variety of neurological disorders. Finally, the biochemistry and pathophysiology surrounding iron, oxidative stress, free radicals, and lipid peroxidation in the brain will be discussed, including therapeutic implications. The potential role of iron deposition and its assessment by MRI provides exciting potential applications to the diagnosis, longitudinal monitoring, and therapeutic development for disorders of the brain.

Background:The pathophysiological basis for differences in disability in patients with multiple sclerosis is unclear.Methods:We used magnetic resonance imaging to examine whether differences in disability in cohorts of multiple sclerosis patients with similar T2-weighted lesion volume and disease duration were associated with a more destructive disease process in the more disabled patients.Results:The benign and severely disabled groups had similar brain atrophy metrics and similar decreases of the neuronal marker, N-acetylaspartate, in the normal appearing white matter of the cerebrum on magnetic resonance spectroscopy examination in vivo. The severely disabled cohort had more spinal cord atrophy.Conclusion:The dissociation of spinal cord atrophy and cerebral atrophy between these two groups suggests that the difference between the more benign and more disabled groups cannot be explained by a more aggressive pathological process that is affecting the entire neuroaxis in a homogeneous fashion.

This study was undertaken to search for possible mechanisms by which T-cell lines become non-immunogenic and refractory to cellular-mediated lysis during culture. We demonstrate that mouse lymphoblasts (LB) lost their susceptibility to specific cytotoxic T lymphocyte (CTL)-mediated lysis following culture for more than 5 days in the presence interleukin-2 (IL-2), IL-7 but not IL-4. In contrast, the cultured lymphoblasts (CLB) were efficiently lysed by specific antibody and C' and by CTL in the presence of concanavalin A. In addition, CLB did not inhibit cytotoxicity against LB in a cold target competition assay, indicating that CLB and LB differ in the expression of certain surface molecules. Indeed, a significantly lower expression of H-2D class I antigen, the Fas antigen and the adhesion molecules intracelluar adhesion molecule-1 (ICAM-1) and very late activation antigen-4 (VLA-4) was observed on the CLB surface. Consequently, CLB could not form conjugates with specific CTL, a prerequisite for CTL-mediated lysis. In addition, there was a marked decrease in CLB immunogenicity: the cultured cells were unable to stimulate allogeneic spleen cells in mixed lymphocyte culture nor could they induce a cytotoxic response following their injection into allogeneic mice. The reduced immunogenicity enabled the prolonged survival of active CLB in an allogeneic host. We suggest that the extended survival in an allogeneic tumour-bearing host of cultured, hence weakly immunogenic, anti-tumour CTL, will enable them the in vivo implementation of their anti-tumour activity.

In a retrospective multicenter study 28 relapse fractures of the forearm in children were reviewed. The male to female ratio was 23:5. Six children were younger than 6 years, 12 were between 6 and 10 years, and 10 were between 10 and 14 years old. The primary fracture was treated by cast fixation of 3-7 weeks duration. The refracture occurred on a average 14 weeks (4-32 weeks) after the primary fracture by a simple fall (n = 14) or a fall from height (n = 4), or during school (n = 6) or leisure-time (n = 3) sporting activities. In 84% of the patients partial consolidation, i.e. incomplete healing of one cortex of one or both forearm bones, preceded the refracture. In the majority of patients this was observed after a green stick fracture due to permanent angulation. Six patients were operated upon for irreducibility of the relapse fracture; the others were treated by conservative means. In two patients a second refracture occurred. Fifteen patients were available for a 2 year result. Definitive angulation of more than 10 degrees caused a clinically relevant limitation of pro-supination in five of six patients. To prevent relapse fractures of the forearm in children, complete circular consolidation of the original fracture has to be guaranteed. It remains unclear whether this is best achieved by special plaster techniques or by converting a greenstick fracture into a complete, unstable fracture.

We present a simple, cost-effective method for creating diffractive optical elements on the surfaces of optical fibers and fiber-optic components by use of 193-nm ablation techniques. It is an outgrowth of a more fundamental investigation of the effects of intense UV radiation fields on SiO2- and Ge–SiO2-based structures (specifically optical fibers and preforms) and allows the inexpensive fabrication of structures such as the suggested evanescent-field-based sensing device.

PRECISE control is essential to the successful operation of any commercial process, particularly of those processes involving the use of rubber latex. Latex is, of course, a complex natural product; it contains a variety of nonrubber constituents, such as proteins, soaps, and others which control or influence its colloidal properties. In order to ensure uniform behavior of latex in process, it is obviously desirable to test its uniformity as a raw product. It is furthermore important that such tests should be, wherever possible, fundamentally sound and free from the personal equation. Unless the results can be expressed in basic fundamental units, which are independent of the apparatus used and of the operator, confusion will result. It is the purpose of this paper to review critically the more important general physical tests and methods of analysis which can be applied to latex, particularly from the standpoint of accuracy and sources of error, and to recommend certain procedures on the basis of commercial experience in the authors' control laboratories. Some of the recommended methods have been developed in these laboratories, while others have been improved over procedures given in earlier works on latex (3, 6, 9). Part I is concerned with physical tests such as pH, surface tension, viscosity, and mechanical stability, while Part II is concerned with analytical methods.

The presence of fine eoagulum in latex affects some processes very adversely. This coagulum is often wrongly blamed on some complicated chemical or physical action in the compound when the true explanation is that all the larger particles were present in the original latex or dispersions from which the compound was made. The latex strainability test measures the amount of latex that will pass through a filter medium before clogging.