Search

We are reporting a unique case of drosophila larva nasal myiasis (NM) in a 72-year-old male patient admitted to the ICU with diffuse muscle weakness and respiratory failure due to myasthenia gravis crisis and septic shock due to pseudomonas pneumonia. The myiasis was noticed on the third day of admission two days following traumatic insertion of a nasogastric tube. The patient underwent nasal endoscopic mechanical extraction and lidocaine nasal spray with saline nasal flushes. To our knowledge, this is the first case report of NM in a myasthenia gravis (MG) patient. Chronic muscle weakness in MG patients might play a role in having NM as these patients are less likely to be able to protect themselves from flies. Managing NM in our patient was challenging due to the potential neurologic side effects of most of treatment options mentioned in the literature.

Isolated basilar artery stenosis (BAS) is a rare etiology of ischemic neurologic conditions. First-line treatment of symptomatic stenosis is typically medical therapy as outlined in the Warfarin–Aspirin Symptomatic Intracranial Disease (WASID) trial and the Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial.1,2 We present the case of a male in his 60s with isolated BAS who failed maximal medical treatment but experienced a decrease in transient ischemic attacks and acute ischemic stroke occurrences after angioplasty and stenting.

Background.Long, slow haemodialysis (24 h/week) has been associated with excellent patient survival and reduced cardiovascular mortality. Comparisons of patient survival have only been possible with registry data and other published series which do not control for individual patient characteristics. This retrospective study compares actuarial patient survival between a unit using long, slow haemodialysis (Tassin) and one employing 'conventional' haemodialysis (Nottingham). [ABSTRACT FROM PUBLISHER]

Serum and urinary urate concentrations were studied in 44 patients with homozygous sickle cell (SS) disease, and in 27 controls with normal haemoglobin. Hyperuricaemia (>0·39 mmol/l (6·5 mg/100 ml)) occurred in 41% of SS patients and inversely correlated with renal urate clearance but not with indices of bone marrow turnover. Higher serum urate concentrations occurred in patients with proteinuria, probably due to associated tubular damage. Higher serum urate concentrations and lower urate clearance occurred in males compared to females. [ABSTRACT FROM PUBLISHER]

Background:  With the growing relevance of artificial intelligence (AI)-based patient-facing information, microsurgical-specific online information provided by professional organizations was compared with that of ChatGPT (Chat Generative Pre-Trained Transformer) and assessed for accuracy, comprehensiveness, clarity, and readability., Methods:  Six plastic and reconstructive surgeons blindly assessed responses to 10 microsurgery-related medical questions written either by the American Society of Reconstructive Microsurgery (ASRM) or ChatGPT based on accuracy, comprehensiveness, and clarity. Surgeons were asked to choose which source provided the overall highest-quality microsurgical patient-facing information. Additionally, 30 individuals with no medical background (ages: 18-81, μ = 49.8) were asked to determine a preference when blindly comparing materials. Readability scores were calculated, and all numerical scores were analyzed using the following six reliability formulas: Flesch-Kincaid Grade Level, Flesch-Kincaid Readability Ease, Gunning Fog Index, Simple Measure of Gobbledygook Index, Coleman-Liau Index, Linsear Write Formula, and Automated Readability Index. Statistical analysis of microsurgical-specific online sources was conducted utilizing paired t -tests., Results:  Statistically significant differences in comprehensiveness and clarity were seen in favor of ChatGPT. Surgeons, 70.7% of the time, blindly choose ChatGPT as the source that overall provided the highest-quality microsurgical patient-facing information. Nonmedical individuals 55.9% of the time selected AI-generated microsurgical materials as well. Neither ChatGPT nor ASRM-generated materials were found to contain inaccuracies. Readability scores for both ChatGPT and ASRM materials were found to exceed recommended levels for patient proficiency across six readability formulas, with AI-based material scored as more complex., Conclusion:  AI-generated patient-facing materials were preferred by surgeons in terms of comprehensiveness and clarity when blindly compared with online material provided by ASRM. Studied AI-generated material was not found to contain inaccuracies. Additionally, surgeons and nonmedical individuals consistently indicated an overall preference for AI-generated material. A readability analysis suggested that both materials sourced from ChatGPT and ASRM surpassed recommended reading levels across six readability scores., Competing Interests: None declared., (Thieme. All rights reserved.)

Abstract: The number of cancer survivors continues to increase because of advances in therapeutic modalities. Along with surgery and chemotherapy, radiotherapy is a commonly used treatment modality in roughly half of all cancer patients. It is particularly helpful in the oncologic treatment of patients with breast, head and neck, and prostate malignancies. Unfortunately, among patients receiving radiation therapy, long-term sequalae are often unavoidable, and there is accumulating clinical evidence suggesting significant radiation-related damage to the vascular endothelium. Ionizing radiation has been known to cause obliterative fibrosis and increased wall thickness in irradiated blood vessels. Clinically, these vascular changes induced by ionizing radiation can pose unique surgical challenges when operating in radiated fields. Here, we review the relevant literature on radiation-induced vascular damage focusing on mechanisms and signaling pathways involved and highlight microsurgical anastomotic outcomes after radiotherapy. In addition, we briefly comment on potential therapeutic strategies, which may have the ability to mitigate radiation injury to the vascular endothelium., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Cancer is currently the second leading cause of death in the United States. There is increasing evidence that the tumor microenvironment (TME) is pivotal for tumorigenesis and metastasis. Recently, adipocytes and cancer-associated fibroblasts (CAFs) in the TME have been shown to play a major role in tumorigenesis of different cancers, specifically melanoma. Animal studies have shown that CAFs and adipocytes within the TME help tumors evade the immune system, for example, by releasing chemokines to blunt the effectiveness of the host defense. Although studies have identified that adipocytes and CAFs play a role in tumorigenesis, adipocyte transition to fibroblast within the TME is fairly unknown. This review intends to elucidate the potential that adipocytes may have to transition to fibroblasts and, as part of the TME, a critical role that CAFs may play in affecting the growth and invasion of tumor cells. Future studies that illuminate the function of adipocytes and CAFs in the TME may pave way for new antitumor therapies., Competing Interests: Conflicts of interest and sources of funding: none declared. This work was supported by the Hagey Laboratory for Pediatric Regenerative Medicine., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

In the Dobbs decision the United States Supreme Court overturned Roe v. Wade, returning the issue of abortion to the states. To date, there is little published data on the impact this might have on where future residents choose to pursue graduate medical education. We investigated the potential effects of the resultant varied political landscape of abortion care access laws with respect to influence on the selection of prospective diagnostic radiology training programs by medical students, comparing application rates for the 2022 recruitment cycle to the prior 4 years across a geographically diverse group of 22 academic and community sites across the United States. We provide strategies for program directors to consider in dealing with topics related to this continually evolving issue as it pertains to resident recruitment and retention., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Cerebrovascular reactivity (CVR) is inversely related to white matter hyperintensity severity, a marker of cerebral small vessel disease (SVD). Less is known about the relationship between CVR and other SVD imaging features or cognition. We aimed to investigate these cross-sectional relationships., Methods: Between 2018 and 2021 in Edinburgh, we recruited patients presenting with lacunar or cortical ischemic stroke, whom we characterized for SVD features. We measured CVR in subcortical gray matter, normal-appearing white matter, and white matter hyperintensity using 3T magnetic resonance imaging. We assessed cognition using Montreal Cognitive Assessment. Statistical analyses included linear regression models with CVR as outcome, adjusted for age, sex, and vascular risk factors. We reported regression coefficients with 95% CIs., Results: Of 208 patients, 182 had processable CVR data sets (median age, 68.2 years; 68% men). Although the strength of association depended on tissue type, lower CVR in normal-appearing tissues and white matter hyperintensity was associated with larger white matter hyperintensity volume (B NAWM =-0.0073 [95% CI, -0.0133 to -0.0014] %/mm Hg per 10-fold increase in percentage intracranial volume), more lacunes (B NAWM =-0.00129 [95% CI, -0.00215 to -0.00043] %/mm Hg per lacune), more microbleeds (B NAWM =-0.00083 [95% CI, -0.00130 to -0.00036] %/mm Hg per microbleed), higher deep atrophy score (B NAWM =-0.00218 [95% CI, -0.00417 to -0.00020] %/mm Hg per score point increase), higher perivascular space score (B NAWM =-0.0034 [95% CI, -0.0066 to -0.0002] %/mm Hg per score point increase in basal ganglia), and higher SVD score (B NAWM =-0.0048 [95% CI, -0.0075 to -0.0021] %/mm Hg per score point increase). Lower CVR in normal-appearing tissues was related to lower Montreal Cognitive Assessment without reaching convention statistical significance (B NAWM =0.00065 [95% CI, -0.00007 to 0.00137] %/mm Hg per score point increase)., Conclusions: Lower CVR in patients with SVD was related to more severe SVD burden and worse cognition in this cross-sectional analysis. Longitudinal analysis will help determine whether lower CVR predicts worsening SVD severity or vice versa., Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN12113543., Competing Interests: Disclosures Drs Morgan and Stringer receive funding from Siemens Healthineers. The other authors report no conflicts.

Introduction: While 2D phase-contrast MRI is often used to examine intracranial vessels in neurovascular disease contexts, the ability of 4D flow to assess many vessels at once makes it an attractive alternative. We aimed to assess the repeatability, reliability, and conformity of 2D and 4D flow across intracranial vessels., Methods: Using correlation analyses and paired t -tests, test-retest repeatability, intra-rater reliability, and inter-method conformity for measurements of pulsatility index (PI) and mean flow were assessed in the arteries and veins of 11 healthy volunteers. Inter-method conformity was also assessed in 10 patients with small vessel disease., Results: Repeatability for PI measurements was mostly classed as good using both 2D (median ICC = 0.765) and 4D (0.772) methods, and for mean flow was mostly moderate across both (2D: 0.711, 4D: 0.571). 4D reliability was good for PI (0.877-0.906) and moderate for mean flow (0.459-0.723). Arterial PI measurements were generally higher using the 2D method, while mean flow was mostly higher using 4D flow., Discussion: These results imply that PI measurement using 4D flow is repeatable and reliable across intracranial arteries and veins, but care should be paid to absolute flow measurements as they are susceptible to variation depending on slice placement, resolution, and lumen segmentation practices., Competing Interests: NJ was employed by Siemens Medical Solutions USA, Inc. The authors declare that this study received funding from Siemens Healthcare, which had the following involvement in the study: provision of work-in-progress 4D flow MRI pulse sequence; NJ reviewed the draft manuscript for technical accuracy. While AM’s PhD was partially funded by Siemens, all research was carried out without commercial influence. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Morgan, Thrippleton, Stringer, Jin, Wardlaw and Marshall.)

Wound healing results in the formation of scar tissue which can be associated with functional impairment, psychological stress, and significant socioeconomic cost which exceeds 20 billion dollars annually in the United States alone. Pathologic scarring is often associated with exaggerated action of fibroblasts and subsequent excessive accumulation of extracellular matrix proteins which results in fibrotic thickening of the dermis. In skin wounds, fibroblasts transition to myofibroblasts which contract the wound and contribute to remodeling of the extracellular matrix. Mechanical stress on wounds has long been clinically observed to result in increased pathologic scar formation, and studies over the past decade have begun to uncover the cellular mechanisms that underly this phenomenon. In this article, we will review the investigations which have identified proteins involved in mechano-sensing, such as focal adhesion kinase, as well as other important pathway components that relay the transcriptional effects of mechanical forces, such as RhoA/ROCK, the hippo pathway, YAP/TAZ, and Piezo1. Additionally, we will discuss findings in animal models which show the inhibition of these pathways to promote wound healing, reduce contracture, mitigate scar formation, and restore normal extracellular matrix architecture. Recent advances in single cell RNA sequencing and spatial transcriptomics and the resulting ability to further characterize mechanoresponsive fibroblast subpopulations and the genes that define them will be summarized. Given the importance of mechanical signaling in scar formation, several clinical treatments focused on reducing tension on the wound have been developed and are described here. Finally, we will look toward future research which may reveal novel cellular pathways and deepen our understanding of the pathogenesis of pathologic scarring. The past decade of scientific inquiry has drawn many lines connecting these cellular mechanisms that may lead to a map for the development of transitional treatments for patients on the path to scarless healing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Berry, Downer, Morgan, Griffin, Liang, Kameni, Laufey Parker, Guo, Longaker and Wan.)

Handwritten documents may contain probative DNA, but most crime laboratories do not process this evidence. DNA recovery should not impair other evidence processing such as latent prints or indented writing. In this study, single fingermarks on paper were sampled with flocked swabs, cutting, and dry vacuuming. In addition, two extraction methods were compared for the sample type. DNA yields were low across all methods; however, this work confirms the ability to recover DNA from paper and the usefulness of the vacuum sampling method combined with the Chelex-Tween method. Stability of touch DNA deposits were compared over an 11-month period to better understand degradation that may occur over time. No significant difference in DNA recovery was observed, suggesting DNA deposits on paper are stable over an 11-month span.

Competing Interests: The authors declare no conflicts of interest.

Competing Interests: The authors declare no conflicts of interest.

Background: Cerebral small vessel disease is a major cause of dementia and stroke, visible on brain magnetic resonance imaging. Recent data suggest that small vessel disease lesions may be dynamic, damage extends into normal-appearing brain and microvascular dysfunctions include abnormal blood-brain barrier leakage, vasoreactivity and pulsatility, but much remains unknown regarding underlying pathophysiology, symptoms, clinical features and risk factors of small vessel disease. Patients and Methods: The Mild Stroke Study 3 is a prospective observational cohort study to identify risk factors for and clinical implications of small vessel disease progression and regression among up to 300 adults with non-disabling stroke. We perform detailed serial clinical, cognitive, lifestyle, physiological, retinal and brain magnetic resonance imaging assessments over one year; we assess cerebrovascular reactivity, blood flow, pulsatility and blood-brain barrier leakage on magnetic resonance imaging at baseline; we follow up to four years by post and phone. The study is registered ISRCTN 12113543., Summary: Factors which influence direction and rate of change of small vessel disease lesions are poorly understood. We investigate the role of small vessel dysfunction using advanced serial neuroimaging in a deeply phenotyped cohort to increase understanding of the natural history of small vessel disease, identify those at highest risk of early disease progression or regression and uncover novel targets for small vessel disease prevention and therapy., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: UC, MS, MJT, GB, AM, OH, CM, FND and JMW hold academic grants from government and charitable funding agencies, outlined below., (© European Stroke Organisation 2020.)

The brain's vasculature is essential for brain health and its dysfunction contributes to the onset and development of many dementias and neurological disorders. While numerous in vivo imaging techniques exist to investigate cerebral haemodynamics in humans, phase-contrast magnetic resonance imaging (MRI) has emerged as a reliable, non-invasive method of quantifying blood flow within intracranial vessels. In recent years, an advanced form of this method, known as 4D flow, has been developed and utilised in patient studies, where its ability to capture complex blood flow dynamics within any major vessel across the acquired volume has proved effective in collecting large amounts of information in a single scan. While extremely promising as a method of examining the vascular system's role in brain-related diseases, the collection of 4D data can be time-consuming, meaning data quality has to be traded off against the acquisition time. Here, we review the available literature to examine 4D flow's capabilities in assessing physiological and pathological features of the cerebrovascular system. Emerging techniques such as dynamic velocity-encoding and advanced undersampling methods, combined with increasingly high-field MRI scanners, are likely to bring 4D flow to the forefront of cerebrovascular imaging studies in the years to come.

Background and Purpose- Perivascular spaces (PVS) around venules may help drain interstitial fluid from the brain. We examined relationships between suspected venules and PVS visible on brain magnetic resonance imaging. Methods- We developed a visual venular quantification method to examine the spatial relationship between venules and PVS. We recruited patients with lacunar stroke or minor nondisabling ischemic stroke and performed brain magnetic resonance imaging and retinal imaging. We quantified venules on gradient echo or susceptibility-weighted imaging and PVS on T2-weighted magnetic resonance imaging in the centrum semiovale and then determined overlap between venules and PVS. We assessed associations between venular count and patient demographic characteristics, vascular risk factors, small vessel disease features, retinal vessels, and venous sinus pulsatility. Results- Among 67 patients (69% men, 69.0±9.8 years), only 4.6% (range, 0%-18%) of venules overlapped with PVS. Total venular count increased with total centrum semiovale PVS count in 55 patients after accounting for venule-PVS overlap (β=0.468 [95% CI, 0.187-0.750]) and transverse sinus pulsatility (β=0.547 [95% CI, 0.309-0.786]) and adjusting for age, sex, and systolic blood pressure. Conclusions- Despite increases in both visible PVS and suspected venules, we found minimal spatial overlap between them in patients with sporadic small vessel disease, suggesting that most magnetic resonance imaging-visible centrum semiovale PVS are periarteriolar rather than perivenular.

Edaravone is considered to be a potent antioxidant drug known to scavenge free radical species and prevent free radical-induced lipid peroxidation. In this study, we investigated the effect of edaravone on the myeloperoxidase (MPO) activity, an enzyme responsible for the production of an array of neutrophil-derived oxidants that can cause cellular damage. The addition of edaravone to the reaction of MPO and hydrogen peroxide (H 2 O 2 ) significantly enhanced the reduction of MPO Compound II back to native MPO. Interestingly, the MPO-mediated production of toxic hypochlorous acid exhibited a concentration-dependent biphasic effect, with the apparent optimal edaravone concentration at 10 μM. Oxidation of edaravone by MPO was examined by various analytical methods. An MPO-catalyzed product(s) of edaravone was identified at 350 nm by kinetic analysis of UV-Vis spectroscopy. Several MPO-catalyzed metabolites of edaravone were proposed from the LC-MS analyses, including oxidized dimers from edaravone radicals. Electron spin resonance (ESR) spin trapping detected a carbon-centred radical metabolite of edaravone. NMR studies revealed that there are two exchangeable hydrogens, one of which is on the α-carbon, justifying the carbon-centred edaravone radical produced from MPO. Despite the formation of an edaravone carbon-radical metabolite, it did not appear to effectively oxidize GSH (in comparison with phenoxyl radicals). Viability (ATP) and cytotoxicity (LDH release) assays showed a concentration-dependent effect of edaravone on HL-60 cells treated with either a bolus concentration of 30 μM H 2 O 2 or a flux of H 2 O 2 generated by 5 mM glucose and 10 mU/mL glucose oxidase. The H 2 O 2 -induced toxicity was ameliorated at high edaravone concentrations (100-200 μM). In contrast, low concentrations of edaravone (1-10 μM) exacerbated the H 2 O 2 -induced toxicity. However, the effect of edaravone at low concentration (0-10 μM) appeared more prominent with the LDH assay only. The cellular findings correlated with the biochemical studies with respect to hypochlorous acid formation. These findings provide interesting perspectives regarding the duality of edaravone as an antioxidant drug., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: In patients who undergo surgery for oropharyngeal masses, intubation is almost always successful. However, technical aspects of airway management, including bag mask ventilation and oxygenation, may still be difficult. Although rates of airway difficulty and intubation success in these patients have been studied, these data may not reflect difficulty with individual components of the intubation process. We hypothesized that rates of complications with individual elements of the intubation process would not be reflected in the rate of eventual intubation success. To test our hypothesis, we observed the process of airway management and resulting complications with oxygenation and bag mask ventilation in patients with oropharyngeal masses undergoing otorhinolaryngology procedures under general anesthesia., Methods: Forty-four patients with oropharyngeal masses scheduled for surgery were observed during the process of airway management. Observers recorded the number of airway devices used, the overall number of intubation attempts, the number and type of manual maneuvers required during bag mask ventilation, and the incidence of oxygen desaturation. The eventual intubation success rate was also recorded., Results: All 44 patients (100%; 95% CI, 92%-100%) were successfully intubated. Thirty-six (81.8%) of 44 patients were intubated asleep and 8 (18.2%) of 44 were intubated awake using flexible fiberoptic bronchoscopy. Thirty-one (86.1%) of 36 patients who were intubated asleep received bag mask ventilation before intubation, while the other 5 patients underwent a rapid sequence induction. Twenty-seven (61.4%) of 44 patients (95% CI, 45%-75%) had ≥1 complication during airway management. Ten (23%) of 44 patients (95% CI, 11%-37%) required ≥3 attempts to intubate, 21 (68%) of 31 patients (95% CI, 49%-83%) had difficult mask ventilation, and 15 patients (34%; 95% CI, 20%-50%) experienced desaturation (oxygen saturation measured by pulse oximetry, <95%)., Conclusions: We found that, although all patients were successfully intubated, clinicians frequently encountered complications with both intubation and mask ventilation. These complications required frequent use of additional manual maneuvers during mask ventilation and a high incidence of oxygen desaturation. The difficulty of airway management in patients with oropharyngeal masses may not be effectively assessed by success rate alone.

The formation of isonicotinyl-nicotinamide adenine dinucleotide (INH-NAD + ) by the mycobacterial catalase-peroxidase enzyme, KatG, was known to be the major component of the mode of action of isoniazid (INH), an anti-tuberculosis drug. However, there are other enzymes that may catalyze this reaction. We have previously reported that neutrophil myeloperoxidase (MPO) is capable of metabolizing INH through the formation of INH-NAD + adduct, which could be attributed to being a possible mode of action of INH. However, eosinophilic infiltration of the lungs is more pronounced and characteristic of granulomas in Mycobacterium tuberculosis-infected patients. Thus, the aim of the present study is to investigate the role of eosinophil peroxidase (EPO), a key eosinophil enzyme, during INH metabolism and the formation of its active metabolite, INH-NAD + using purified EPO and eosinophils isolated from asthmatic donors. UV-Vis spectroscopy revealed INH oxidation by EPO led to a new product (λ max  = 326 nm) in the presence of NAD + . This adduct was confirmed to be INH-NAD + using LC-MS analysis where the intact adduct was detected (m/z = 769). Furthermore, EPO catalyzed the oxidation of INH and formed several free radical intermediates as assessed by electron paramagnetic resonance (EPR) spin-trapping; a carbon-centred radical, which is considered to be the reactive metabolite that binds with NAD + , was found when superoxide dismutase was included in the reaction. Our findings suggest that eosinophilic EPO may also play a role in the pharmacological activity of INH through the formation of INH-NAD + adduct, and supports further evidence that human cells and enzymes are capable of producing the active metabolite involved in tuberculosis treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Isoniazid (INH) is one of the oldest drugs for the treatment of tuberculosis (TB) and is of continual clinical and research interest. The aim of the current study is to investigate the ability of INH to induce monocyte differentiation and the underlying signaling pathway involved in this phenomenon using HL-60 cells. In this study, HL-60 cells were treated with different non-cytotoxic concentrations of INH or vitamin D (a well-known inducer of monocytic differentiation) to determine key functional changes in the phenotype of these cells using several biochemical and cytobiological experiments. HL-60 cells are derived from human promyelocytic leukemia and bear some resemblance to promyelocytes, which differentiate into various cell types. INH-induced differentiation was confirmed to occur in a concentration-dependent manner through several functional markers such as nonspecific esterase activity, NADPH oxidase activity and expression of surface markers CD14 and CD16 (characteristic of monocytes). INH-induced monocytic-like differentiation in HL-60 cells and demonstrated that at least 25% of cells were differentiated within the range of the pharmacological concentrations of INH. To determine the effects of INH on HL-60 cells, we applied quantitative proteomics that revealed 32 proteins were altered significantly in pathways that could involve differentiation signals. Lastly, INH activated the ERK-1/MAPK signaling pathway based on detection of phosphorylated ERK-1. These in vitro findings in HL-60 cells warrant further study using promyelocytes or hematopoietic stem cells to evaluate the physiological capability of INH to induce monocytic differentiation that may aid in host defense against TB., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The purpose of this study was to extend the concept of weighted CT dose index ([Formula: see text]) to the elliptical phantoms. Based on the published body dimension data, eight body aspect ratios were chosen between 1 (perfectly circular) and 1.72 (extremely elliptical). For each aspect ratio, two elliptical cylinders were created digitally to represent adult and pediatric bodies. Their cross-sectional areas were identical to the standard 32- and 16-cm CTDI phantoms. For each phantom, [Formula: see text] at center and periphery were simulated for tube voltages between 70 and 140 kVp using a validated Monte Carlo program. The simulations also provided the average dose over the cross-sectional area, [Formula: see text]. Values of [Formula: see text] and [Formula: see text] allowed linear systems of equations to be established, from which central and peripheral weighting coefficients were solved. Regardless of phantom shape, only two weighting coefficients were needed: [Formula: see text] for the central [Formula: see text] and [Formula: see text] for the average of the four peripheral [Formula: see text]'s. Over the full range of aspect ratios, [Formula: see text] increased linearly from 0.37 to 0.46, whereas [Formula: see text] decreased linearly from 0.63 to 0.54, allowing the concept of [Formula: see text] to be readily extended to the elliptical phantoms. When cross-sectional area (hence volume) was kept constant, all phantoms had the same [Formula: see text] regardless of shape.

In Monte Carlo simulation of CT dose, many input parameters are required (e.g. bowtie filter properties and scan start/end location). Our goal was to examine the uncertainties in patient dose when input parameters were inaccurate. Using a validated Monte Carlo program, organ dose from a chest CT scan was simulated for an average-size female phantom using a reference set of input parameter values (treated as the truth). Additional simulations were performed in which errors were purposely introduced into the input parameter values. The effects on four dose quantities were analyzed: organ dose (mGy/mAs), effective dose (mSv/mAs), CTDI vol -normalized organ dose (unitless), and DLP-normalized effective dose (mSv/mGy · cm). At 120 kVp, when spectral half value layer deviated from its true value by  ±1.0 mm Al, the four dose quantities had errors of 18%, 7%, 14% and 2%, respectively. None of the dose quantities were affected significantly by errors in photon path length through the graphite section of the bowtie filter; path length error as large as 5 mm produced dose errors of  ⩽2%. In contrast, error of this magnitude in the aluminum section produced dose errors of  ⩽14%. At a total collimation of 38.4 mm, when radiation beam width deviated from its true value by  ±  3 mm, dose errors were  ⩽7%. Errors in tube starting angle had little impact on effective dose (errors  ⩽  1%); however, they produced organ dose errors as high as 66%. When the assumed scan length was longer by 4 cm than the truth, organ dose errors were up to 137%. The corresponding error was 24% for effective dose, but only 3% for DLP-normalized effective dose. Lastly, when the scan isocenter deviated from the patient's anatomical center by 5 cm, organ and effective dose errors were up 18% and 8%, respectively.

Background: Dental anxiety is common among children. Although there is a wealth of research investigating childhood dental anxiety, little consideration has been given to the child's perspective., Aim: This qualitative study sought to explore with children their own experiences of dental anxiety using a cognitive behavioural therapy assessment model., Design: Face-to-face, semi-structured interviews were conducted with dentally anxious children aged 11-16 years. The Five Areas model was used to inform the topic guide and analysis. Data were analysed using a framework approach., Results: In total, 13 children were interviewed. Participants described their experiences of dental anxiety across multiple dimensions (situational factors and altered thoughts, feelings, physical symptoms, and behaviours). Participants placed considerable value on communication by dental professionals, with poor communication having a negative influence on dental anxiety and the dentist-patient relationship., Conclusions: This study confirms the Five Areas model as an applicable theoretical model for the assessment of childhood dental anxiety. Children provided insights about their own dental anxiety experiences that have not previously been described., (© 2016 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Millions of people worldwide suffer from diseases that lead to paralysis through disruption of signal pathways between the brain and the muscles. Neuroprosthetic devices are designed to restore lost function and could be used to form an electronic 'neural bypass' to circumvent disconnected pathways in the nervous system. It has previously been shown that intracortically recorded signals can be decoded to extract information related to motion, allowing non-human primates and paralysed humans to control computers and robotic arms through imagined movements. In non-human primates, these types of signal have also been used to drive activation of chemically paralysed arm muscles. Here we show that intracortically recorded signals can be linked in real-time to muscle activation to restore movement in a paralysed human. We used a chronically implanted intracortical microelectrode array to record multiunit activity from the motor cortex in a study participant with quadriplegia from cervical spinal cord injury. We applied machine-learning algorithms to decode the neuronal activity and control activation of the participant's forearm muscles through a custom-built high-resolution neuromuscular electrical stimulation system. The system provided isolated finger movements and the participant achieved continuous cortical control of six different wrist and hand motions. Furthermore, he was able to use the system to complete functional tasks relevant to daily living. Clinical assessment showed that, when using the system, his motor impairment improved from the fifth to the sixth cervical (C5-C6) to the seventh cervical to first thoracic (C7-T1) level unilaterally, conferring on him the critical abilities to grasp, manipulate, and release objects. This is the first demonstration to our knowledge of successful control of muscle activation using intracortically recorded signals in a paralysed human. These results have significant implications in advancing neuroprosthetic technology for people worldwide living with the effects of paralysis.

The formation of isonicotinyl-nicotinamide adenine dinucleotide (INH-NAD(+)) via the mycobacterial catalase-peroxidase enzyme, KatG, has been described as the major component of the mode of action of isoniazid (INH). However, there are numerous human peroxidases that may catalyze this reaction. The role of neutrophil myeloperoxidase (MPO) in INH-NAD(+) adduct formation has never been explored; this is important, as neutrophils are recruited at the site of tuberculosis infection (granuloma) through infected macrophages' cell death signals. In our studies, we showed that neutrophil MPO is capable of INH metabolism using electron paramagnetic resonance (EPR) spin-trapping and UV-Vis spectroscopy. MPO or activated human neutrophils (by phorbol myristate acetate) catalyzed the oxidation of INH and formed several free radical intermediates; the inclusion of superoxide dismutase revealed a carbon-centered radical which is considered to be the reactive metabolite that binds with NAD(+). Other human metabolites, including N-acetyl-INH, N-acetylhydrazine, and hydrazine did not show formation of carbon-centered radicals, and either produced no detectable free radicals, N-centered free radicals, or superoxide, respectively. A comparison of these free radical products indicated that only the carbon-centered radical from INH is reducing in nature, based on UV-Vis measurement of nitroblue tetrazolium reduction. Furthermore, only INH oxidation by MPO led to a new product (λmax=326nm) in the presence of NAD(+). This adduct was confirmed to be isonicotinyl-NAD(+) using LC-MS analysis where the intact adduct was detected (m/z=769). The findings of this study suggest that neutrophil MPO may also play a role in INH pharmacological activity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

To combat tuberculosis (TB), host phagocytic cells need to survive against self-generating oxidative stress-induced necrosis. However, the effect of isoniazid (INH) in protecting cells from oxidative stress-induced necrosis has not been previously investigated. In this in vitro study, the cytotoxic effect of H2O2 generation using glucose oxidase (a model of oxidative stress) was found to be abrogated by INH in a concentration-dependent manner in HL-60 cells (a human promyelocytic leukemia cell). In cells treated with glucose oxidase, both ATP and mitochondrial membrane potential were found to be decreased. However, treatment with INH demonstrated small but significant attenuation in decreasing ATP levels, and complete reversal for the decrease in mitochondrial membrane potential. Quantitative proteomics analysis identified up-regulation of 15 proteins and down-regulation of 14 proteins which all together suggest that these proteomic changes signal for increasing cellular replication, structural integrity, ATP synthesis, and inhibiting cell death. In addition, studies demonstrated that myeloperoxidase (MPO) was involved in catalyzing INH-protein adduct formation. Unexpectedly, these covalent protein adducts were correlated with INH-induced cytoprotection in HL-60 cells. Further studies are needed to determine whether the INH-protein adducts were causative in the mechanism of cytoprotection., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Part 2 of this series of two articles addresses the Hall Technique for preformed metal crowns. It will discuss the need for an effective child and dentist friendly method to restore carious primary molars. The technique is described in detail and the evidence for its effectiveness and acceptance by children, parents, dentists and dental educators is presented. CPD/Clinical Relevance: Dentists and dental care professionals should be aware of the evidence to support the adoption of the Hall Technique.

Purpose: In CT imaging, a desirable quality assurance dose quantity should account for the dose variability across scan parameters and scanner models. Recently, AAPM Task Group 111 proposed to use equilibrium dose-pitch product (Dˆeq), in place of CT dose index (CTDI100), for scan modes involving table translation. The purpose of this work is to investigate whether this new concept better accounts for the tube voltage (kVp) dependence of organ dose than the conventional CTDI100., Methods: Three extended cardiac-torso patient models were included in this study. They represented normal-weight, overweight, and obese patients with abdomen-pelvis diameters ranging between 23 and 36 cm and body mass indices ranging between 20 and 42. A Monte Carlo program developed and validated for a 128-slice CT system was used to simulate organ dose for abdomen-pelvis scans at five tube voltages (70, 80, 100, 120, 140 kVp) with a pitch of 0.8 and a collimation of 38.4 mm. The same Monte Carlo program was also used to obtain CTDI100 and Dˆeq as well as their volume-averaged values, CTDIvol and Dˆeq,vol., Results: With other scan parameters kept constant, organ dose itself depended strongly on kVp. For the normal-weight patient model, the coefficient of variation (COV) across the five kVp values ranged between 72% and 75% for nine organs (liver, spleen, stomach, pancreas, kidneys, colon, small intestine, bladder, and ovaries) fully encompassed by the primary radiation beam. The COV generally increased with increasing patient size, ranging between 72%-77% and 76%-81% for the overweight and obese patient models, respectively. One-way analysis of variance for the effect of kVp was highly significant for all patient models (p<2×10(-26)). When organ dose was normalized by CTDIvol, the COV across kVps reduced to 5%-11%, 6%-15%, 12%-22% for the normal-weight, overweight, and obese patients, respectively. The effect of kVp was still highly significant (p=0.0001-0.004). When organ dose was normalized by Dˆeq,vol, the COV further reduced to 1%-8%, 3%-11%, 9%-19%, respectively. The effect of kVp was still significant for the obese patient model (p=0.004), but no longer significant for the normal-weight and overweight patient models (p=0.4 and 0.09, respectively). Finally, if organ dose conversion factors obtained at 120 kVp were used to approximate the values at 70 and 80 kVp, the resulting errors in the estimated organ dose were significantly reduced when the conversion factors were based on Dˆeq,vol instead of CTDIvol., Conclusions: In adult abdomen-pelvis CT, equilibrium dose-pitch product better accounts for the kVp dependence of organ dose than CTDI100.

This article aims to update the practitioner on the various techniques and interventions available to prevent or control caries during this high-risk period. The evidence to support provision of toothbrushing advice, placement of fissure sealants and fluoride varnish application is considered, along with more novel methods. An evidence-based protocol is suggested to help the practitioner determine when further intervention is required and what action to undertake. Clinical Relevance: This article aims to reinforce the need for rigorous caries prevention in an erupting permanent molar and provides an update on the evidence behind a range of clinical techniques used for this purpose.

Aim: To seek children's opinions about the acceptability of resin fissure sealant placement., Study Design: Service evaluation using a child-centred questionnaire issued to a prospective sample of consecutive hospital patients.Method Questionnaires were issued to children, aged 3 to 16 years, immediately after resin fissure sealant placement in the Paediatric Dentistry Department in Sheffield. Participants used a three-point faces scale for positive, neutral and negative responses, arranged as a Likert scale with minimal text, to rate their treatment experiences and satisfaction with the dental visit., Results: Two hundred questionnaires were returned. Overall, 96% (n = 191) recorded a positive or neutral response for the ease at which they coped with the procedure, with most children positive about having fissure sealants placed again (66%; n = 132). Further analysis demonstrated that children who had fissure sealants on a previous occasion found them easier than those having them for the first time (p <0.05, chi-squared test). Almost half of all participants where ambivalent about the taste and feeling (46%; n = 92 and 55%; n = 110 respectively). The vast majority of children were satisfied with the explanations provided by their operator., Conclusion: Most participants found having resin fissure sealants placed an overall acceptable procedure, with patient acceptance improving with increased treatment experience.

The Hall technique, a novel method of placing preformed metal crowns (PMCs) without local anaesthesia or tooth preparation, was introduced to our undergraduate dental curriculum in 2009. This study aimed to describe student experience of, and attitudes towards, PMCs before and after exposure to this new technique. Clinical data were extracted from student logbooks to determine the number of PMCs placed for cohorts graduating in 2005 (n = 55), 2009 (n = 61) and 2010 (n = 75). Five focus groups were also conducted with 29 final-year dental students. Students graduating in 2005, 2009 and 2010 had placed a mean (range) of 0.03 (0-1), 0.63 (0-5) and 1.15 (0-9) PMCs, respectively. The proportion of students who had placed a PMC increased significantly from only 1.9% in 2005 to 75% in 2010 (P < 0.05, ANOVA). Students reported some positive experiences of the Hall technique. However, concern over perceived lack of future clinical support, an anticipated increase in time and financial pressures, and the ease of use of glass-ionomer cement as an alternative were described as potential barriers to PMC use. Findings suggest that the introduction of the Hall technique has had a marked impact on the use of PMCs as a treatment modality for carious primary teeth., (© 2012 John Wiley & Sons A/S.)

Aim: To assess child and parent acceptance of preformed metal crowns (PMCs)., Study Design: This was a service evaluation using a child- and parent-centred self-report questionnaire in a convenience sample of hospital patients., Methods: Questionnaires were developed with serviceusers and issued to 98 children who had received a PMC on a primary molar within the paediatric dentistry clinic, Sheffield Dental Hospital, UK. Children used a pictorial Likert scale to rate their treatment experience and views on PMCs. Parents were also asked to complete a 5-item questionnaire, to explore their attitudes towards the PMC and how they felt their child had coped with treatment. Both children and parents were invited to comment in a free-text box on any other issues relating to PMCs. Clinical data were extrapolated from the child's dental records as follows: child's age and gender; status of clinician who had placed the PMC (staff or student), and technique for PMC placement (Hall technique or conventional)., Results: 62 questionnaires were completed (63% response rate). The mean age of the child participants was 6.6 years (SD±1.51; range=3.8-10.3), and 65% (n=40) were male. Most children found the clinical procedure acceptable with 54.8% (n=34) reporting it was 'really easy', with no significant differences according to placement technique, or the experience level of the operator (P<0.05, chi-squared test). Only 4.8% (n=3) of parents expressed strong objections to the appearance. Both children and parents felt the clinical rationale had been fully explained to them (88.7%, n=55 and 100%, n=62 respectively). Themes commonly identified from the children's accounts related to specialness, function and recollections of the treatment, with the perception that PMCs were valued for being different., Conclusions: This study revealed that PMCs were mainly viewed favourably by children and their parents. Clinicians who have been reluctant to use this restorative approach may be encouraged by these findings. However, communication and clinical expertise are paramount in ensuring children and parents have positive treatment experiences and attitudes towards PMCs.

Aim: To review recent dental child case reports to determine: 1 the main focus of the paper; 2 perceived contribution to the dental literature and, 3 involvement of the child., Study Design: Systematic review., Methods: Case reports published between 2000 and 2005 were identified using Medline via Ovid and Embase databases. Papers were reviewed to determine: their perceived value; whether they related to a single case or case series; the main dental condition; how the child was referred to, and inclusion of any child-centred input within the report., Results and Statistics: 663 case reports, from 82 journal titles, were subject to review. The majority presented a single patient (82%) and discussed a type of intervention or treatment (58%). The most common themes related to oral pathology/medicine (28%), and orthodontics (26%). Most children were referred to as 'patients' (74%) with little use of personalised terms (4%). Few reports included any child-centred input or contribution from a proxy (10% and 2% respectively). Inter- and intra-examiner repeatability for categorisation was excellent., Conclusions: The majority of child-related reports described a treatment or intervention which is surprising given the low level of case reports in the hierarchy of evidence. The child's perspective in the presenting complaint or outcome needs greater consideration.

Aim: To investigate presenting features of ectopically erupting first permanent molars and associations with other dental anomalies., Study Design: Prospective convenience study., Methods: 28 panoral radiographs were collected, over a 24-month period, of 7-11 year-old children with radiographic evidence of ectopic eruption of first permanent molars who presented to a Dental Teaching Hospital in the North of England. A further 20 radiographs were collected of matched patients with no evidence of ectopic molar eruption. All radiographs were analysed under standard conditions to record the distribution and type of ectopic eruption (if present). In addition, the presence of the following dental anomalies was noted: cleft lip and/or palate; supernumerary teeth; hypodontia, and infraocclusion of primary molars. Chi-squared analysis was performed to determine any significant differences in the frequency of these dental anomalies between ectopic molar and control groups., Results: For patients with ectopic molar eruption, the majority demonstrated ectopic eruption of either one or two first permanent molars (32% and 57% of subjects respectively). There were a similar proportion of 'jumps' and 'holds'. 92% of these were maxillary teeth and there was equal left and right distribution. Interestingly, a positive record of ectopic eruption was only documented in the dental records of 35.7% of these subjects. Children with ectopic eruption were significantly more likely to have at least one additional dental anomaly than was the case for the control group (60.7% versus 25%). Notably, primary molar infraocclusion and cleft lip/palate were significantly more frequent in the ectopic group., Conclusions: This study, the first in a British population, has identified a significant association between ectopic eruption of first permanent molars and other dental anomalies. A multifactorial aetiology is thus supported and clinicians should be alert to the co-existence of ectopic eruption and other dental anomalies.

Objective: To describe the effect of Etanercept treatment in systemic AA amyloidosis in tumour necrosis factor receptor-associated periodic syndrome (TRAPS)., Methods: Etanercept therapy was given to a 27 year old woman, with systemic amyloidosis and nephrotic syndrome, and to her 51 year old father, also affected by TRAPS, who had previously undergone renal transplant for amyloidosis. Serum SAA levels, plasma cytokines, glomerular filtration rate and serum amyloid P scanning were monitored., Results: Etanercept treatment resulted in initial clinical resolution of nephrotic syndrome in the 27 year old female. Both subjects demonstrated improvements in GFR and initial reduction or stabilisation of amyloid deposits on SAP scanning., Conclusion: Etanercept may reverse or slow the progression of systemic AA amyloidosis in subjects with C33Y TNFRSF1A mutation. Treatment may however need to be continuous and life-long to prevent progression to end stage disease.

The IQ Technology has been developed to serve as a homogeneous, universal detection platform for HTS of kinases and phosphatases. The technology is a direct, noncompetitive assay format that does not require antibodies or radioactive reagents to measure phosphorylation state. Fluorophore-labeled peptides are used as enzyme substrates, and kinase or phosphatase activity is quantitated by direct measurement of the phosphorylation state of the substrate. Phosphorylation is measured by the change in fluorescence intensity that occurs when a proprietary iron-containing compound binds specifically to phosphoryl groups on peptides. This change in observed fluorescence is proportional to the extent of phosphorylation of the fluorophore-labeled peptide. The technology provides a universal method that can be used with any peptide sequence and is insensitive to high concentrations of ATP. Inhibition at the ATP-binding site versus the phosphorylation site can be differentiated and compound selectivity identified using the same detection method as in the primary screen. The technology has been tested against a large number of detergents, organics, and other reagents found in reaction mixtures, and the detection method eliminates common issues associated with fluorescent and chromogenic compounds. The technology has been formatted for 96-, 384-, and 1,536-well microplate formats, and a representative Z' value of 0.7 was obtained. IC(50) values generated using this platform correlate with previously reported values, and screening of a small compound library was performed to evaluate the assay further.

Background: Haemodialysis patients have impaired exercise tolerance that may be related to impaired carnitine availability and/or alterations in carnitine metabolism. As carnitine metabolism is sex- and age-related, we examined plasma free and esterified carnitine concentrations, muscle strength, and estimated exercise tolerance in female (n=51) and male (n=63) patients of different ages (18-86 years)., Methods: Concentrations of free carnitine and acetylcarnitine were determined in the plasma of patients. Isometric handgrip strength was measured using a dynamometer while exercise tolerance was predicted from scores for self-reported walking distance on the level and on an incline., Results: Plasma total carnitine concentration in the females was significantly lower than that of males (35.4+/-1.3 and 42.4+/-1.4 micro mol/l, respectively, P<0.01). This was almost entirely due to the lower plasma free carnitine concentration of females when compared with the males (20.6+/-0.9 and 26.3+/-1.1 micro mol/l, respectively, P<0.05). Furthermore, plasma free carnitine concentrations were negatively correlated with age in females (r=-0.45, P<0.001) even when the linear effects of haemoglobin, albumin, body weight, time on dialysis, and muscle strength were removed from the regression analysis (partial correlation coefficient; pcc=-0.43, P=0.018), but not in the males (r=0.03, P>0.05). Isometric handgrip strength and estimated exercise tolerance on the level were lower in females than males (138.9+/-10.9 and 259.0+/-15.2 N, P<0.001; and 3.5+/-0.2 and 4.3+/-0.2, P<0.05, respectively). Isometric handgrip strength and estimated exercise tolerance (walking distance on the level and on an incline) were positively correlated with plasma free carnitine concentrations in females, but not in the males., Conclusions: There was a strong relationship between plasma free carnitine concentrations and age in female patients, but not in males. It is unlikely that the reduction in plasma free carnitine in females was a direct causative factor in their reduced exercise tolerance, but probably reflects greater muscle de-conditioning/atrophy with age in female patients.

Dialysis adequacy (Kt/V) was investigated in two groups of patients on continuous ambulatory peritoneal dialysis (CAPD). Group I consisted of patients with serum creatinine concentration above 1200 mumol/l and Group II comprised patients with serum creatinine concentration of 600 mumol/l and less. The mean Kt/V was significantly higher in Group II (Kt/V, 2.0) than in Group I (Kt/V, 1.59; p < 0.01) patients. The mean duration of CAPD was significantly longer in Group I (3.12 years) than in Group II (1.32 years; (p < 0.01) patients, and the mean total creatinine clearance for Group II patients was significantly higher than for Group I (p < 0.001) patients. There was good correlation between Kt/V and total creatinine clearance (r = 0.73; p < 0.001); and between Kt/V and normalized protein catabolic rate (NPCR, r = 0.6; p < 0.001). There was weak correlation between Kt/V and duration on dialysis, but this was statistically significant. There was no significant difference between mean NPCR and mean mid-arm muscle circumference (MAMC) in the two groups and no significant association between Kt/V and dietary inventory. Group II patients had a significantly better residual renal clearance (p < 0.0001). Pruritus was a troublesome feature in Group I patients but in both groups patients were distressed by loss of libido, insomnia and tiredness. This study revealed that Group II patients with lower creatinine concentrations had better dialysis adequacy but were on CAPD for a shorter duration than Group I and had significantly better residual renal clearance and total clearance. Muscle mass does not appear to have contributed significantly to the differences in creatinine concentration between the groups. Additional studies on peritoneal membrane function vis-à-vis solute transfer are in progress.

Polymorphonuclear leukocytes (PMN) isolated from a sub-population of patients with end-stage renal failure (ESRF) who were identified because they demonstrated impaired intracellular bacterial killing, were assayed for hydrogen peroxide activity using two different techniques capable of distinguishing between total and intracellular hydrogen peroxide generation. In an attempt to elucidate the mechanism of impaired intracellular bacterial killing further, hydrogen peroxide activity was compared to PMN isolated from patients receiving continuous ambulatory peritoneal dialysis and a control group of healthy normal volunteers. PMN from conservatively treated ESRF patients demonstrated reduced production of intracellular hydrogen peroxide (mean 37.7 +/- 4.3 fluorescence units), compared to PMN from both ESRF patients treated with continuous ambulatory peritoneal dialysis (mean 57.9 +/- 6.6 fluorescence units) and normal controls (mean 60.4 +/- 3.5 fluorescence units). This suggests that the probable mechanism of impaired bacterial intracellular killing by the PMN of conservatively treated ESRF patients involves the production of intracellular hydrogen peroxide.

Seventy ward referrals for renal disease were prospectively studied at each of two tertiary hospitals: University Hospital of the West Indies (UHWI), Kingston, Jamaica and Nottingham City Hospital (NCH), England. At UHWI, the referral population was significantly younger, 89% being less than 60 years of age compared to 40% at NCH (p < 0.05). The leading cause of acute renal failure (ARF) at UHWI was systemic lupus erythematosus (SLE) followed by acute tubular necrosis (ATN). The leading causes of ARF at NCH were ATN and obstructive uropathy. Primary renal disease and diabetes mellitus were the major causes of end-stage renal disease (ESRD) at both centres, followed by SLE and hypertension at UHWI and renovascular disease and chronic pyelonephritis at NCH. Nephrotic syndrome occurred more frequently at UHWI than at NCH but the numbers were small (p < 0.05). Mortality rates were similar among patients with ARF and nephrotic syndrome at both centres, but were higher for patients with chronic renal failure (CRF) at UHWI than at NCH (p < 0.05). Continuous ambulatory peritoneal dialysis (CAPD) was a frequent mode of renal replacement therapy at NCH (76% v 19% on haemodialysis). At UHWI, CAPD was not available and 45% of patients with ESRD were not offered maintenance dialysis because of inadequate facilities. The major difference in management and outcome between the two centres occurred in cases with CRF, suggesting that survival in patients with CRF in Jamaica could be improved if this therapeutic modality was available.

In the presence of peritoneal dialysis effluent (PDE), human polymorphonuclear leukocytes (PMN) showed reduced production of hydrogen peroxide and hypochlorous acid (H2O2 and HOCl, respectively) when at rest and when stimulated with both soluble (formylmethionyl-leucyl-phenylalanine and phorbol myristate acetate) and particulate (Staphylococcus epidermidis) agonists. This effect occurred in a concentration-dependent manner between 0 and 70%. (vol/vol) dialysis effluent. The inhibition of H2O2 and HOCl observed in resting, formy-methionylleucyphenyalanine-stimulated, and S. epidermidis-stimulated PMN was confined to a low-molecular-mass (< 10,000-Da) fraction of PDE, whereas the inhibition of the PMA response was equally dispersed throughout both low (< 10,000-Da)- and high-molecular-mass (> 10,000-Da) fractions. Human serum albumin, a major component of PDE, also inhibited H2O2 and HOCl production by PMN; however, results from cell-free systems suggested that human serum albumin was not wholly responsible for the inhibition of PMN function seen with PDE. The solute(s) responsible did not affect myloperoxidase but very rapidly scavenged H2O2 and HOCl. These data suggest that the factors capable of affecting H2O2 and HOCl production by PMN accumulate in uremia and are removed from the circulation into dialysis effluent.

Background: Erythropoietin (Epo) is an effective but expensive treatment for anaemia in patients with chronic renal failure. Hyporesponsiveness to Epo, particularly in haemodialysis patients, is most commonly due to a functional iron deficiency, which is difficult to monitor reliably., Methods: Forty-six stable haemodialysis patients, receiving Epo therapy, were commenced on regular low-dose intravenous iron (sodium ferric gluconate complex) at a dose of 62.5 mg/5 ml given as a slow injection post-dialysis twice weekly, weekly, or fortnightly, according to their serum ferritin levels. Haemoglobin, serum ferritin, Epo dose, and iron dose were measured at 6-weekly intervals over a 6-month period., Results: At the beginning of the study, 12 patients in the group had ferritin levels of less than 100 microg/l, and were thus considered to potentially have an absolute iron deficiency. The study group was therefore split into two subgroups for the purpose of analysis, i.e. the 12 patients with ferritin levels of less than 100 microg/l at the start of the study or 'low ferritin group', and the remaining 34 patients with ferritin levels of greater than 100 microg/l at the start of the study or 'normal ferritin group'. In the low ferritin group (n=12), intravenous iron therapy increased serum ferritin levels, and produced a significant rise in haemoglobin, and a significant reduction in Epo dose. (Ferritin pre-iron, median (range) 68 (20-96) microg/l; post-iron, 210.5 (91-447) microg/l, P<0. 003, Wilcoxon. Haemoglobin pre-iron, 10.05 (8.2-11.9) g/dl; post-iron, 11.0 (9.9-11.9) g/dl, P<0.03. Epo dose pre-iron, 9000 (4000-30 000)-i.u./week, P<0.05). Similar results were obtained in the normal ferritin group (n=34) following intravenous iron therapy, with significant increases in serum ferritin levels and haemoglobin concentrations, and a significant reduction in Epo dose. (Ferritin pre-iron, 176 (103-519) microg/l; post-iron, 304.5 (121-792) microg/l, P<0.0001. Haemoglobin pre-iron, 9.85 (6.5-12.8) g/dl; post-iron: 11.25 (9.9-13.3) g/dl, P<0.0001. Epo dose pre-iron, 6000 (2000-15 000) i.u./week; post-iron, 4000 (0-15 000)-i.u./week, P<0. 005)., Conclusion: Regular intravenous iron supplementation in haemodialysis patients improves the response to Epo therapy.

This study investigates the reliability of glycated haemoglobin, measured by electroendosmosis or by affinity chromatography, fructosamine, and albumin adjusted fructosamine, as indices of glycaemic control in Type 1 diabetes complicated by chronic renal failure. Twenty uraemic diabetic patients took part in the study, including 5 patients managed conservatively, 6 on CAPD, 3 on haemodialysis, and 6 renal transplant recipients. Results were compared with those from 15 diabetic subjects with normal renal function. In renal patients, there was significant correlation between glycated haemoglobin measured by electroendosmosis (r = 0.45; p = 0.04) or by affinity chromatography (r = 0.57; p = 0.01) and mean capillary blood glucose concentrations over the previous 6 weeks. The regression equations did not differ significantly between subjects with renal failure and those with normal renal function, suggesting that similar ranges can be used in interpreting glycated haemoglobin results from each group of patients. Patients on haemodialysis may be an exception; there was evidence that glycated haemoglobin may be misleadingly low in such subjects. Fructosamine correlated significantly with mean blood glucose concentrations measured over the previous week in patients with normal renal function (r = 0.75; p = 0.001), but not in patients with chronic renal failure (r = -0.1; p = 0.71). Calculation of an albumin adjusted fructosamine result failed to improve the correlation with blood glucose concentrations. The use of fructosamine cannot be recommended as an index of glycaemic control in uraemic patients.

Salt and water depletion, renal disease and urinary obstruction can all present with the syndrome of acute renal failure. Often this happens in a patient who is already ill from other causes, and management must combine seeking and correcting the cause of the renal failure, preserving life in the absence of renal function, and continuing the treatment of the coexisting problems.