Brain and Lung Imaging Correlation in Patients with COVID-19: Could the Severity of Lung Disease Reflect the Prevalence of Acute Abnormalities on Neuroimaging? A Global Multicenter Observational Study.

PURPOSE: Our aim was to study the association between abnormal findings on chest and brain imaging in patients with coronavirus disease 2019 (COVID-19) and neurologic symptoms. MATERIALS AND METHODS: In this retrospective, international multicenter study, we reviewed the electronic medical records and imaging of hospitalized patients with COVID-19 from March 3, 2020, to June 25, 2020. Our inclusion criteria were patients diagnosed with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection with acute neurologic manifestations and available chest CT and brain imaging. The 5 lobes of the lungs were individually scored on a scale of 0-5 (0 corresponded to no involvement and 5 corresponded to >75% involvement). A CT lung severity score was determined as the sum of lung involvement, ranging from 0 (no involvement) to 25 (maximum involvement). RESULTS: A total of 135 patients met the inclusion criteria with 132 brain CT, 36 brain MR imaging, 7 MRA of the head and neck, and 135 chest CT studies. Compared with 86 (64%) patients without acute abnormal findings on neuroimaging, 49 (36%) patients with these findings had a significantly higher mean CT lung severity score (9.9 versus 5.8, P < .001). These patients were more likely to present with ischemic stroke (40 [82%] versus 11 [13%], P < .0001) and were more likely to have either ground-glass opacities or consolidation (46 [94%] versus 73 [84%], P = .01) in the lungs. A threshold of the CT lung severity score of >8 was found to be 74% sensitive and 65% specific for acute abnormal findings on neuroimaging. The neuroimaging hallmarks of these patients were acute ischemic infarct (28%), intracranial hemorrhage (10%) including microhemorrhages (19%), and leukoencephalopathy with and/or without restricted diffusion (11%). The predominant CT chest findings were peripheral ground-glass opacities with or without consolidation. CONCLUSIONS: The CT lung disease severity score may be predictive of acute abnormalities on neuroimaging in patients with COVID-19 with neurologic manifestations. This can be used as a predictive tool in patient management to improve clinical outcome.

Effect of predation on the mechanical properties and detachment of MABR biofilms.

The membrane-aerated biofilm reactor (MABR) is an emerging wastewater treatment technology that uses O2-supplying membranes as a biofilm support. Because O2 is supplied from the biofilm base instead of the bulk liquid, MABR biofilms have distinct microbial community structures and behavior. Past research showed that protozoan predation in MABR biofilms can greatly increase biofilm porosity, producing a void layer at the base of the biofilm. We hypothesized that this void layer could weaken the biofilm and promote sloughing, and investigated this with heterotrophic MABR biofilms. A rheometer was used to measure biofilm mechanical strength, and MABR flow cells were used to explore detachment. MABRs supplied with cycloheximide, a protozoan inhibitor, were used as controls. Predation increased the internal void ratio from 6 ± 7% to 50 ± 16%. The storage modulus was 1,780 ± 1,180 Pa with predation condition, compared to 9,800 ± 4,290 Pa for the control. Similarly, the loss modulus was 1,580 ± 729 Pa with predation and 363 ± 189 Pa for the control. When subjected to an increased flow, the biofilm loss was 44 ± 24% for the flow cell with predation, while only 7 ± 9% for the control. This research shows that predation can have an important impact on biofilm porosity in MABRs, reducing the mechanical strength and increasing detachment. Understanding this phenomenon can help develop more effective biofilm control strategies in MABRs.

[Posterior reversible leukoencephalopathy syndrome in a patient with Parkinson's disease and initial psychiatric symptoms: a complex clinical presentation]. / Sindrome de leucoencefalopatia posterior reversible en un paciente con enfermedad de Parkinson y sintomatologia inicial psiquiatrica: una presentacion clinica compleja.

INTRODUCTION: The relevance of the immunosuppressive drug tacrolimus in the prevention of rejection and graft-versus-host disease in transplanted patients is beyond all doubt. However, tacrolimus often has neurotoxic effects, including severe conditions such as posterior reversible leukoencephalopathy syndrome. CASE REPORT: A 75-year-old male who had undergone a kidney transplantation five years earlier, for which he was receiving treatment with tacrolimus and mycophenolate. He also had advanced Parkinson's disease, treated with several dopamine agonists. The patient visited the emergency department after a week-long history of visual hallucinations, delirium, expansive mood, confusion and headache. The focal psychogeriatric examination revealed psychosis secondary to dopaminergic agonists as the first diagnostic option, without excluding other possible iatrogenic causes despite the tacrolimus being within the therapeutic range (8.3 ng/mL). Both cranial computed tomography, which did not show any significant findings, and a magnetic resonance scan, in which a bilateral parietooccipital oedema was observed, were performed, this latter finding being compatible with posterior reversible leukoencephalopathy syndrome. While the patient was in hospital, tacrolimus was replaced by everolimus, and the dopaminergic medication was adjusted, resulting in a swift and full remission of the clinical signs and symptoms. CONCLUSIONS: The diagnosis of posterior reversible leukoencephalopathy syndrome should be considered in patients with a history of organ transplantation treated with immunosuppressive drugs who have an acute onset condition with neurological or psychiatric symptoms.

TITLE: Sindrome de leucoencefalopatia posterior reversible en un paciente con enfermedad de Parkinson y sintomatologia inicial psiquiatrica: una presentacion clinica compleja.Introduccion. La relevancia del farmaco inmunosupresor tacrolimus en la prevencion del rechazo y la enfermedad de injerto contra huesped en pacientes trasplantados es indiscutible. Sin embargo, con frecuencia, el tacrolimus presenta efectos neurotoxicos, incluyendo cuadros graves, como el sindrome de leucoencefalopatia posterior reversible. Caso clinico. Varon de 75 años, con antecedentes de trasplante renal hace cinco años, en tratamiento con tacrolimus y micofenolato, y de enfermedad de Parkinson avanzada, en tratamiento con varios agonistas dopaminergicos. Acudio a urgencias por un cuadro de una semana de evolucion consistente en alucinaciones visuales, delirios, animo expansivo, confusion y cefalea. La exploracion psicogeriatrica por focos mostro como primera opcion diagnostica una psicosis secundaria a agonistas dopaminergicos, sin excluir otras causas yatrogenas a pesar de encontrarse el tacrolimus en el rango terapeutico (8,3 ng/mL). Se realizaron una tomografia computarizada craneal, que no mostro hallazgos significativos, y una resonancia magnetica, en la que se visualizo un edema parietooccipital bilateral, hallazgo compatible con un sindrome de leucoencefalopatia posterior reversible. Durante el ingreso se sustituyo el tacrolimus por everolimus y se ajusto la medicacion dopaminergica, con lo que se produjo de forma rapida una remision completa del cuadro. Conclusiones. El diagnostico de sindrome de leucoencefalopatia posterior reversible debe considerarse en los pacientes con antecedentes de trasplante de organo en tratamiento con farmacos inmunosupresores que presentan un cuadro de instauracion aguda con sintomas neurologicos o psiquiatricos.

Predation creates unique void layer in membrane-aerated biofilms.

The membrane-aerated biofilm reactor (MABR) is a novel wastewater treatment technology based on oxygen-supplying membranes. The counter diffusion of oxygen and electron donors in MABRs leads to unique behavior, and we hypothesized it also could impact predation. We used optical coherence tomography (OCT), microsensor analyses, and mathematical modeling to investigate predation in membrane-aerated biofilms (MABs). When protozoa were excluded from the inoculum, the MAB's OCT-observable void fraction was around 5%. When protozoa were included, the void fraction grew to nearly 50%, with large, continuous voids at the base of the biofilm. Real-time OCT imaging showed highly motile protozoa in the voids. MABs with protozoa and a high bulk COD (270 mg/L) only had 4% void fraction. DNA sequencing revealed a high relative abundance of amoeba in both high and low-COD MABs. Flagellates were only abundant in the low-COD MAB. Modeling also suggested a relationship between substrate concentrations, diffusion mode (co- or counter-diffusion), and biofilm void fraction. Results suggest that amoeba proliferate in the biofilm interior, especially in the aerobic zones. Voids form once COD limitation at the base of MABs allows predation rates to exceed microbial growth rates. Once formed, the voids provide a niche for motile protozoa, which expand the voids into a large, continuous gap. This increases the potential for biofilm sloughing, and may have detrimental effects on slow-growing, aerobic microorganisms such as nitrifying bacteria.

A combination of nanosystems for the delivery of cancer chemoimmunotherapeutic combinations: 1-Methyltryptophan nanocrystals and paclitaxel nanoparticles.

IDO is an enzyme that tumors use to create a state of immunosupression. 1-d-methyltryptophan (1-MT) is an IDO pathway inhibitor. After being successfully evaluated in preclinical studies, current clinical trials are actually analyzing its efficacy as monotherapy or in combination with multiple chemotherapeutic agents such as paclitaxel. 1-MT very poor solubility in water and many other solvents precludes its ease parenteral administration. It is currently administered by oral route because high daily doses were well-tolerated and effectively inhibited the IDO activity although only 25% of dose was recovered in plasma. The present work describes the preparation and characterization of 1-MT nanocrystals in order to enhance its solubility, dissolution rate, biodisponibility as well as facilitate its administration by parenteral route. A bottom-down approach of nanoprecipitation with an antisolvent was used for the fabrication of the nanocrystals and the choice of stabilizers was critical for reducing the size. Thermal analysis and x-ray diffraction indicated modifications in the drug crystalline state by the process. Through the reduction size and crystalline state modifications the dissolution characteristics of raw material were significantly increased. In a Lewis Lung cancer mice model, the nanocrystals strategy facilitated the sc administration and its antitumoral activity was similar to that of i.v. paclitaxel. The best efficacy was achieved when sc 1-MT nanocrystals were administered in combination with oral paclitaxel loaded in poly(anhydride) nanoparticles. Take together, 1-MT nanocrystals delivery performs a nanotechnological strategy suitable to modify the current route and schedule for its administration.

Periodic venting of MABR lumen allows high removal rates and high gas-transfer efficiencies.

The membrane-aerated biofilm reactor (MABR) is a novel treatment technology that employs gas-supplying membranes to deliver oxygen directly to a biofilm growing on the membrane surface. When operated with closed-end membranes, the MABR provides 100-percent oxygen transfer efficiencies (OTE), resulting in significant energy savings. However, closed-end MABRs are more sensitive to back-diffusion of inert gases, such as nitrogen. Back-diffusion reduces the average oxygen transfer rates (OTR), consequently decreasing the average contaminant removal fluxes (J). We hypothesized that venting the membrane lumen periodically would increase the OTR and J. Using an experimental flow cell and mathematical modeling, we showed that back-diffusion gas profiles developed over relatively long timescales. Thus, very short ventings could re-establish uniform gas profiles for relatively long time periods. Using modeling, we systematically explored the effect of the venting interval (time between ventings). At moderate venting intervals, opening the membrane for 20 s every 30 min, the venting significantly increased the average OTR and J without substantially impacting the OTEs. When the interval was short enough, in this case shorter than 20 min, the OTR was actually higher than for continuous open-end operation. Our results show that periodic venting is a promising strategy to combine the advantages of open-end and closed end operation, maximizing both the OTR and OTE.

Feedback and clinical practice improvement: A tool to assist workplace supervisors and students.

In work integrated learning, students may report difficulties applying theory learned at university to clinical practice. One contributing factor may be students' inability to engage in meaningful reflection and self-correcting behaviours. This paper reports the evaluation of a tool, process and resources developed to assist students to reflect on feedback and engage in self-assessment. Students were assisted to develop self-assessment skills by reflecting on, and engaging with feedback from previous workplace experiences to develop goals, learning outcomes and strategies to improve performance with mostly positive results. A secondary aim was to identify common learning strategies or barriers that impacted on student outcomes. Four themes emerged from the qualitative data: 1) preparing for clinical learning, 2) relationships and engagement levels, 3) shared awareness and, 4) developing clinical practice. Overall students felt the tool assisted them to narrow their attention on what needed to be improved. While supervisors believed the tool helped them to focus on specific needs of each student. Common barriers to clinical practice improvement related to a lack of opportunity in some settings, and lack of staff willingness to support students to achieve identified goals. Students and supervisors found the use of the tools beneficial and assisted students to demonstrate a greater understanding of how to apply feedback received to support their learning in the clinical environment.

[Mucopenetrating nanoparticles: vehicles for the oral administration of paclitaxel]. / Nanoparticules mucopénétrantes: véhicules pour l'administration orale du paclitaxel.

Paclitaxel is an anticancer drug used as solution for perfusion for the treatment of certain types of cancers. In the last years, a number of strategies have been proposed for the development of an oral formulation of this drug. However, this task is quite complicated due to the poor aqueous solubility of paclitaxel as well as the fact that this compound is substrate of the intestinal P-glycoprotein and the cytochrome P450 enzymatic complex. In this work, we have developed pegylated nanoparticles with mucopenetrating properties in order to conduct paclitaxel onto the surface of the enterocyte. These nanoparticles displayed a size of about 180 nm and a drug loading close to 15% by weight. The pharmacokinetic study in mice has shown that these nanoparticles were capable to offer therapeutic plasma levels of paclitaxel up to 72 hours. In addition, the oral relative bioavailability of paclitaxel when loaded in nanoparticles pegylated with poly(ethylene glycol) 2000 (PEG) was found to be 85%. In a subcutaneous model of tumour in mice, these pegylated nanoparticles administered orally every 3 days have demonstrated a similar efficacy than Taxol® administered intravenously every day during 9 days. All of these results suggested that these pegylated nanoparticles were capable to cross the mucus layer of the gut and, then, reach the surface of the enterocytes. The PEG molecules would facilitate the adhesion of nanoparticles to this epithelial surface, minimise the pre-systemic metabolism of paclitaxel and, thus, promote its absorption.

Improving access to quality clinical nurse teaching--a partnership between Australia and Vietnam.

Until recently, standards to guide nursing education and practice in Vietnam were nonexistent. This paper describes the development and implementation of a clinical teaching capacity building project piloted in Hanoi, Vietnam. The project was part of a multi-component capacity building program designed to improve nurse education in Vietnam. Objectives of the project were to develop a collaborative clinically-based teaching model that encourages evidence-based, student-centred clinical learning. The model incorporated strategies to promote development of nursing practice to meet national competency standards. Thirty nurse teachers from two organisations in Hanoi participated in the program. These participants attended three workshops, and completed applied assessments, where participants implemented concepts from each workshop. The assessment tasks were planning, implementing and evaluating clinical teaching. On completion of the workshops, twenty participants undertook a study tour in Australia to refine the teaching model and develop an action plan for model implementation in both organisations, with an aim to disseminate the model across Vietnam. Significant changes accredited to this project have been noted on an individual and organisational level. Dissemination of this clinical teaching model has commenced in Ho Chi Minh, with further plans for more in-depth dissemination to occur throughout the country.

Association between multiple sclerosis and Candida species: evidence from a case-control study.

Candida infection among multiple sclerosis (MS) patients has not been studied in depth. We determined whether there is an association between serological evidence of Candida infection and MS. Blood specimens were obtained from 80 MS patients and 240 matched controls. Immunofluorescence analysis and ELISA were used to detect Candida species antibodies and slot-blot to detect antigens. Using immunofluorescence analysis, moderate to high concentrations of serum antibodies to Candida famata were present in 30 (37.5%) MS patients vs. 30 (12.5%) controls (p < 0.001). Results for Candida albicans were 47.5% (38/80) in MS patients vs. 21.3% (51/240) in controls (p < 0.001), for Candida parapsilosis 37% (28/80) vs. 17.1% (41/240) (p < 0.001) and for Candida glabrata 46.3% (37/80) vs. 17.5% (42/240) (p < 0.001), respectively. After adjusting for age and gender, the odds ratios (95% confidence intervals) for MS, according to the presence of Candida antigens were: 2.8 (0.3-23.1, p = 0.337) for Candida famata; 1.5 (0.7-3.4, p = 0.290) for Candida albicans; 7.3 (3.2-16.6, p < 0.001) for Candida parapsilosis; and 3.0 (1.5-6.1, p = 0.002) for Candida glabrata. The results were similar after excluding ten patients on immunosuppressants. The results of this single study suggest that Candida species infection may be associated with increased odds of MS.

Histamine-N-methyl transferase polymorphism and risk for multiple sclerosis.

BACKGROUND: Histamine N-methyltransferase (HNMT) is the main metabolizing enzyme of histamine (a mediator of inflammation implicated in the pathogenesis of multiple sclerosis-MS) in the CNS. We have investigated the possible association between a single nucleotide polymorphism of the HNMT (chromosome 2q22.1), that causes the amino acid substitution Thr105Ile (decreasing enzyme activity) and the risk for MS. METHODS: We studied the frequency of the HNMT genotypes and allelic variants in 228 MS patients and 295 healthy controls using a PCR-RLFP method. RESULTS: The frequencies of the HNMT genotypes and allelic variants did not differ significantly between MS patients and controls, and were unrelated with the age of onset of MS, gender, and course of MS. CONCLUSION: The HNMT polymorphism is not related with the risk for MS.

[Opinions on the organisation of health care in strokes. A survey among hospital medical directors in Spain]. / Opinión sobre la organización asistencial en el ictus. Encuesta a directores médicos hospitalarios en España.

INTRODUCTION: Therapy to treat strokes has changed dramatically. Around 70 years ago, it could not be treated and today it is a medical emergency. Awareness of this change has still not reached many layers of the medical or health care professions or of society itself. AIM: To use a survey to evaluate the attitudes of medical directors and hospital specialists towards the problems involved in the inpatient care of stroke patients. Materials and methods. A survey was carried out by means of a pilot study in hospitals in Madrid with specific sub-surveys for medical managers in charge of neurology departments, neurosurgery services and stroke units. These surveys were sent out to 108 acute care hospitals with over 250 beds in 2003-2004. RESULTS: Only the results of the survey administered by medical directors are analysed. Finally, 52 surveys were obtained from 108 hospitals. Information was collected about several aspects of stroke patients, including care in hospital emergency department, admission to hospital, rehabilitation treatment and staffing in stroke units. Care of stroke patients was given a significantly more positive score (better stroke care) by medical directors than by hospital neurologists. CONCLUSIONS: The survey revealed a great care burden from stroke in hospital emergency departments and from hospital admissions, deficits in neurological duty services and in the capacity to perform fibrinolysis and, above all, in stroke units. The data obtained show that medical directors should improve their attitudes with regard to the care of stroke patients.

Opinión sobre la organización asistencial en el ictus. Encuesta a directores médicos hospitalarios en España / Opinions on the organisation of health care in strokes. A survey among hospital medical directors in Spain

Introducción. La terapia del ictus ha cambiado dramáticamente. Hace 70 años no tenía tratamiento y, en la actualidad, es una urgencia médica. La conciencia de este cambio no ha llegado a muchos estamentos médicos o sanitarios ni a la sociedad. Objetivo. Evaluar las actitudes, mediante encuesta, de directores médicos y de especialistas médicos hospitalarios hacia la problemática asistencial hospitalaria del paciente con ictus. Materiales y métodos. Se desarrolló una encuesta por medio de un estudio piloto en hospitales de Madrid con subencuestas específicas para directores médicos, responsables de los servicios de neurología, neurocirugía y de las unidades de ictus. Se remitieron estas encuestas a 108 hospitales de enfermos agudos mayores de 250 camas en 2003-2004. Resultados. Sólo se analizan los resultados de la encuesta a los directores médicos. Se obtuvieron 52 encuestas de 108 hospitales. Se obtuvo información sobre varios aspectos de los pacientes con ictus: atención en la urgencia hospitalaria, ingreso en el hospital, tratamiento de rehabilitación y dotación de unidades ictus. La atención al paciente con ictus mereció una valoración por parte de los directores médicos significativamente más positiva (mejor atención al ictus) que por parte de los neurólogos hospitalarios. Conclusiones. La encuesta mostró gran carga asistencial de ictus en urgencias hospitalarias y de ingresos hospitalarios, déficit de guardias neurológicas y de capacidad para la realización de fibrinólisis y, sobre todo, de unidades de ictus. Los datos obtenidos indican que los directores médicos deberían mejorar sus actitudes sobre la asistencia al paciente con ictus (AU)

Introduction. Therapy to treat strokes has changed dramatically. Around 70 years ago, it could not be treated and today it is a medical emergency. Awareness of this change has still not reached many layers of the medical or health care professions or of society itself. Aim. To use a survey to evaluate the attitudes of medical directors and hospital specialists towards the problems involved in the inpatient care of stroke patients. Materials and methods. A survey was carried out by means of a pilot study in hospitals in Madrid with specific sub-surveys for medical managers in charge of neurology departments, neurosurgery services and stroke units. These surveys were sent out to 108 acute care hospitals with over 250 beds in 2003-2004. Results. Only the results of the survey administered by medical directors are analysed. Finally, 52 surveys were obtained from 108 hospitals. Information was collected about several aspects of stroke patients, including care in hospital emergency department, admission to hospital, rehabilitation treatment and staffing in stroke units. Care of stroke patients was given a significantly more positive score (better stroke care) by medical directors than by hospital neurologists. Conclusions. The survey revealed a great care burden from stroke in hospital emergency departments and from hospital admissions, deficits in neurological duty services and in the capacity to perform fibrinolysis and, above all, in stroke units. The data obtained show that medical directors should improve their attitudes with regard to the care of stroke patients (AU)

[Solitary costal plasmacytoma: a rare cause of subacute demyelinating polyradiculoneuropathy]. / Plasmocitoma solitario costal: causa excepcional de polirradiculoneuropatía desmielinizante subaguda.

INTRODUCTION: The solitary plasmacytoma (SP) is a non-frequent, localized variant of multiple myeloma with a single bone lesion and earlier appearance. Polyradiculoneuropathy is the most frequent neurological manifestation. We report the case of a young male who developed a subacute demyelinating polyradiculoneuropathy as the initial symptomatology of a costal SP, which constitutes an extremely infrequent association, given age and site of the lesion. CASE REPORT: A 32-year old, previously healthy, man presented with a one month history of progressive symmetrical paraparesis and paresthesias in feet. The neurological examination revealed 4/5 paraparesis, global arreflexia and hypopalesthesia in legs. Cerebrospinal fluid examination revealed elevated proteins (83 mg/dl) with normal cell count and glucose content. Investigations showed high levels of beta(2)-microglobulin (3 mg/l), and a monoclonal IgG lambda gammapathy. The chest X-ray and thoracic CT revealed an osteolytic lesion in the left third rib. Nerve conduction studies showed sensitive and motor polyneuropathy with secondary axonal degeneration. Bone marrow biopsy was normal. Second and third left ribs were excised, revealing a pathologic diagnosis of plasmacytoma. The patient became asymptomatic after corticosteriod administration lesion excision and local radiotherapy. Conclusions. Subacute demyelinating polyradiculoneuropathy can be due to multiple causes. SP can be one of its etiologies and occur at infrequent ages and localizations.

Plasmocitoma solitario costal: causa excepcional de pollirradiculoneuropatía desmielinizante subaguda / Solitary costal plasmacytoma: a rare cause of subacute demyelinating polyradiculoneuropathy

Introducción. El plasmocitoma solitario (PS) es una variante infrecuente del mieloma múltiple caracterizado por una lesión ósea única y aparición más temprana. La manifestación neurológica más frecuente es la polirradiculoneuropatía. Presentamos el caso de un paciente joven con una polirradiculopatía desmielinizante subaguda como inicio de un PS costal, lo que constituye un hecho extremadamente infrecuente dada la edad y localización de la lesión. Caso clínico. Varón de 32 años sano que ingresó por cuadro subagudo de un mes de evolución de paraparesia y parestesias en los pies. En la exploración neurológica se objetivó una paraparesia 4/5 con arreflexia universal y disminución de la sensibilidad profunda en los pies. El estudio del líquido cefalorraquídeo mostró una proteinorraquia de 83 mg/dl sin pleocitosis. Tenía una beta (2)-microglobulina de 3 mg/l y un pico monoclonal IgG lambda. La radiografía costal y la TC toracoabdominal evidenciaron una lesión única de características líticas en el tercer arco costal izquierdo. El estudio neurofisiológico descubrió una polineuropatía sensitivomotora mixta con degeneración axonal secundaria de predominio en miembros inferiores. La biopsia de médula ósea fue normal. Se realizó la exéresis de la lesión costal con resultado patológico de plasmocitoma. Tras la administración de corticoides, la exéresis de la lesión y radioterapia local se consiguió la desaparición de la sintomatología. Conclusiones. Las polirradiculoneuropatías desmielinizantes subagudas tienen un amplio espectro etiológico. Aunque extremadamente raro, el PS puede ser una causa de las mismas y presentarse tanto en edades como en localizaciones infrecuentes (AU)

Introduction: The solitary plasmacytoma (SP) is a non-frequent, localized variant of multiple myeloma with a single bone lesion and earlier appearance. Polyradiculoneuropathy is the most frequent neurological manifestation. We report the case of a young male who developed a subacute demyelinating polyradiculoneuropathy as the initial symptomatology of a costal SP, which constitutes an extremely infrequent association, given age and site of the lesion. CASE Report: A 32-year old, previously healthy, man presented with a one month history of progressive symmetrical paraparesis and paresthesias in feet. The neurological examination revealed 4/5 paraparesis, global arreflexia and hypopalesthesia in legs. Cerebrospinal fluid examination revealed elevated proteins (83 mg/dl) with normal cell count and glucose content. Investigations showed high levels of beta (2)-microglobulin (3 mg/l), and a monoclonal IgG lambda gammapathy. The chest X-ray and thoracic CT revealed an osteolytic lesion in the left third rib. Nerve conduction studies showed sensitive and motor polyneuropathy with secondary axonal degeneration. Bone marrow biopsy was normal. Second and third left ribs were excised, revealing a pathologic diagnosis of plasmacytoma. The patient became asymptomatic after corticosteriod administration lesion excision and local radiotherapy. Conclusions. Subacute demyelinating polyradiculoneuropathy can be due to multiple causes. SP can be one of its etiologies and occur at infrequent ages and localizations (AU)

Differential induction of macrophage recognition of carrier erythrocytes by treatment with band 3 cross-linkers.

Mouse native and hypotonically loaded erythrocytes were treated with two cross-linking reagents: bis(sulphosuccinimidyl)suberate (BS3)- and 3,3'-dithiobis-(sulphosuccinimidyl propionate) (DTSP), excluding clustering agents. Microscopic analyses revealed that band 3 cross-linked native and hypotonically loaded erythrocytes are more strongly recognized by peritoneal macrophages than native and loaded erythrocytes as a result of the cross-linking of band 3 protein in accordance with studies in vivo. Macrophage-recognition analyses of 51Cr-labelled erythrocytes also demonstrated increased recognition of cross-linked and cross-linked loaded erythrocytes. This shows that the only action of these two band 3 cross-linkers on mouse erythrocytes promotes recognition by macrophages without requiring the use of clustering agents. The extent of recognition of BS3 cross-linked and cross-linked loaded erythrocytes by macrophages is dependent on the presence or absence of homologous serum or immunoglobulins. In contrast, the presence of serum factors or IgG in the incubation medium did not seem to influence the recognition of DTSP-modified erythrocytes by macrophages. These results seem to indicate a different mechanism of recognition for the erythrocytes modified with either one or the other band 3 cross-linker. In summary, the unique use of both band 3 cross-linkers procedures can be used to target carrier erythrocytes conveying active compounds to macrophages, with possible therapeutical applications. Different mechanisms of induction of macrophage recognition by these band 3 cross-linkers could reveal differential actions on erythrocytes or the involvement of different factors in the recognition process.

Cross-linking treatment of loaded erythrocytes increases delivery of encapsulated substance to macrophages.

Previous investigation has shown that osmotically loaded erythrocytes can act as drug carriers in systemic circulation, whereas chemically modified erythrocytes can be targeted to organs of the mononuclear phagocytic system because of changes introduced in the membrane that are recognized by macrophage cells. In this study we have examined the delivery of 125I-labelled carbonic anhydrase (125I-CA) carried by mouse erythrocytes, either loaded, or loaded and cross-linked with bis(sulphosuccinimidyl)suberate (BS3) and 3,3'-dithiobis-(sulphosuccinimidyl propionate), into homologous peritoneal macrophages maintained in culture. The hypotonically loaded mouse erythrocytes show a slight recognition by macrophages, similar to native erythrocytes. CA loaded into erythrocytes is thus delivered to a limited extent into macrophages. Neither the number of recognized loaded 51Cr-labelled erythrocytes nor the amount of delivered 125I-CA is affected by the presence of serum components or IgG. In contrast, cross-linking these loaded erythrocytes results in a greater phagocytosis by macrophages as assessed by microscopic observations, producing a markedly increased amount of targeted enzyme. The amount of CA delivered into macrophages, after BS3 cross-linker treatment of erythrocytes, is dependent on the presence of serum components in the incubation medium. Thus these cross-linking treatments improve the capacity of loaded mouse erythrocytes to deliver significant amounts of targeted enzyme to macrophage cells, increasing the therapeutic potential of carrier erythrocytes.