Comparing the Results of Written Testing for Advanced Cardiac Life Support Teaching Using Team-based Learning and the "Flipped Classroom" Strategy.

Objectives We sought to further determine whether cognitive test results changed for advanced cardiac life support (ACLS) taught in the team-based learning/flipped classroom format (TBL/FC) versus a lecture-based (LB) control. Methods We delivered 2010 ACLS to two classes of fourth-year medical students in the TBL/FC format (2015-2016), compared to three classes in the LB format (2012-2014). There were 27.5 hours of instruction for the TBL/FC model (TBL - 10.5 hours, podcasts - nine hours, small-group simulation - eight hours), and 20 hours (lectures - 12 hours, simulation - eight hours) in LB. We taught TBL for 13 cardiac cases while LB had none. Didactic content and seven simulated cases were the same in lecture (2012-2014) or in podcast formats (2015-2016). Testing was the same using 50 multiple-choice (MC) format questions, 20 rhythm-matching questions, and seven fill-in management of simulated cases. Results Some 468 students enrolled in the course 259 (55.4%) in the LB format in 2012-2014, and 209 (44.6%) in the TBL/FC format in 2015-2016. The scores for two out of three tests (MC and fill-in) increased with TBL/FC. Combined, median scores increased from 93.5% (IQR 90.6, 95.4) to 95.1% (92.5, 96.8, p = 0.0001). More students did not pass one of three tests with LB versus TBL/FC (24.7% versus 18.2%), and two or three parts of the test (8.1% versus 4.3%, p = 0.01). On the contrary, 77.5% passed all three with TBL/FC versus 67.2% with LB (change 10.3%, 95% CI 2.2%-18.2%). Conclusion TBL/FC teaching for ACLS improved written test results compared with the LB format.

Thrombosis of Inferior Vena Cava Diagnosed Using Point-of-Care Ultrasound After Pediatric Near-Syncope.

BACKGROUND: Venous thromboembolism (VTE) is extremely rare but under recognized in the pediatric population. Although the literature on the use of ultrasound to detect VTEs in adults is plentiful, little has been documented on its use in the pediatric population. CASE REPORT: We present a case of a healthy 16-year-old female who presented to our emergency department with 3 months of dyspnea on exertion and one episode of near-syncope. Point-of-care cardiac ultrasound identified an inferior vena cava thrombosis. Subsequent computed tomography angiography diagnosed concurrent bilateral pulmonary emboli (PE). The patient's identical twin sister presented with similar symptoms shortly thereafter and was also diagnosed with VTE and bilateral PE. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case demonstrates an instance of VTE and pulmonary embolism in twin adolescent girls. Physical examination findings, electrocardiogram, chest x-ray study, and several previous evaluations did not reveal the diagnosis. Point of care ultrasound was used to correctly diagnosis VTE and for heightened concern for a pulmonary embolism.

Flipping the Advanced Cardiac Life Support Classroom with Team-based Learning: Comparison of Cognitive Testing Performance for Medical Students at the University of California, Irvine, United States.

PURPOSE: It aimed to find if written test results improved for advanced cardiac life support (ACLS) taught in flipped classroom/team-based Learning (FC/TBL) vs. lecture-based (LB) control in University of California-Irvine School of Medicine, USA. METHODS: Medical students took 2010 ACLS with FC/TBL (2015), compared to 3 classes in LB (2012-14) format. There were 27.5 hours of instruction for FC/TBL model (TBL 10.5, podcasts 9, small-group simulation 8 hours), and 20 (12 lecture, simulation 8 hours) in LB. TBL covered 13 cardiac cases; LB had none. Seven simulation cases and didactic content were the same by lecture (2012-14) or podcast (2015) as was testing: 50 multiple-choice questions (MCQ), 20 rhythm matchings, and 7 fill-in clinical cases. RESULTS: 354 students took the course (259 [73.1%] in LB in 2012-14, and 95 [26.9%] in FC/TBL in 2015). Two of 3 tests (MCQ and fill-in) improved for FC/TBL. Overall, median scores increased from 93.5% (IQR 90.6, 95.4) to 95.1% (92.8, 96.7, P=0.0001). For the fill-in test: 94.1% for LB (89.6, 97.2) to 96.6% for FC/TBL (92.4, 99.20 P=0.0001). For MC: 88% for LB (84, 92) to 90% for FC/TBL (86, 94, P=0.0002). For the rhythm test: median 100% for both formats. More students failed 1 of 3 tests with LB vs. FC/TBL (24.7% vs. 14.7%), and 2 or 3 components (8.1% vs. 3.2%, P=0.006). Conversely, 82.1% passed all 3 with FC/TBL vs. 67.2% with LB (difference 14.9%, 95% CI 4.8-24.0%). CONCLUSION: A FC/TBL format for ACLS marginally improved written test results.

La fecundación in vitro, un derecho negado en colombia: a denied rigth in colombia / In vitro fecundation: um direito negado na colômbia / A fecundação in vitro

La oportunidad convertida en posibilidad de conformar una familia, como núcleo esencial de la sociedad, no solo está dada por la unión de un hombre con una mujer o, como en los últimos pronunciamientos constitucionales, por la unión de parejas del mismo sexo, quienes, por voluntad personal y autonomía deciden no tener hijos o tenerlos sin limitación alguna al número de ellos. Sin embargo, no todas las personas tienen las capacidades biológicas óptimas para la fecundación y procreación de manera natural, por lo cual deben acudir a realizarse diferentes tratamientos médicos especializados para tener una expectativa de crear su prole o descendencia, con la ayuda de los avances científicos, en un estado donde el acceso a la biotecnología tiene unos costos elevados, que hacen que su acceso sea limitado. Dentro de estos tratamientos médicos se encuentra la Fecundación In Vitro (FIV), procedimiento mediante el cual, la fecundación del óvulo por el espermatozoide se hace en laboratorio y es implantado en el útero y no de manera natural, es decir, a través de una relación sexual, tratamiento que tiene unos costos bastante onerosos. La Corte Constitucional en sentencias de tutela ha señalado algunos casos excepcionales para autorizar la FIV, pero supeditados a negligencias de las EPS y a una correlación entre la enfermedad y la vida, a partir de la conexidad, más no por la libre determinación de tener hijos, argumentando, para justificar esta discriminación en que el Estado Colombiano no puede soportar los costos de este tipo de tratamientos, ya que no se encuentran incluidos en el (Plan Obligatorio de Salud) POS, indicado que cada pareja o mujer que quiera constituir una familia debe sufragar, por sus propios medios los costos del tratamiento y finalmente señalando que existe la adopción como posibilidad para tener hijos, negando así el derecho a tener hijos de sangre.

The opportunity of building a family, as society basic core, is not only given by the marriage of a man and a woman. The last constitutional declarations also include same sex couples and people who are willing by their personal choice and autonomy, without limitations in the quantity of children. Nevertheless, not all the people have the biological capacity for fecundation and procreation. That is why they have to look up for diverse treatments at specialized medical centers to be able to create a family. In vitro fecundation (IVF) is one of the treatments offered. This procedure consists in the laboratory manipulation to inseminate the ovule with the spermatozoid and implant the fertilized ovule in the uterus. In Colombia, the access to these kind of treatment is limited, expensive and is not covered by the health insurance system. Some Constitutional Court precepts have pointed out that it could be some exceptional cases where the Health System has the obligation to cover the IVF expenses, due to negligence and a correlation between sickness and life. The precepts do not consider the free willing of having children and also states that Colombia is not able to support the expenses of the IVF, because is not included in the basic plan of health coverage. Finally suggesting that the adoption is a more feasible opportunity and denying the right of having children by blood.

A oportunidade de construir uma família, como núcleo básico da sociedade, não é apenas dada pelo casamento de um homem e uma mulher. As últimas declarações constitucionais também incluem casais do mesmo sexo e pessoas que estão dispostas por sua escolha pessoal e autonomia, sem limitações na quantidade de crianças. No entanto, nem todas as pessoas têm a capacidade biológica para a fecundação e procriação. É por isso que eles têm que procurar por diversos tratamentos em centros médicos especializados para ser capaz de criar uma familia. A fecundação in vitro (IVF) é um dos tratamentos oferecidos. Este procedimento consiste na manipulação laboratorial para inseminar o óvulo com o espermatozóide e implantar o óvulo fecundado no útero. Na Colômbia, o acesso a esse tipo de tratamento é limitado, caro e não é coberto pelo sistema de seguro de saúde. Alguns preceitos do Tribunal Constitucional apontaram que podem ser alguns casos excepcionais em que o Sistema de Saúde tem a obrigação de cobrir as despesas de FIV, por negligência e correlação entre doença e vida. Os preceitos não consideram a vontade livre de ter filhos e também afirma que a Colômbia não é capaz de suportar as despesas da FIV, porque não está incluído no plano básico de cobertura de saúde. finalmente é notar que não há a adoção como uma possibilidade de ter filhos, negando assim o direito a ter filhos com sangue.

Signaling proteins in spinal parenchyma and dorsal root ganglion in rat with spinal injury-induced spasticity.

Development of progressive muscle spasticity resulting from spinal traumatic injury can be mediated by loss of local segmental inhibition and/or by an increased sensory afferent drive with resulting exacerbated α-motoneuron activity. To identify potential contributions of neuroactive substances in the development of such spasticity state, we employed a well-defined spinal injury-evoked spasticity rat model. Signaling molecules were analyzed in the spinal parenchyma below the level of spinal injury and in the corresponding dorsal root ganglion cells using Kinex™ antibody microarrays. The results uncovered the involvement of angiogenesis and neurodegeneration pathways together with direct cross-talk mediated by several hub proteins with SH-2 domains. At 2 and 5weeks after transection, up-regulation of several proteins including CaMKIV, RONα and PKCδ as well as MAPK3/ERK1 phosphorylation was observed in the spinal ventral horns. Our results indicate that these signaling molecules and their neuronal effector systems cannot only play an important role in the initiation but also in the maintenance of spasticity states after spinal trauma. The exclusivity of specific protein changes observed in lumbar spinal parenchyma but not in dorsal root ganglia indicates that new treatment strategies should primarily target specific spinal segments to prevent or attenuate spasticity states. BIOLOGICAL SIGNIFICANCE: Development of progressive muscle spasticity and rigidity represents a serious complication associated with spinal ischemic or traumatic injury. Signaling proteins, including their phosphorylation status, were analyzed in the spinal parenchyma below the level of spinal injury and in the corresponding dorsal root ganglion cells in a rat model of spinal injury using Kinex™ antibody microarrays. The results uncovered direct protein interaction mediated cross-talk between angiogenesis and neurodegeneration pathways, which may significantly contribute to the healing process in the damaged region. Importantly, we identified several target proteins exclusively observed in the spinal lumbar ventral horns, where such proteins may not only play an important role in the initiation but also in the maintenance of spasticity states after spinal trauma. Hence, potential new treatment strategies such as gene silencing or drug treatment should primarily target spinal parenchymal sites at and around the injury epicenter and most likely employ intrathecal or targeted spinal segment-specific vector or drug delivery. We believe that this work will stimulate future translational research, ultimately leading to the improvement of quality of life of patients with spinal traumatic injury.

Human neural stem cell replacement therapy for amyotrophic lateral sclerosis by spinal transplantation.

BACKGROUND: Mutation in the ubiquitously expressed cytoplasmic superoxide dismutase (SOD1) causes an inherited form of Amyotrophic Lateral Sclerosis (ALS). Mutant synthesis in motor neurons drives disease onset and early disease progression. Previous experimental studies have shown that spinal grafting of human fetal spinal neural stem cells (hNSCs) into the lumbar spinal cord of SOD1(G93A) rats leads to a moderate therapeutical effect as evidenced by local α-motoneuron sparing and extension of lifespan. The aim of the present study was to analyze the degree of therapeutical effect of hNSCs once grafted into the lumbar spinal ventral horn in presymptomatic immunosuppressed SOD1(G93A) rats and to assess the presence and functional integrity of the descending motor system in symptomatic SOD1(G93A) animals. METHODS/PRINCIPAL FINDINGS: Presymptomatic SOD1(G93A) rats (60-65 days old) received spinal lumbar injections of hNSCs. After cell grafting, disease onset, disease progression and lifespan were analyzed. In separate symptomatic SOD1(G93A) rats, the presence and functional conductivity of descending motor tracts (corticospinal and rubrospinal) was analyzed by spinal surface recording electrodes after electrical stimulation of the motor cortex. Silver impregnation of lumbar spinal cord sections and descending motor axon counting in plastic spinal cord sections were used to validate morphologically the integrity of descending motor tracts. Grafting of hNSCs into the lumbar spinal cord of SOD1(G93A) rats protected α-motoneurons in the vicinity of grafted cells, provided transient functional improvement, but offered no protection to α-motoneuron pools distant from grafted lumbar segments. Analysis of motor-evoked potentials recorded from the thoracic spinal cord of symptomatic SOD1(G93A) rats showed a near complete loss of descending motor tract conduction, corresponding to a significant (50-65%) loss of large caliber descending motor axons. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that in order to achieve a more clinically-adequate treatment, cell-replacement/gene therapy strategies will likely require both spinal and supraspinal targets.

Chronic spinal compression model in minipigs: a systematic behavioral, qualitative, and quantitative neuropathological study.

The goal of the present study was to develop a porcine spinal cord injury (SCI) model, and to describe the neurological outcome and characterize the corresponding quantitative and qualitative histological changes at 4-9 months after injury. Adult Gottingen-Minnesota minipigs were anesthetized and placed in a spine immobilization frame. The exposed T12 spinal segment was compressed in a dorso-ventral direction using a 5-mm-diameter circular bar with a progressively increasing peak force (1.5, 2.0, or 2.5 kg) at a velocity of 3 cm/sec. During recovery, motor and sensory function were periodically monitored. After survival, the animals were perfusion fixed and the extent of local SCI was analyzed by (1) post-mortem MRI analysis of dissected spinal cords, (2) qualitative and quantitative analysis of axonal survival at the epicenter of injury, and (3) defining the presence of local inflammatory changes, astrocytosis, and schwannosis. Following 2.5-kg spinal cord compression the animals demonstrated a near complete loss of motor and sensory function with no recovery over the next 4-9 months. Those that underwent spinal cord compression with 2 kg force developed an incomplete injury with progressive partial neurological recovery characterized by a restricted ability to stand and walk. Animals injured with a spinal compression force of 1.5 kg showed near normal ambulation 10 days after injury. In fully paralyzed animals (2.5 kg), MRI analysis demonstrated a loss of spinal white matter integrity and extensive septal cavitations. A significant correlation between the magnitude of loss of small and medium-sized myelinated axons in the ventral funiculus and neurological deficits was identified. These data, demonstrating stable neurological deficits in severely injured animals, similarities of spinal pathology to humans, and relatively good post-injury tolerance of this strain of minipigs to spinal trauma, suggest that this model can successfully be used to study therapeutic interventions targeting both acute and chronic stages of SCI.

The ROCK inhibitor Y-27632 improves recovery of human embryonic stem cells after fluorescence-activated cell sorting with multiple cell surface markers.

BACKGROUND: Due to the inherent sensitivity of human embryonic stem cells (hESCs) to manipulations, the recovery and survival of hESCs after fluorescence-activated cell sorting (FACS) can be low. Additionally, a well characterized and robust methodology for performing FACS on hESCs using multiple-cell surface markers has not been described. The p160-Rho-associated coiled kinase (ROCK) inhibitor, Y-27632, previously has been identified as enhancing survival of hESCs upon single-cell dissociation, as well as enhancing recovery from cryopreservation. Here we examined the application of Y-27632 to hESCs after FACS to improve survival in both feeder-dependent and feeder-independent growth conditions. METHODOLOGY/PRINCIPAL FINDINGS: HESCs were sorted using markers for SSEA-3, TRA-1-81, and SSEA-1. Cells were plated after sorting for 24 hours in either the presence or the absence of Y-27632. In both feeder-dependent and feeder-independent conditions, cell survival was greater when Y-27632 was applied to the hESCs after sort. Specifically, treatment of cells with Y-27632 improved post-sort recovery up to four fold. To determine the long-term effects of sorting with and without the application of Y-27632, hESCs were further analyzed. Specifically, hESCs sorted with and without the addition of Y-27632 retained normal morphology, expressed hESC-specific markers as measured by immunocytochemistry and flow cytometry, and maintained a stable karyotype. In addition, the hESCs could differentiate into three germ layers in vitro and in vivo in both feeder-dependent and feeder-independent growth conditions. CONCLUSIONS/SIGNIFICANCE: The application of Y-27632 to hESCs after cell sorting improves cell recovery with no observed effect on pluripotency, and enables the consistent recovery of hESCs by FACS using multiple surface markers. This improved methodology for cell sorting of hESCs will aid many applications such as removal of hESCs from secondary cell types, identification and isolation of stem cell subpopulations, and generation of single cell clones. Finally, these results demonstrate an additional application of ROCK inhibition to hESC research.

Analysis of dosing regimen and reproducibility of intraspinal grafting of human spinal stem cells in immunosuppressed minipigs.

In recent studies using a rat aortic balloon occlusion model, we have demonstrated that spinal grafting of rat or human neuronal precursors or human postmitotic hNT neurons leads to progressive amelioration of spasticity and rigidity and corresponding improvement in ambulatory function. In the present study, we characterized the optimal dosing regimen and safety profile of human spinal stem cells (HSSC) when grafted into the lumbar spinal cord segments of naive immunosuppressed minipigs. Gottingen-Minnesota minipigs (18-23 kg) were anesthetized with halothane, mounted into a spine-immobilization apparatus, and received five bilateral injections of HSSC delivered in 2, 4, 6, 8, or 10 µl of media targeted into L2-L5 central gray matter (lamina VII). The total number of delivered cells ranged between 2,500 and 100,000 per injection. Animals were immunosuppressed with Prograf® for the duration of study. After cell grafting, ambulatory function was monitored daily using a Tarlov's score. Sensory functions were assessed by mechanically evoked skin twitch test. Animals survived for 6-7 weeks. Three days before sacrifice animals received daily injections of bromodeoxyuridine (100 mg/kg; IV) and were then transcardially perfused with 4% paraformaldehyde. Th12-L6 spinal column was then dissected; the spinal cord was removed and scanned with MRI. Lumbar transverse spinal cord sections were then cut and stained with a combination of human-specific (hNUMA, hMOC, hNSE, hSYN) or nonspecific (DCX, MAP2, GABA, CHAT) antibodies. The total number of surviving cells was estimated using stereological quantification. During the first 12-24 h after cell grafting, a modest motor weakness was observed in three of eight animals but was no longer present at 4 days to 7 weeks. No sensory dysfunction was seen at any time point. Postmortem MRI scans revealed the presence of the individual grafts in the targeted spinal cord areas. Histological examination of spinal cord sections revealed the presence of hNUMA-immunoreactive grafted cells distributed between the base of the dorsal horn and the ventral horn. In all grafts intense hMOC, DCX, and hSYN immunoreactivity in grafted cells was seen. In addition, a rich axodendritic network of DCX-positive processes was identified extending 300-700 µm from the grafts. On average, 45% of hNUMA-positive neurons were GABA immunoreactive. Stereological analysis of hNUMA-positive cells showed an average of 2.5- to 3-fold increase in number of surviving cells compared with the number of injected cells. Analysis of spinal structural morphology showed that in animals injected with more than 50,000 cells/injection or volumes of injectate higher than 6 µl/injection there was tissue expansion and disruption of the local axodendritic network. Based on these data the safe total number of injected cells and volume of injectate were determined to be 30,000 cells delivered in ≤6 µl of media. These data demonstrate that highly reproducible delivery of a potential cell therapeutic candidate into spinal parenchyma can be achieved across a wide range of cell doses by direct intraspinal injections. The resulting grafts uniformly showed robust cell survival and progressive neuronal maturation.

Infectious complications and immunodeficiency in patients with human T-cell lymphotropic virus I-associated adult T-cell leukemia/lymphoma.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature T-cells occurring in patients infected with the human T-cell lymphotropic virus-I. These patients frequently develop a variety of infections throughout their disease course. METHODS: Charts and autopsy reports were reviewed for 41 patients with ATL with follow-up varying from 2 to 120 months. Infectious episodes were identified and documented. Analyses of humoral and cell-mediated immunity were performed. Cell-mediated immunity was assessed in vivo with the Merieux multitest skin test panel. Humoral immunity was assessed by quantitative immunoglobulin levels, by determining human antimouse antibody after murine monoclonal antibody infusion and by an in vitro immunoglobulin biosynthesis coculture system. RESULTS: A total of 112 infectious episodes were documented. Fifty-seven serious infections were identified. The incidence of total infections was 1.40/patient-year and for serious infections was 0.71/patient-year. The mean serum IgG and IgA levels were within normal range, the mean IgM level was at the lower limit of normal. Peripheral blood mononuclear cells from all patients studied failed to make meaningful amounts of IgG, M, or A when activated. Peripheral blood mononuclear cells of all of the 13 patients studied suppressed production of immunoglobulin by cocultured normal PBMC. Twenty-three of the 27 patients tested were anergic. CONCLUSIONS: ATL is a profoundly immunosuppressing malignancy. This is manifested by an extremely high incidence of infectious episodes/patient-year. The incidence of infection appears to be greater than for mycosis fungoides, Hodgkin's lymphoma and non-Hodgkin's lymphoma.

Epidemic neuropathy in Cuba: morphological characterization of peripheral nerve lesions in sural nerve biopsies.

More than 50,000 patients were affected in Cuba during an epidemic outbreak of peripheral neuropathy from January 1992 until September 1993. The disease presented as either a retrobulbar optic neuropathy, a predominantly sensory peripheral neuropathy, a dorsolateral myeloneuropathy, or as mixed forms. The morphological findings in sural nerve biopsies from 34 patients with various forms of the disease are presented here. Frozen, paraffin and semi-thin sections were prepared for light and electron microscopy, immunohistochemistry and morphometric analysis. Every case presented morphological alterations ranging from mild axonal dystrophy (9 cases, or 27%) to moderate and severe axonal damage (25 cases, or 73%). In 6 cases (18%), axonal damage was accompanied by perineural fibrosis and vascular abnormalities. Axonal regeneration was noted in 8 cases (23%) and remyelination in 9 (26%). Morphometric analysis showed a predominant loss of myelinated fibers in 92% of the patients. Quantification of myelinated fiber loss in 11 patients revealed a remarkable decrease in large caliber fibers. Scarce mononuclear cells were observed in 17 cases. No virus-like elements were seen. The morphological features found in this study indicate that, regardless of the clinical presentation, peripheral nerve lesions of the epidemic neuropathy in Cuba correspond to an axonal neuropathy. These lesions are compatible with nutritional, toxic, or metabolic etiologies. An inflammatory etiology would be unusual with these lesions.

Adult T-cell leukemia/lymphoma: a working point-score classification for epidemiological studies.

Adult T-cell leukemia/lymphoma (ATL) is a malignancy that occurs most frequently in south-western Japan and the Caribbean basin. The primary etiologic agent for this disease, human T-lymphotropic virus type I (HTLV-I), is endemic in these areas. Only a small percentage of individuals infected with HTLV-I develop ATL. The factors that determine the development of malignant disease as an outcome of HTLV-I infection in an individual are unknown. ATL is histopathologically heterogeneous and firm diagnosis is made on the contribution of clinical, laboratory and histopathologic features. The wide variety of laboratory assays available to geographically diverse populations has led to a need to standardize the criteria for determining the diagnosis of this disease for epidemiologic studies. This report summarizes current information regarding ATL and proposes a classification facilitating comparison of case series in geographically and ethnically different populations.

Human T-lymphotropic virus type I DNA in spinal cord of tropical spastic paraparesis with concomitant human T-lymphotropic virus type I-negative Hodgkin's disease.

We studied a 58-year-old black woman from Barbados who simultaneously developed myelopathy and lymphoma with human T-lymphotropic virus type I (HTLV-I) antibodies in serum and cerebrospinal fluid and died 3 years after onset. Neuropathological examination showed typical tropical spastic paraparesis (TSP). The polymerase chain reaction (PCR) demonstrated defective proviral genome retaining the HTLV-I pX and env regions in thoracic spinal cord, the level most severely affected. Defective HTLV-I in the nervous system retaining the pX region may be relevant to pathogenesis because circulating CD8+ cytotoxic lymphocytes specific for HTLV-I pX occur in HTLV-I myelopathy. This patient's lymph node biopsy specimen was consistent with Hodgkin's disease (HD), nodular sclerosis subtype, of B-cell origin. The PCR in the paraffin-embedded lymph node involved by HD failed to amplify HTLV-I proviral sequences. Complete HTLV-I proviral amplification was obtained in paraffin-embedded lymph nodes form positive controls (adult T-cell leukemia). To our knowledge the association of TSP and HD has not been reported previously. Despite claims that HD may be associated with HTLV-I, we demonstrated absence of HTLV-I-infected T cells in the lymphoid infiltrate of HD in this case, positive HTLV-I serology notwithstanding.

Human T-lymphotropic virus type I DNA in spinal cord of tropical spastic paraparesis with concomitant human T-lymphotropic virus type I negative Hodgkin's disease

We studied a 58 year old black women from Barbados who simultaneously developed myelopathy and lymphoma with human T-lymphotropic virus type I (HTLV-I) antibodies in serum and cerebrospinal fluid and died 3 years after onset. Neuropathological examination showed typical tropical spastic paraparesis (TSP). The polymerase chain reaction (PCR) demonstrated defective proviral genome retaining the HTLV-I pX and env regions in thoracic spinal cord, the level most severely affected. Defective HTLV-I in the nervous system retaining the pX region may be relevant to pathogenesis because circulating CD8+ cytotoxic lymphocytes specific for HTLV-I pX occur in HTLV-I myelopathy. This patient's lymph node biopsy specimen was consistent with Hodgkin's disease (HD), nodular sclerosis subtype, of B-cell origin. The PCR in the paraffin-embedded lymph node involved by HD failed to amplify HTLV-I proviral sequences. Complete HTLV-I proviral amplification was obtained in paraffin-embedded lymph node form positive controls (adults T-cells leukemia). To our knowledge the association of TSP and HD has not been reported previously. Despite claims the HD may be associated with HTLV-I, we demonstrated absence of HTLV-I infected T-cell in the lymphoid infiltrate of HD in this case, positive HTLV-I serology notwithstanding.(AU)

Malignant lymphomas of B-cell lineage with marked tissue eosinophilia. A report of five cases.

Tissue eosinophilia is commonly seen in Hodgkin's disease and non-Hodgkin's lymphomas of T-cell lineage. In contrast, eosinophilia is infrequent in non-Hodgkin's lymphomas of B-cell origin. We describe five-B-cell lymphomas with exuberant tissue eosinophils. According to the Working Formulation, three were classified as large-cell immunoblastic, one as small lymphocytic lymphoma/chronic lymphocytic leukemia, and one as low-grade, not further subclassified, with features of monocytoid B-cell lymphoma. Immunophenotypic studies in each case revealed B-cell lineage; neoplastic cells expressed monotypic immunoglobulin light chain (four of five cases) or pan-B-cell antigens (five of five cases) and were negative for T-cell antigens. Southern blot hybridization in one case revealed immunoglobulin gene rearrangements, further confirming B-cell lineage. Eosinophilopoiesis is stimulated by interleukin 5 (IL-5), and Epstein-Barr virus (EBV) has been shown to upregulate IL-5 production. Therefore, both EBV infection and IL-5 expression were investigated as possibly pathogenetic mechanisms for the eosinophilia. However, both in situ hybridization studies for EBV mRNA and IL-5 mRNA were negative in the neoplastic cells. In one tumor, IL-5 was abundant in the cytoplasm of the eosinophils, a pattern similar to that seen in five cases of Hodgkin's disease studied with the same technique. Although rare, marked tissue eosinophilia may be associated with B-cell non-Hodgkin's lymphomas. Immunophenotypic or molecular genetic analyses are needed to make the correct diagnosis.

Natural history of spinal cord infarction caused by nucleus pulposus embolism.

Nucleus pulposus embolism causing spinal cord infarction is exceptional. A 16-year-old girl was seen with sudden onset of interscapular pain and paraplegia from fatal ischemic transverse myelopathy due to arterial and venous occlusions by fibrocartilaginous embolism. In 32 cases of nucleus pulposus embolism, females predominated (69%) and age distribution was bimodal with peaks at 22 and 60 years (median, 38.5). Embolization was either arterial and venous (50%) or purely arterial (50%). Myelopathy predominated in cervical (69%) and lumbosacral (22%) segments. Schmorl's nodes, larger volume and vascularization of nucleus pulposus in the young, and spinal arteriovenous communications, trauma, and degenerative changes in older patients could be important pathogenetic factors. Diagnosis requires histopathologic confirmation. Nucleus pulposus embolism may be an underlying cause in cases diagnosed as transverse myelitis and ischemic infarction of spinal cord.

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue arising in the kidney.

We describe a malignant lymphoma arising in the kidney that exhibited clinical and histologic features of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Clinically, the neoplasm involved the kidney and one perirenal lymph node (stage IIE) and did not recur or disseminate following nephrectomy, lymphadenectomy, and local radiation therapy. Histologically, the neoplasm recapitulated the features of low-grade B-cell lymphomas of MALT at other sites. The neoplastic cells resembled centrocyte-like cells, some of which formed lymphoepithelial lesions with renal tubules, and reactive lymphoid follicles were scattered within the neoplasm. The neoplastic cells expressed monotypic cytoplasmic Ig kappa. Low-grade B-cell MALT lymphomas arising in the kidney are rare. Their occurrence further demonstrates the diversity of anatomical sites that may be involved by MALT lymphomas. In addition, this neoplasm also had histologic and cytologic features resembling those of monocytoid B-cell lymphoma, supporting the hypothesis that low-grade B-cell lymphomas of MALT and monocytoid B-cell lymphomas are closely related and may be two morphological manifestations of the same neoplasm.

Acute ischemic stroke from fibrocartilaginous embolism to the middle cerebral artery.

BACKGROUND AND PURPOSE: Fibrocartilaginous embolism from the nucleus pulposus has been reported as a rare cause of spinal cord ischemia. We were unable to find previous reports of embolism from this source to cerebral arteries. CASE DESCRIPTION: A previously healthy 17-year-old girl fell during a basketball game. Left hemiparesis and unresponsiveness developed followed by signs of right uncal herniation and death over a 3-day period. There was no evidence of neck, head, or spine trauma, and cardiac evaluation was normal. Neuropathological examination showed extensive ischemic infarction of the right middle cerebral artery territory, brain edema, and herniation. Complete embolic occlusion of the right middle cerebral artery by fibrocartilaginous material, consistent with nucleus pulposus, was documented. Small, terminal coronary artery branches also showed embolism by the same material and limited areas of myocardial infarction. CONCLUSIONS: Acute cerebral embolism after minor trauma in a young patient may be rarely due to fibrocartilaginous embolism from the nucleus pulposus. The pathogenesis of this problem remains poorly understood, but systemic embolism appeared to have occurred in this case.